@article {1515231, title = {A single genetic locus lengthens deer mouse burrows via motor pattern evolution}, journal = {bioRxiv 2023.07.03.547545}, year = {In Preparation}, author = {Harringmeyer, O.S. and C.K. Hu and H.C. Metz and E.L. Mihelic and C. Rosher and J. Sanguinetti-Scheck and H.E. Hoekstra} } @article {1515226, title = {The neural basis of defensive behaviour evolution in Peromyscus mice}, journal = {bioRxiv 2023.07.04.547734}, year = {In Preparation}, author = {Baier, F and K. Reinhard and V. Tong and J. Murmann and K. Farrow and H.E. Hoekstra} } @article {1426058, title = {Adaptive tail-length evolution in deer mice is associated with differential Hoxd13 expression in early development}, journal = {bioRxiv }, year = {Forthcoming}, month = {2021}, abstract = {SUMMARY
Variation in the size and number of axial segments underlies much of the diversity in
animal body plans. Here, we investigate the evolutionary, genetic, and developmental
mechanisms driving tail-length differences between forest and prairie ecotypes of deer mice
(Peromyscus maniculatus). We first show that long-tailed forest mice perform better in an
arboreal locomotion assay, consistent with tails being important for balance during climbing. The
long tails of these forest mice consist of both longer and more caudal vertebrae than prairie mice.
Using quantitative genetics, we identify six genomic regions that contribute to differences in
total tail length, three of which associate with vertebra length and the other three with vertebra
number. For all six loci, the forest allele increases tail length, consistent with the cumulative
effect of natural selection. Two of the genomic regions associated with variation in vertebra
number contain Hox gene clusters. Of those, we find an allele-specific decrease in Hoxd13
expression in the embryonic tail bud of long-tailed forest mice, consistent with its role in axial
elongation. Additionally, we find that forest embryos have more presomitic mesoderm than
prairie embryos, and that this correlates with an increase in the number of neuromesodermal
progenitors (NMPs), which are modulated by Hox13 paralogs. Together, these results suggest a
role for Hoxd13 in the development of natural variation in adaptive morphology on a
microevolutionary timescale.}, author = {Kingsley, E. P. and E.R. Hager and J-M. Lassance and K.M. Tuner and O.S. Harringmeyer and Kirby, C. and B.I. Neugebroen and Hoekstra, H. E.} } @article {1419662, title = {Automated tracking reveals the social network of beach mice and their burrows}, journal = {bioRxiv}, year = {Forthcoming}, month = {2022}, author = {Bedford, N.L. and J.T. Gable and Hu, C.K. and T.B. Wooldridge and N.A. Sokolov, and Lassance, J.M. and Hoekstra, H. E.} } @article {1556451, title = {Evolution of gene expression across brain regions in behaviourally divergent deer mice}, journal = {Molecular Ecology}, year = {2024}, abstract = {The evolution of innate behaviours is ultimately due to genetic variation likely acting in the nervous system. Gene regulation may be particularly important because it can evolve in a modular brain-region specific fashion through the concerted action of cis- and trans-regulatory changes. Here, to investigate transcriptional variation and its regulatory basis across the brain, we perform RNA sequencing (RNA-Seq) on ten brain subregions in two sister species of deer mice (Peromyscus maniculatus and P. polionotus){\textemdash}which differ in a range of innate behaviours, including their social system{\textemdash}and their F1 hybrids. We find that most of the variation in gene expression distinguishes subregions, followed by species. Interspecific differential expression (DE) is pervasive (52{\textendash}59\% of expressed genes), whereas the number of DE genes between sexes is modest overall (~3\%). Interestingly, the identity of DE genes varies considerably across brain regions. Much of this modularity is due to cis-regulatory divergence, and while 43\% of genes were consistently assigned to the same gene regulatory class across subregions (e.g. conserved, cis- or trans-regulatory divergence), a similar number were assigned to two or more different gene regulatory classes. Together, these results highlight the modularity of gene expression differences and divergence in the brain, which may be key to explain how the evolution of brain gene expression can contribute to the astonishing diversity of animal behaviours.}, author = {Andreas F. Kautt and Jenny Chen and Caitlin L. Lewarch and Caroline Hu and Kyle Turner and Jean-Marc Lassance and Felix Baier and Nicole L. Bedford and Andres Bendesky and Hopi E. Hoekstra} } @article {1458991, title = {Two pup vocalization types are genetically and functionally separable in deer mice.}, journal = {Current Biology}, volume = {33}, year = {2023}, month = {2022}, pages = {1237-1248.e4}, author = {Jourjine, N. and M.L. Woolfolk and J.I. Sanguinetti-Scheck and J.E. Sabatini and S. McFadden and A.K. Lindholm and H.E. Hoekstra} } @article {1458986, title = {Transposable element competition shapes the deer mouse genome.}, journal = {Molecular Biology and Evolution}, volume = {40}, year = {2023}, month = {2022}, pages = {msad069}, author = {Gozashti, L. and C. Feschotte and H.E. Hoekstra} } @journal {1458981, title = {Post-mating parental behavior trajectories differ across four species of deer mice.}, volume = {17}, year = {2022}, pages = {e0276052}, abstract = {Among species, parental behaviors vary in their magnitude, onset relative to reproduction, and sexual dimorphism. In deer mice (genus Peromyscus), while most species are promiscuous with low paternal care, monogamy and biparental care have evolved at least twice under different ecological conditions. Here, in a common laboratory setting, we monitored parental behaviors of males and females of two promiscuous (eastern deer mouse P. maniculatus and white-footed mouse P. leucopus) and two monogamous (oldfield mouse P. polionotus and California mouse P. californicus) species from before mating to after giving birth. In the promiscuous species, females showed parental behaviors largely after parturition, while males showed little parental care. In contrast, both sexes of monogamous species performed parental behaviors. However, while oldfield mice began to display parental behaviors before mating, California mice showed robust parental care behaviors only postpartum. These different parental-care trajectories in the two monogamous species align with their socioecology. Oldfield mice have overlapping home ranges with relatives, so infants they encounter, even if not their own, are likely to be closely related. By contrast, California mice disperse longer distances into exclusive territories with possibly unrelated neighbors, decreasing the inclusive fitness benefits of caring for unfamiliar pups before parenthood. Together, we find that patterns of parental behaviors in Peromyscus are consistent with predictions from inclusive fitness theory.}, author = {Khadraoui, M. and J.R. Merritt and H.E. Hoekstra and A. Bendesky} } @article {1440279, title = {Massive inversion polymorphisms shape the genomic landscape of deer mice}, journal = {Nature Ecology \& Evolution}, volume = {6}, year = {2022}, pages = {1965{\textendash}1979}, abstract = {Chromosomal inversions are an important form of structural variation that can affect recombination, chromosome structure and fitness. However, because inversions can be challenging to detect, the prevalence and hence the significance of inversions segregating within species remains largely unknown, especially in natural populations of mammals. Here, by combining population-genomic and long-read sequencing analyses in a single, widespread species of deer mouse (Peromyscus maniculatus), we identified 21 polymorphic inversions that are large (1.5{\textendash}43.8 Mb) and cause near-complete suppression of recombination when heterozygous (0{\textendash}0.03 cM Mb-1). We found that inversion breakpoints frequently occur in centromeric and telomeric regions and are often flanked by long inverted repeats (0.5{\textendash}50 kb), suggesting that they probably arose via ectopic recombination. By genotyping inversions in populations across the species{\textquoteright} range, we found that the inversions are often widespread and do not harbour deleterious mutational loads, and many are likely to be maintained as polymorphisms by divergent selection. Comparisons of forest and prairie ecotypes of deer mice revealed 13 inversions that contribute to differentiation between populations, of which five exhibit significant associations with traits implicated in local adaptation. Taken together, these results show that inversion polymorphisms have a significant impact on recombination, genome structure and genetic diversity in deer mice and likely facilitate local adaptation across the widespread range of this species.}, author = {Olivia S. Harringmeyer and Hopi E. Hoekstra} } @article {1440188, title = {Gregor Johann Mendel and the development of modern evolutionary biology}, journal = {PNAS}, volume = {119}, year = {2022}, pages = {e2201327119}, author = {Nils Chr. Stenseth and Leif Andersson and Hopi E. Hoekstra} } @article {1440187, title = {Behavioral genetics and genomics: Mendel{\textquoteright}s peas, mice,and bees}, journal = {PNAS}, volume = {119}, year = {2022}, pages = {e21221541119}, abstract = {The question of the heritability of behavior has been of long fascination to scientists and the broader public. It is now widely accepted that most behavioral variation has a genetic component, although the degree of genetic in fl u- ence differs widely across behaviors. Starting with Men- del {\textquoteright} s remarkable discovery of {\textquotedblleft} inheritance factors, {\textquotedblright} it has become increasingly clear that speci fi c genetic variants that in fl uence behavior can be identi fi ed. This goal is not without its challenges: Unlike pea morphology, most natu- ral behavioral variation has a complex genetic architec- ture. However, we can now apply powerful genome-wide approaches to connect variation in DNA to variation in behavior as well as analyses of behaviorally related varia- tion in brain gene expression, which together have pro- vided insights into both the genetic mechanisms underlying behavior and the dynamic relationship between genes and behavior, respectively, in a wide range of species and for a diversity of behaviors. Here, we focus on two systems to illustrate both of these approaches: the genetic basis of bur- rowing in deer mice and transcriptomic analyses of division of labor in honey bees. Finally, we discuss the troubled rela- tionship between the fi eld of behavioral genetics and eugenics, which reminds us that we must be cautious about how we discuss and contextualize the connections between genes and behavior, especially in humans.}, author = {Hopi E. Hoekstra and Robinson, Gene E.} } @article {1440024, title = {Interspecific variation in cooperative burrowing behavior by Peromyscus mice}, journal = {Evolution Letters}, volume = {https://doi.org/10.1002/evl3.293}, year = {2022}, abstract = {Animals often adjust their behavior according to social context, but the capacity for such behavioral flexibility can vary among species. Here, we test for interspecific variation in behavioral flexibility by comparing burrowing behavior across three species of deer mice (genus Peromyscus) with divergent social systems, ranging from promiscuous (Peromyscus leucopus and Peromyscus maniculatus) to monogamous (Peromyscus polionotus). First, we compared the burrows built by individual mice to those built by pairs of mice in all three species. Although burrow length did not differ in P. leucopus or P. maniculatus, we found that P. polionotus pairs cooperatively constructed burrows that were nearly twice as long as those built by individuals and that opposite-sex pairs dug longer burrows than same-sex pairs. Second, to directly observe cooperative digging behavior in P. polionotus, we designed a burrowing assay in which we could video-record active digging in narrow, transparent enclosures. Using this novel assay, we found, unexpectedly, that neither males nor females spent more time digging with an opposite-sex partner. Rather, we demonstrate that opposite-sex pairs are more socially cohesive and thus more efficient digging partners than same-sex pairs. Together, our study demonstrates how social context can modulate innate behavior and offers insight into how differences in behavioral flexibility may evolve among closely related species.}, author = {Nicole L. Bedford and Jesse N. Weber and Wenfei Tong and Felix Baier and Ariana Kam and Rebecca A. Greenberg and Hopi E. Hoekstra} } @article {1419664, title = {A novel enhancer of Agouti contributes to parallel evolution of cryptically colored beach mice}, journal = {PNAS}, volume = {119}, year = {2022}, month = {2021}, pages = {e220286119}, abstract = {Identifying the genetic basis of repeatedly evolved traits provides a way to reconstruct their evolutionary history and ultimately investigate the predictability of evolution. Here, we focus on the old fi eld mouse ( Peromyscus polionotus ), which occurs in the southeastern United States, where it exhibits considerable color variation. Dorsal coats range from dark brown in mainland mice to near white in mice inhabiting sandy beaches; this light pelage has evolved independently on Florida {\textquoteright} s Gulf and Atlantic coasts as camou fl age from predators. To facilitate genomic analyses, we fi rst generated a chromosome-level genome assembly of Peromyscus polionotus subgriseus . Next, in a uniquely variable mainland population ( Peromyscus polionotus albifrons ), we scored 23 pigment traits and performed targeted resequencing in 168 mice. We fi nd that pigment variation is strongly associated with an \~{} 2-kb region \~{} 5 kb upstream of the Agouti sig- naling protein coding region. Using a reporter-gene assay, we demonstrate that this reg- ulatory region contains an enhancer that drives expression in the dermis of mouse embryos during the establishment of pigment prepatterns. Moreover, extended tracts of homozygosity in this Agouti region indicate that the light allele experienced recent and strong positive selection. Notably, this same light allele appears fi xed in both Gulf and Atlantic coast beach mice, despite these populations being separated by \> 1,000 km. Together, our results suggest that this identi fi ed Agouti enhancer allele has been main- tained in mainland populations as standing genetic variation and from there, has spread to and been selected in two independent beach mouse lineages, thereby facilitating their rapid and parallel evolution.}, author = {Wooldridge, T.B and A.F. Kautt and Lassance, J.M. and S. McFadden and Domingues, V. S. and Mallarino, R. and Hoekstra, H. E.} } @article {1419658, title = {Cis-regulatory changes in locomotor genes are associated with the evolution of burrowing behavior.}, journal = {Cell Reports}, volume = {38}, year = {2022}, month = {2021}, pages = {110360}, abstract = {How evolution modifies complex, innate behaviors is largely unknown. Divergence in many morphological
traits, and some behaviors, is linked to cis-regulatory changes in gene expression. Given this, we compare
brain gene expression of two interfertile sister species of Peromyscus mice that show large and heritable differences
in burrowing behavior. Species-level differential expression and allele-specific expression in F1 hybrids
indicate a preponderance of cis-regulatory divergence, including many genes whose cis-regulation is
affected by burrowing behavior. Genes related to locomotor coordination show the strongest signals of
lineage-specific selection on burrowing-induced cis-regulatory changes. Furthermore, genetic markers
closest to these candidate genes associate with variation in burrow shape in a genetic cross, suggesting
an enrichment for loci affecting burrowing behavior near these candidate locomotor genes. Our results provide
insight into how cis-regulated gene expression can depend on behavioral context and how this dynamic
regulatory divergence between species may contribute to behavioral evolution.}, author = {Hu, C.K. and R.A. York and Metz, H. C. and Bedford, N.L. and H.B. Fraser and Hoekstra, H. E.} } @article {1393174, title = {A chromosomal inversion contributes to divergence in multiple traits between deer mouse ecotypes}, journal = {Science}, volume = {377 }, year = {2022}, pages = {399-405}, abstract = {How locally adapted ecotypes are established and maintained within a species is a long-standing question in evolutionary biology. Using forest and prairie ecotypes of deer mice (Peromyscus maniculatus), we characterized the genetic basis of variation in two defining traits{\textemdash}tail length and coat color{\textemdash}and discovered a 41-megabase chromosomal inversion linked to both. The inversion frequency is 90\% in the dark, long-tailed forest ecotype; decreases across a habitat transition; and is absent from the light, short-tailed prairie ecotype. We implicate divergent selection in maintaining the inversion at frequencies observed in the wild, despite high levels of gene flow, and explore fitness benefits that arise from suppressed recombination within the inversion. We uncover a key role for a large, previously uncharacterized inversion in the evolution and maintenance of classic mammalian ecotypes.}, author = {Emily R Hager and Olivia S. Harringmeyer and T. Brock Wooldridge and Shunn Theingi and Jacob T. Gable and Sade McFadden and Beverly Neugeboren and Kyle M. Turner and Hopi E. Hoekstra} } @article {1397676, title = {Tail length evolution in deer mice: linking morphology, behavior and function.}, journal = {Integrative and Comparative Zoology}, volume = {61}, year = {2021}, month = {in press}, abstract = {

Determining how variation in morphology affects animal performance (and ultimately fitness) is key to understanding the complete process of evolutionary adaptation. Long tails have evolved many times in arboreal and semi-arboreal rodents; in deer mice, long tails have evolved repeatedly in populations occupying forested habit even within a single species (Peromyscus maniculatus). Here we use a combination of functional modeling, laboratory studies, and museum records to test hypotheses about the function of tail-length variation in deer mice. First, we use computational models, informed by museum records documenting natural variation in tail length, to test whether differences in tail morphology between forest and prairie subspecies can influence performance in behavioral contexts relevant for tail use. We find that the deer mouse tail plays little role in statically adjusting center of mass or in correcting body pitch and yaw, but rather it can affect body roll during arboreal locomotion. In this context, we find that even intraspecific tail-length variation could result in substantial differences in how much body rotation results from equivalent tail motions (i.e., tail effectiveness), but the relationship between commonly-used metrics of tail-length variation and effectiveness is non-linear. We further test whether caudal vertebra length, number, and shape are associated with differences in how much the tail can bend to curve around narrow substrates (i.e., tail curvature) and find that, as predicted, the shape of the caudal vertebrae is associated with intervertebral bending angle across taxa. However, although forest and prairie mice typically differ in both the length and number of caudal vertebrae, we do not find evidence that this pattern is the result of a functional trade-off related to tail curvature. Together, these results highlight how even simple models can both generate and exclude hypotheses about the functional consequences of trait variation for organismal-level performance.

}, author = {Emily R. Hager and Hopi E. Hoekstra} } @article {1391807, title = {Expanding evolutionary neuroscience: insights from comparing variation in behavior}, journal = {Neuron}, volume = {2}, year = {2021}, pages = {1084-1099}, abstract = {Neuroscientists have long studied species with convenient biological features to discover how behavior emerges from conserved molecular, neural, and circuit level processes. With the advent of new tools, from viral vectors and gene editing to automated behavioral analyses, there has been a recent wave of interest in developing new, {\textquotedblleft}nontraditional{\textquotedblright} model species. Here, we advocate for a complementary approach to model species development, that is, model clade development, as a way to integrate an evolutionary comparative approach with neurobiological and behavioral experiments. Capitalizing on natural behavioral variation in and investing in experimental tools for model clades will be a valuable strategy for the next generation of neuroscience discovery.}, author = {Jourjine, Nicholas and Hopi E. Hoekstra} } @article {1391793, title = {Fishing for the genetic basis of migratory behavior}, journal = {Cell}, volume = {184}, year = {2021}, pages = {303-305}, abstract = {For many species, migrating at just the right time is essential for both survival and reproduction. A new study in salmon localizes a small genomic region associated with migration timing, which in turn affects other physiological traits, suggesting that a seemingly complex suite of migration traits is linked by one {\textquotedblleft}simple{\textquotedblright} phenotype.}, author = {Harringmeyer, Olivia S and Woolfolk, Maya L and Hopi E. Hoekstra} } @article {1230834, title = {The Tug1 locus is essential for male fertility}, journal = {Genome Biol.}, volume = {21}, year = {2020}, pages = {237}, abstract = {Several long noncoding RNAs (lncRNAs) have been shown to function as central components of molecular machines that play fundamental roles in biology. While the number of annotated lncRNAs in mammalian genomes has greatly expanded, their functions remain largely uncharacterized. This is compounded by the fact that identifying lncRNA loci that have robust and reproducible phenotypes when mutated has been a challenge. We previously generated a cohort of 20 lncRNA loci knockout mice. Here, we extend our initial study and provide a more detailed analysis of the highly conserved lncRNA locus, Taurine Upregulated Gene 1 (Tug1). We report that Tug1 knockout male mice are sterile with complete penetrance due to a low sperm count and abnormal sperm morphology. Having identified a lncRNA loci with a robust phenotype, we wanted to determine which, if any, potential elements contained in the Tug1 genomic region (DNA, RNA, protein, or the act of transcription) have activity. Using engineered mouse models and cell-based assays, we provide evidence that the Tug1 locus harbors three distinct regulatory activities - two noncoding and one coding: (i) a cis DNA repressor that regulates many neighboring genes, (ii) a lncRNA that can regulate genes by a trans-based function, and finally (iii) Tug1 encodes an evolutionary conserved peptide that when overexpressed impacts mitochondrial membrane potential. Our results reveal an essential role for the Tug1 locus in male fertility and uncover three distinct regulatory activities in the Tug1 locus, thus highlighting the complexity present at lncRNA loci.}, author = {Lewandowski, J.P. and Dumbovi{\'c}, G. and Watson, A.R. and Hwang, T. and E. Jacobs-Palmer and Chang, N. and Much, C. and Turner, K. and Kirby, C. and Schulz, J.F. and Muller, C-L. and Rubenstein, N.D. and Groff, A.F. and Liapis, S.C. and Gerhardinger, C. and Hubner, N. and van Heesch, S. and Hoekstra, H. E. and Sauvageau, M. and Rinn, J.L.} } @article {1156279, title = {Linking a mutation to survival in wild mice.}, journal = {Science}, volume = {363}, year = {2019}, pages = {499-504}, abstract = {Adaptive evolution in novel or changing environments can be difficult to predict because the functional connections between genotype, phenotype, and fitness are complex. Here, we make these explicit connections by combining field and laboratory experiments in wild mice. We first directly estimate natural selection on pigmentation traits and an underlying pigment locus, Agouti, using experimental enclosures of mice on different soil colors. Next, we show how a mutation in Agouti associated with survival causes lighter coat color via changes in its protein binding properties. Together, our findings demonstrate how a sequence variant alters phenotype and then reveal the ensuing ecological consequences that drive changes in population allele frequency, thereby illuminating the process of evolution by natural selection.}, author = {Barrett, R.D.H. and Laurent, S. and Mallarino, R. and Pfeifer, S.P. and Xu, C.C.Y. and Foll, M. and Wakamatsu, K. and Duke-Cohan, J.S. and Jensen, J. D. and Hoekstra, H. E.} } @article {1143316, title = {The genetics of morphological and behavioral island traits in deer mice}, journal = {Proceedings of the Royal Society B}, volume = {286}, year = {2019}, month = {2019}, pages = {20191697}, abstract = {Animals on islands often exhibit dramatic differences in morphology and behavior compared to mainland individuals, a phenomenon known as the "island syndrome". These differences, such as changes in body size and aggression, are thought to be adaptations to island environments, where there are high resource levels, low predation, limited dispersal, and thus high population densities. However, the extent to which island traits have a genetic basis or instead represent plastic responses to environmental extremes is often unknown. Here, we revisit a classic case of island syndrome in deer mice (Peromyscus maniculatus) from British Columbia. Previous field studies suggested that Saturna Island mice evolved several island traits, including higher body weight and reduced aggression relative to mainland populations. Using historical collections, we show that Saturna Island mice and those from neighboring islands are approximately 35\% (~5g) heavier than mainland mice. We then collected mice from two focal populations: Saturna Island and a nearby mainland population. First, using molecular data, we find that these populations are genetically distinct, having diverged approximately 10 thousand years ago. Second, we established laboratory colonies and find that Saturna Island mice are heavier both because they are longer and have disproportionately more lean mass. These trait differences are maintained in second-generation captive-born mice raised in a common environment, implying a strong heritable component. In addition, island-mainland hybrids are heavier when born to island mothers than to mainland mothers, revealing a maternal genetic effect on body weight. Next, using behavioral testing in the lab, we also find that wild-caught island mice are less aggressive than mainland mice. However, lab-raised mice born to these founders do not differ in aggression, regardless of whether they are tested in conditions that induce low or high aggression, suggesting the large behavioral difference observed between wild-caught island and mainland individuals is likely a plastic response. Together, our results reveal that these mice respond differently to environmental conditions on islands, evolving both heritable changes in a morphological trait and also expressing a plastic phenotypic response in a behavioral trait.}, author = {Baier, F and Hoekstra, HE} } @article {1128634, title = {Diet-based assortative mating through sexual imprinting}, journal = {Ecology \& Evolution}, volume = {00}, year = {2019}, month = {2019}, pages = {1-6}, abstract = {

Speciation is facilitated by {\textquotedblleft}magic traits,{\textquotedblright} where divergent natural selection on such traits also results in assortative mating. In animal populations, diet has the potential to act as a magic trait if populations diverge in consumed food that incidentally affects mating and therefore sexual isolation. While diet-based assortative mating has been observed in the laboratory and in natural populations, the mechanisms causing positive diet-based assortment remain largely unknown. Here, we experimentally created divergent diets in a sexually imprinting species of mouse, Peromyscus gossypinus (the cotton mouse), to test the hypothesis that sexual imprinting on diet could be a mechanism that generates rapid and significant sexual isolation. We provided breeding pairs with novel garlic- or orange-flavored water and assessed whether their offspring, exposed to these flavors in utero and in the nest before weaning, later preferred mates that consumed the same flavored water as their parents. While males showed no preference, females preferred males of their parental diet, which is predicted to yield moderate sexual isolation. Thus, our experiment demonstrates the potential for sexual imprinting on dietary cues learned in utero and/or postnatally to facilitate reproductive isolation and potentially speciation.

}, author = {EK Delaney and Hoekstra, HE} } @article {1143684, title = {The genetic basis of a social polymorphism in halictid bees}, journal = {Nature Communications}, volume = {9}, year = {2018}, pages = {4338}, abstract = {The emergence of eusociality represents a major evolutionary transition from solitary to group reproduction. The most commonly studied eusocial species, honey bees and ants, represent the behavioral extremes of social evolution but lack close relatives that are non-social. Unlike these species, the halictid bee\ Lasioglossum albipes\ produces both solitary and eusocial nests and this intraspecific variation has a genetic basis. Here, we identify genetic variants associated with this polymorphism, including one located in the intron of\ syntaxin 1a (syx1a), a gene that mediates synaptic vesicle release. We show that this variant can alter gene expression in a pattern consistent with differences between social and solitary bees. Surprisingly,\ syx1a\ and several other genes associated with sociality in\ L.\ albipes\ have also been implicated in autism spectrum disorder in humans. Thus, genes underlying behavioral variation in\ L.\ albipes\ may also shape social behaviors across a wide range of taxa, including humans.}, author = {Kocher, Sarah D. and Mallarino, Ricardo and Benjamin E. R. Rubin and Douglas W. Yu and Hopi E. Hoekstra and Naomi E. Pierce} } @article {1128630, title = {Sibling rivalry: Males with more brothers develop larger testes}, journal = {Ecology and Evolution}, volume = {8}, year = {2018}, pages = {8197-8203}, abstract = {When females mate with multiple partners in a reproductive cycle, the relative number of competing sperm from rival males is often the most critical factor in determining paternity. Gamete production is directly related to testis size in most species, and is associated with both mating behavior within a system and perceived risk of competition. Peromyscus maniculatus is naturally promiscuous and males invest significantly more in sperm production than males of P. polionotus, their monogamous sister-species. Here we show that the relatively larger testes in P. maniculatus are retained, even after decades of enforced monogamy in captivity. While these results suggest that differences in sperm production between species with divergent evolutionary histories can be maintained, we also show that the early rearing environment of males can strongly influence their testis size as adults. Using a second-generation hybrid population to increase variation in testis size, we show that males reared in litters with more brothers develop larger testes as adults. Importantly, this difference in testis size is also associated with increased fertility. Together, our findings suggest that sperm production may be both broadly shaped by natural selection over evolutionary timescales and also finely tuned during early development.}, author = {Fisher, H. S. and KA Hook and WD Weber and Hoekstra, HE} } @article {1120549, title = {Quick Guide: African striped mice.}, journal = {Current Biology}, volume = {28}, year = {2018}, pages = {R293{\textendash}R305}, author = {Mallarino, R. and N. Pillay and Hoekstra, H. E. and C. Schradin} } @article {1116164, title = {Divergent genetic mechanisms lead to spiny hair in mammals}, journal = {PLoS ONE}, volume = {13}, year = {2018}, pages = {e0202219}, abstract = {In humans, a single amino acid change (V370A) in the Ecdysoplasin A receptor (Edar) gene is associated with a unique hair phenotype in East Asian populations. Transgenic experiments in mouse show that this mutation enhances Edar signaling in vitro, which in turn alters multiple aspects of hair morphology. Here we tested whether this substitution contributes to the spiny hair observed in six families of rodents. We first measured hair traits, focusing on guard hairs and their physical properties, such as tension and deformation, and compared the morphology between spiny and non-spiny sister lineages. Two distinct hair morphologies were repeatedly observed in spiny rodent lineages: hairs with a grooved cross-section and a second near cylindrical form, which differ in their cross-section shape as well as their tensiometric properties. Next, we sequenced a portion of the Edar locus in these same species. Most species surveyed have the common amino acid valine at position 370, but the kangaroo rat and spiny pocket mouse have an isoleucine. We also found one additional amino acid variant: tree rats have a Leu422Val polymorphism. However, none of these variants are associated with changes in hair morphology. Together these data suggest that the specific Edar mutation associated with variation in human hair morphology does not play a role in modifying hairs in wild rodents, highlighting that different evolutionary pathways can produce similar spiny hair morphology.}, author = {Goncalves, G.L. and Masestri, R. and Moreira, G.R.P. and Jacobi, M.A. M. and Freitas, T.R.O. and Hoekstra, H. E.} } @article {1042201, title = {The evolution of nesting behaviour in Peromyscus mice}, journal = {Animal Behaviour}, volume = {139}, year = {2018}, month = {2018}, pages = {103-115}, abstract = {

Structures built by animals, such as nests, often can be considered extended\ phenotypes\ that facilitate the study of animal behaviour. For rodents, nest building is both an important form of behavioural\ thermoregulation\ and a critical component of\ parental care. Changes in nest structure or the prioritization of\ nesting\ behaviour are therefore likely to have consequences for survival and reproduction, and both biotic and abiotic environmental factors are likely to influence the adaptive value of such differences. Here we first develop a novel assay to investigate interspecific variation in the nesting behaviour of deer mice (genus\ Peromyscus). Using this assay, we find that, while there is some variation in the complexity of the nests built by\ Peromyscus\ mice, differences in the latency to begin nest construction are more striking. Four of the seven taxa examined here build nests within an hour of being given nesting material, but this latency to nest is not related to ultimate differences in nest structure, suggesting that the ability to nest is relatively conserved within the genus, but species differ in their prioritization of nesting behaviour. We also find that latency to nest is not correlated with body size, climate or the construction of burrows that create\ microclimates. However, the four taxa with short nesting latencies all have monogamous\ mating systems, suggesting that differences in nesting latency may be related to social environment. This detailed characterization of nesting behaviour within the genus provides an important foundation for future studies of the genetic and neurobiological mechanisms that contribute to the evolution of behaviour.

}, author = {C. L. Lewarch and Hoekstra, H. E.} } @article {1018676, title = {The evolutionary history of Nebraska deer mice: local adaptation in the face of strong gene flow.}, journal = {Molecular Biology and Evolution}, volume = {35}, year = {2018}, pages = {792-806}, abstract = {The interplay of gene flow, genetic drift, and local selective pressure is a dynamic process that has been well studied from a theoretical perspective over the last century. Wright and Haldane laid the foundation for expectations under an island-continent model, demonstrating that an island specific beneficial allele may be maintained locally if the selection coefficient is larger than the rate of migration of the ancestral allele from the continent. Subsequent extensions of this model have provided considerably more insight into the conditions under which such a beneficial allele may be maintained, lost, or fixed. Yet, connecting theoretical results with empirical data has proven challenging, owing to a lack of information on the relationship between genotype, phenotype, and fitness. Here, we examine the demographic and selective history of deer mice in and around the Nebraska Sand Hills, a system in which variation at the Agouti locus affects cryptic coloration that in turn affects the survival of mice in their local habitat. We first genotyped 250 individuals from eleven sites along a transect spanning the Sand Hills at 670,000 SNPs across the genome. Using these genomic data, we found that deer mice first colonized the Sand Hills following the last glacial period. Subsequent high rates of gene flow have served to homogenize the majority of the genome between populations on and off the Sand Hills, with the exception of the Agouti pigmentation locus. Furthermore, we observe strong haplotype structure around putatively beneficial mutations within the Agouti locus, and these mutations are strongly associated with the pigment traits that are strongly correlated with local soil coloration and thus responsible for cryptic coloration. We discuss these empirical results in light of theoretical expectations, thereby providing a complete example of the dynamics between ancestral gene flow and local adaptation in a classic mammalian system.}, author = {Pfeifer, SP and Laurent, S and Sousa, VC and Linnen, C. R. and Foll, M and Excoffier, L and Hoekstra, HE and Jensen, J. D.} } @article {1018661, title = {Sexual imprinting and speciation in two Peromyscus species.}, journal = {Evolution}, volume = {72}, year = {2018}, month = {2018}, pages = {274{\textendash}287}, abstract = {Sexual isolation, a reproductive barrier, can prevent interbreeding between diverging populations or species. Sexual isolation can have a clear genetic basis; however, it may also result from learned mate preferences that form via sexual imprinting. Here, we demonstrate that two sympatric sister species of mice -- the white-footed mouse (Peromyscus leucopus) and its closest relative, the cotton mouse (P. gossypinus) -- hybridize only rarely in the wild despite co-occurring in the same habitat and lack of any measurable intrinsic postzygotic barriers in laboratory crosses. We present evidence that strong conspecific mate preferences in each species form significant sexual isolation. We find that these mating preferences are learned in one species but may be genetic in the other:\ P. gossypinus\ sexually imprints on its parents, but innate biases or social learning affects mating preferences in\ P. leucopus. Our study demonstrates that sexually imprinting contributes to reproductive isolation that reduces hybridization between otherwise inter-fertile species, supporting a previously underappreciated role for learning in mammalian speciation.}, author = {Delaney, E.K. and Hoekstra, H. E.} } @article {932666, title = {The ultimate and proximate mechanisms driving the evolution of long tails in forest deer mice}, journal = {Evolution}, volume = {71}, year = {2017}, month = {2017}, pages = {261-273}, abstract = {

Understanding both the role of selection in driving phenotypic change and its underlying genetic basis remain major challenges in evolutionary biology. Here, we use modern tools to revisit a classic system of local adaptation in the North American deer mouse, Peromyscus maniculatus, which occupies two main habitat types: prairie and forest. Using historical collections, we find that forest-dwelling mice have longer tails than those from nonforested habitat, even when we account for individual and population relatedness. Using genome-wide SNP data, we show that mice from forested habitats in the eastern and western parts of their range form separate clades, suggesting that increased tail length evolved independently. We find that forest mice in the east and west have both more and longer caudal vertebrae, but not trunk vertebrae, than nearby prairie forms. By intercrossing prairie and forest mice, we show that the number and length of caudal vertebrae are not correlated in this recombinant population, indicating that variation in these traits is controlled by separate genetic loci. Together, these results demonstrate convergent evolution of the long-tailed forest phenotype through two distinct genetic mechanisms, affecting number and length of vertebrae, and suggest that these morphological changes {\textemdash} either independently or together {\textemdash} are adaptive.

}, author = {Kingsley, E. P. and Kozak, K. M. and Pfeifer, SP and Yang, D-S and Hoekstra, HE} } @article {1018731, title = {Evolution and genetics of precocious burrowing behavior in Peromyscus mice.}, journal = {Current Biology}, volume = {27}, year = {2017}, pages = {3837-3845}, abstract = {A central challenge in biology is to understand how innate behaviors evolve between closely related species. One way to elucidate how differences arise is to compare the development of behavior in species with distinct adult traits. Here, we report that\ Peromyscus polionotus\ is strikingly precocious with regard to burrowing behavior, but not other behaviors, compared to its sister species\ P. maniculatus. In\ P. polionotus, burrows were excavated as early as 17 days of age, while\ P. maniculatus\ did not build burrows until 10 days later. Moreover, the well-known differences in burrow architecture between adults of these species --\ P. polionotus\ adults excavate long burrows with an escape tunnel, while\ P. maniculatus\ dig short, single-tunnel burrows -- were intact in juvenile burrowers. To test whether this juvenile behavior is influenced by early-life environment, pups of both species were reciprocally cross-fostered. Fostering did not alter the characteristic burrowing behavior of either species, suggesting these differences are genetic. In backcross F2 hybrids, we show that precocious burrowing and adult tunnel length are genetically correlated, and that a single\ P. polionotus\ allele in a genomic region linked to adult tunnel length is predictive of precocious burrow construction. The co-inheritance of developmental and adult traits indicates the same genetic region -- either a single gene with pleiotropic effects, or closely linked genes -- acts on distinct aspects of the same behavior across life stages. Such genetic variants likely affect behavioral drive (i.e. motivation) to burrow, and thereby affect both the development and adult expression of burrowing behavior.}, author = {Metz, H. C. and Bedford, NL and Pan, L and Hoekstra, HE} } @article {995566, title = {The genetic basis of parental care evolution in monogamous mice}, journal = {Nature}, volume = {554}, year = {2017}, pages = {434-439}, abstract = {

Parental care is essential for the survival of mammals, yet the mechanisms underlying its evolution remain largely unknown. Here we show that two sister species of mice, Peromyscus polionotus and Peromyscus maniculatus, have large and heritable differences in parental behaviour. Using quantitative genetics, we identify 12 genomic regions that affect parental care, 8 of which have sex-specific effects, suggesting that parental care can evolve independently in males and females. Furthermore, some regions affect parental care broadly, whereas others affect specific behaviours, such as nest building. Of the genes linked to differences in nest-building behaviour, vasopressin is differentially expressed in the hypothalamus of the two species, with increased levels associated with less nest building. Using pharmacology in Peromyscus and chemogenetics in Mus, we show that vasopressin inhibits nest building but not other parental behaviours. Together, our results indicate that variation in an ancient neuropeptide contributes to interspecific differences in parental care.\ 

}, author = {Andres Bendesky and Young-Mi Kwon and Jean-Marc Lassance and Caitlin L. Lewarch and Shenqin Yao and Brant K. Peterson and Meng Xiao He and Catherine Dulac and Hopi E. Hoekstra} } @article {872621, title = {Peromyscus burrowing: A model system for behavioral evolution}, journal = {Seminars in Cell and Developmental Biology}, volume = {61}, year = {2017}, pages = {107-114}, abstract = {

A major challenge to understanding the genetic basis of complex behavioral evolution is the quantification of complex behaviors themselves. Deer mice of the genus\ Peromyscusvary in their burrowing behavior, which leaves behind a physical trace that is easily preserved and measured. Moreover, natural burrowing behaviors are recapitulated in the lab, and there is a strong heritable component. Here we discuss potential mechanisms driving variation in burrows with an emphasis on two sister species:\ P. maniculatus, which digs a simple, short burrow, and\ P. polionotus, which digs a long burrow with a complex architecture. A forward-genetic cross between these two species identified several genomic regions associated with burrow traits, suggesting this complex behavior has evolved in a modular fashion. Because burrow differences are most likely due to differences in behavior circuits,\ Peromyscus\ burrowing offers an exciting opportunity to link genetic variation between natural populations to evolutionary changes in neural circuits.

}, author = {Hu, C.K. and Hoekstra, H. E.} } @article {841566, title = {The role of isoforms in the evolution of cryptic coloration in Peromyscus mice}, journal = {Molecular Ecology}, volume = {26}, year = {2017}, pages = {245-258}, abstract = {

A central goal of evolutionary biology is to understand the molecular mechanisms underlying phenotypic adaptation. While the contribution of protein-coding and\ cis-regulatory mutations to adaptive traits have been well documented, additional sources of variation{\textemdash}such as the production of alternative RNA transcripts from a single gene, or isoforms{\textemdash}have been understudied. Here, we focus on the pigmentation gene\ Agouti, known to express multiple alternative transcripts, to investigate the role of isoform usage in the evolution of cryptic color phenotypes in deer mice (genus\ Peromyscus). We first characterize the\ Agouti\ isoforms expressed in the\ Peromyscus\ skin and find two novel isoforms not previously identified in\ Mus. Next, we show that a locally adapted light-colored population of\ P. maniculatus\ living on the Nebraska Sand Hills shows an up-regulation of a single\ Agouti\ isoform, termed 1C, compared to their ancestral dark-colored conspecifics. Using\ in vitro\ assays, we show that this preference for isoform 1C may be driven by isoform-specific differences in translation. In addition, using an admixed population of wild-caught mice, we find that variation in overall\ Agouti\ expression maps to a region near exon 1C, which also has patterns of nucleotide variation consistent with strong positive selection. Finally, we show that the independent evolution of cryptic light pigmentation in a different species,\ P. polionotus, has been driven by a preference for the same\ Agouti\ isoform. Together, these findings present an example of the role of alternative transcript processing in adaptation and demonstrate molecular convergence at the level of isoform regulation.

}, author = {Mallarino, R. and Linden, T. A. and Linnen, C. R. and Hoekstra, H. E.} } @article {910856, title = {Developmental genetics in emerging rodent models: Case studies and perspectives}, journal = {Current Opinion in Genetics \& Development}, volume = {39}, year = {2016}, pages = {182-186}, abstract = {

For decades, mammalian developmental genetic studies have focused almost entirely on two laboratory models: Mus and Rattus, species that breed readily in the laboratory and for which a wealth of molecular and genetic resources exist. These species alone, however, do not capture the remarkable diversity of morphological, behavioural and physiological traits seen across rodents, a group that represents \>40\% of all mammal species. Due to new advances in molecular tools and genomic technologies, studying the developmental events underlying natural variation in a wide range of species for a wide range of traits has become increasingly feasible. Here we review several recent studies and discuss how they not only provided technical resources for newly emerging rodent models in developmental genetics but also are instrumental in further encouraging scientists, from a wide range of research fields, to capitalize on the great diversity in development that has evolved among rodents.\ 

}, author = {Mallarino, R. and Hoekstra, H. E. and Manceau, M.} } @article {910871, title = {Developmental mechanisms of stripe patterns in rodents}, journal = {Nature}, volume = {539}, year = {2016}, month = {02 Nov, 2016}, pages = {518-523}, abstract = {

Mammalian colour patterns are among the most recognizable characteristics found in nature and can have a profound impact on fitness. However, little is known about the mechanisms underlying the formation and subsequent evolution of these patterns. Here we show that, in the African striped mouse (Rhabdomys pumilio), periodic dorsal stripes result from underlying differences in melanocyte maturation, which give rise to spatial variation in hair colour. We identify the transcription factor ALX3 as a regulator of this process. In embryonic dorsal skin, patterned expression of Alx3 precedes pigment stripes and acts to directly repress Mitf, a master regulator of melanocyte differentiation, thereby giving rise to light-coloured hair. Moreover, Alx3 is upregulated in the light stripes of chipmunks, which have independently evolved a similar dorsal pattern. Our results show a previously undescribed mechanism for modulating spatial variation in hair colour and provide insights into how phenotypic novelty evolves.

}, author = {Mallarino, R. and Henegar, C. and Mirasierra, M. and Manceau, M.C. and Shradin, C. and Vallejo, M. and Beronja, S. and Barsh, G. S. and Hoekstra, H. E.} } @article {910851, title = {Ecological genetics: A key gene for mimicry and melanism}, journal = {Current Biology }, volume = {26}, year = {2016}, month = {2016}, pages = {R802-804}, abstract = {

\ Mimicry and melanism in Lepidoptera provided the first convincing examples of natural selection in action. Genetic analysis has now shown that, surprisingly, mimicry in Heliconius\ butterflies and melanism in peppered moths are switched at precisely the same gene: cortex .

}, author = {Mallet, J. and Hoekstra, H. E.} } @article {910861, title = {The evolving neural and genetic architecture of vertebrate olfaction}, journal = {Current Biology}, volume = {26}, year = {2016}, month = {24 Oct, 2016}, pages = {R1039-R1049}, abstract = {

Evolution sculpts the olfactory nervous system in response to the unique sensory challenges facing each species. In vertebrates, dramatic and diverse adaptations to the chemical environment are possible because of the hierarchical structure of the olfactory receptor (OR) gene superfamily: expansion or contraction of OR subfamilies accompanies major changes in habitat and lifestyle; independent selection on OR subfamilies can permit local adaptation or conserved chemical communication; and genetic variation in single OR genes can alter odor percepts and behaviors driven by precise chemical cues. However, this genetic flexibility con- trasts with the relatively fixed neural architecture of the vertebrate olfactory system, which requires that new olfactory receptors integrate into segregated and functionally distinct neural pathways. This organization allows evolution to couple critical chemical signals with selectively advantageous responses, but also con- strains relationships between olfactory receptors and behavior. The coevolution of the OR repertoire and the olfactory system therefore reveals general principles of how the brain solves specific sensory problems and how it adapts to new ones.

}, author = {Bear, D.M. and Lassance, J.M. and Hoekstra, H. E. and Datta, S.R.} } @article {910866, title = {The genetic basis and fitness consequences of sperm midpiece size in deer mice}, journal = {Nature Communications}, volume = {7}, year = {2016}, month = {2 Dec 2016}, pages = {13652}, abstract = {

An extensive array of reproductive traits varies among species, yet the genetic mechanisms that enable divergence, often over short evolutionary timescales, remain elusive. Here we examine two sister-species of Peromyscus mice with divergent mating systems. We find that the promiscuous species produces sperm with longer midpiece than the monogamous species, and midpiece size correlates positively with competitive ability and swimming performance. Using forward genetics, we identify a gene associated with midpiece length: Prkar1a, which encodes the R1a regulatory subunit of PKA. R1a localizes to midpiece in Peromyscus and is differentially expressed in mature sperm of the two species yet is similarly abundant in the testis. We also show that genetic variation at this locus accurately predicts male reproductive success. Our findings suggest that rapid evolution of reproductive traits can occur through cell type-specific changes to ubiquitously expressed genes and have an important effect on fitness.

}, author = {Fisher, H. S. and E. Jacobs-Palmer and Lassance, J.M. and Hoekstra, H. E.} } @article {844701, title = {A collection of non-human primate computed tomography scans housed in MorphoSource, a repository for 3D data}, journal = {Scientific Data}, volume = {3}, year = {2016}, abstract = {

A dataset of high-resolution microCT scans of primate skulls (crania and mandibles) and certain postcranial elements was collected to address questions about primate skull morphology. The sample consists of 489 scans taken from 431 specimens, representing 59 species of most Primate families. These data have transformative reuse potential as such datasets are necessary for conducting high power research into primate evolution, but require significant time and funding to collect. Similar datasets were previously only available to select research groups across the world. The physical specimens are vouchered at Harvard{\textquoteright}s Museum of Comparative Zoology. The data collection took place at the Center for Nanoscale Systems at Harvard. The dataset is archived on MorphoSource.org. Though this is the largest high fidelity comparative dataset yet available, its provisioning on a web archive that allows unlimited researcher contributions promises a future with vastly increased digital collections available at researchers{\textquoteright} finger tips.

}, author = {Copes, L.E. and Lucas, L.M. and Thostenson, J.O. and Hoekstra, H. E. and Boyer, D.M.} } @article {841576, title = {A family of non-GPCR chemosensors defines an alternative logic for mammalian olfaction}, journal = {Cell}, volume = {165}, year = {2016}, month = {2016}, pages = {1734-1748}, abstract = {

Odor perception in mammals is mediated by parallel sensory pathways that convey distinct information about the olfactory world. Multiple olfactory subsystems express characteristic seven-transmembrane G-protein-coupled receptors (GPCRs) in a one-receptor-per-neuron pattern that facilitates odor discrimination. Sensory neurons of the {\textquotedblleft}necklace{\textquotedblright} subsystem are nestled within the recesses of the olfactory epithelium and detect diverse odorants; however, they do not express known GPCR odor receptors. Here, we report that members of the four-pass transmembrane MS4A protein family are chemosensors expressed within necklace sensory neurons. These receptors localize to sensory endings and confer responses to ethologically relevant ligands, including pheromones and fatty acids, in\ vitro and in\ vivo. Individual necklace neurons co-express many MS4A proteins and are activated by multiple MS4A ligands; this pooling of information suggests that the necklace is organized more like subsystems for taste than for smell. The MS4As therefore define a distinct mechanism and functional logic for mammalian olfaction.


}, author = {Greer, P.L. and Bear, D.M. and Lassance, J.M. and Bloom, M.L. and Tsukahara,T. and Masada, F.K. and Nolan, A.C. and Hoekstra, H. E. and Datta, S.R.} } @article {741621, title = {Peromyscus mice as a model for studying natural variation}, journal = {eLIFE}, volume = {4:eO6813}, year = {2015}, abstract = {

The deer mouse (genus Peromyscus) is the most abundant mammal in North America, and it occupies almost every type of terrestrial habitat. It is not surprising therefore that the natural history of Peromyscus is among the best studied of any small mammal. For decades, the deer mouse has contributed to our understanding of population genetics, disease ecology, longevity, endocrinology and behavior. Over a century{\textquoteright}s worth of detailed descriptive studies of Peromyscus in the wild,
coupled with emerging genetic and genomic techniques, have now positioned these mice as model organisms for the study of natural variation and adaptation. Recent work, combining field observations and laboratory experiments, has lead to exciting advances in a number of fields{\textemdash}from evolution and genetics, to physiology and neurobiology.

}, author = {Bedford, NL and Hoekstra, HE} } @article {597886, title = {Direct gamete sequencing reveals no evidence for segregation distorters in house mouse hybrids}, journal = {PLoS One}, volume = {10}, year = {2015}, pages = {e0131933}, abstract = {

Understanding the molecular basis of species formation is an important goal in evolutionary genetics, and Dobzhansky-Muller incompatibilities are thought to be a common source of postzygotic reproductive isolation between closely related lineages. However, the evolutionary forces that lead to the accumulation of such incompatibilities between diverging taxa are poorly understood. Segregation distorters are believed to be an important source of Dobzhansky-Muller incompatibilities between Drosophila species and crop plants, but it remains unclear if these selfish genetic elements contribute to reproductive isolation in other species. Here, we collected viable sperm from first-generation hybrid male progeny of Mus musculus castaneus and M. m. domesticus, two subspecies of rodent in the earliest stages of speciation. We then genotyped millions of single nucleotide polymorphisms in these gamete pools and tested for a skew in the frequency of parental alleles across the genome. We show that segregation distorters are not measurable contributors to observed infertility in these hybrid males, despite sufficient statistical power to detect even weak segregation distortion with our novel method. Thus, reduced hybrid male fertility in crosses between these nascent species is attributable to other evolutionary forces.

}, author = {Corbett-Detig, R. and E. Jacobs-Palmer and Hartl, D. L. and Hoekstra, HE} } @article {597891, title = {Does evolutionary biology need a rethink? Counterpoint: No, all is well}, journal = {Nature }, volume = {514}, year = {2014}, pages = {161-4}, abstract = {

Theory accommodates evidence through relentless synthesis, say Gregory A. Wray, Hopi E. Hoekstra and colleagues.

}, author = {Wray, G. A. and D.A. Futuyma and Lenski, R. E. and T.F.C. MacKay and Schluter, D. and J.E. Strassman and Hoekstra, HE} } @article {549226, title = {The dynamics of sperm cooperation in a competitive environment}, journal = {Proceedings of the Royal Society B}, volume = {281}, number = {1790}, year = {2014}, note = {

Fisher, Heidi SGiomi, LucaHoekstra, Hopi EMahadevan, LengK99 HD071972/HD/NICHD NIH HHS/Howard Hughes Medical Institute/Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov{\textquoteright}tEngland2014/07/25 06:00Proc Biol Sci. 2014 Sep 7;281(1790). pii: 20140296. doi: 10.1098/rspb.2014.0296.

}, month = {Sep 7}, pages = {20140296}, abstract = {

Sperm cooperation has evolved in a variety of taxa and is often considered a response to sperm competition, yet the benefit of this form of collective movement remains unclear. Here, we use fine-scale imaging and a minimal mathematical model to study sperm aggregation in the rodent genus Peromyscus. We demonstrate that as the number of sperm cells in an aggregate increase, the group moves with more persistent linearity but without increasing speed. This benefit, however, is offset in larger aggregates as the geometry of the group forces sperm to swim against one another. The result is a non-monotonic relationship between aggregate size and average velocity with both a theoretically predicted and empirically observed optimum of six to seven sperm per aggregate. To understand the role of sexual selection in driving these sperm group dynamics, we compared two sister-species with divergent mating systems. We find that sperm of Peromyscus maniculatus (highly promiscuous), which have evolved under intense competition, form optimal-sized aggregates more often than sperm of Peromyscus polionotus (strictly monogamous), which lack competition. Our combined mathematical and experimental study of coordinated sperm movement reveals the importance of geometry, motion and group size on sperm velocity and suggests how these physical variables interact with evolutionary selective pressures to regulate cooperation in competitive environments.

}, isbn = {1471-2954 (Electronic)0962-8452 (Linking)}, author = {Fisher, H. S. and Giomi, L. and Hoekstra, H. E. and L. Mahadevan} } @article {549406, title = {On the prospect of identifying adaptive loci in recently bottlenecked populations}, journal = {PLoS One}, volume = {9}, number = {11}, year = {2014}, note = {

Poh, Yu-PingDomingues, Vera SHoekstra, Hopi EJensen, Jeffrey DengHoward Hughes Medical Institute/Research Support, Non-U.S. Gov{\textquoteright}t2014/11/11 06:00PLoS One. 2014 Nov 10;9(11):e110579. doi: 10.1371/journal.pone.0110579. eCollection 2014.

}, pages = {e110579}, abstract = {

Identifying adaptively important loci in recently bottlenecked populations - be it natural selection acting on a population following the colonization of novel habitats in the wild, or artificial selection during the domestication of a breed - remains a major challenge. Here we report the results of a simulation study examining the performance of available population-genetic tools for identifying genomic regions under selection. To illustrate our findings, we examined the interplay between selection and demography in two species of Peromyscus mice, for which we have independent evidence of selection acting on phenotype as well as functional evidence identifying the underlying genotype. With this unusual information, we tested whether population-genetic-based approaches could have been utilized to identify the adaptive locus. Contrary to published claims, we conclude that the use of the background site frequency spectrum as a null model is largely ineffective in bottlenecked populations. Results are quantified both for site frequency spectrum and linkage disequilibrium-based predictions, and are found to hold true across a large parameter space that encompasses many species and populations currently under study. These results suggest that the genomic footprint left by selection on both new and standing variation in strongly bottlenecked populations will be difficult, if not impossible, to find using current approaches.

}, isbn = {1932-6203 (Electronic)1932-6203 (Linking)}, author = {Poh, Y. P. and Domingues, V. S. and Hoekstra, HE and Jensen, J. D.} } @article {549356, title = {Adaptive evolution of multiple traits through multiple mutations at a single gene}, journal = {Science}, volume = {339}, number = {6125}, year = {2013}, note = {

Linnen, Catherine RPoh, Yu-PingPeterson, Brant KBarrett, Rowan D HLarson, Joanna GJensen, Jeffrey DHoekstra, Hopi Eeng308796/European Research Council/InternationalResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov{\textquoteright}tResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.New York, N.Y.2013/03/16 06:00Science. 2013 Mar 15;339(6125):1312-6. doi: 10.1126/science.1233213.

Paper selected by Faculty of 1000

}, month = {Mar 15}, pages = {1312-6}, abstract = {

The identification of precise mutations is required for a complete understanding of the underlying molecular and evolutionary mechanisms driving adaptive phenotypic change. Using plasticine models in the field, we show that the light coat color of deer mice that recently colonized the light-colored soil of the Nebraska Sand Hills provides a strong selective advantage against visually hunting predators. Color variation in an admixed population suggests that this light Sand Hills phenotype is composed of multiple traits. We identified distinct regions within the Agouti locus associated with each color trait and found that only haplotypes associated with light trait values have evidence of selection. Thus, local adaptation is the result of independent selection on many mutations within a single locus, each with a specific effect on an adaptive phenotype, thereby minimizing pleiotropic consequences.

}, keywords = {*Biological Evolution, *Multifactorial Inheritance, Adaptation, Physiological/*genetics, Agouti Signaling Protein/genetics, Animals, Color, Food Chain, Mutation, Organic Chemicals, Peromyscus/genetics/*physiology, Pigmentation/*genetics, Selection, Genetic}, isbn = {1095-9203 (Electronic)0036-8075 (Linking)}, author = {Linnen, C. R. and Poh, Y. P. and Peterson, B. K. and Barrett, R. D. and Larson, J. G. and Jensen, J. D. and Hoekstra, HE} } @article {549471, title = {Discrete genetic modules are responsible for complex burrow evolution in Peromyscus mice}, journal = {Nature }, volume = {493}, number = {7432}, year = {2013}, note = {

Weber, Jesse NPeterson, Brant KHoekstra, Hopi EengResearch Support, Non-U.S. Gov{\textquoteright}tResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.England2013/01/18 06:00Nature. 2013 Jan 17;493(7432):402-5. doi: 10.1038/nature11816.

Commentaries in Science\ and Nature\ News in Focus,\ Editorial\ Natural History and\ News and Views; auditory commentary on\ Nature Podcast.

Paper selected by Faculty of 1000

}, month = {Jan 17}, pages = {402-5}, abstract = {

Relative to morphological traits, we know little about how genetics influence the evolution of complex behavioural differences in nature. It is unclear how the environment influences natural variation in heritable behaviour, and whether complex behavioural differences evolve through few genetic changes, each affecting many aspects of behaviour, or through the accumulation of several genetic changes that, when combined, give rise to behavioural complexity. Here we show that in nature, oldfield mice (Peromyscus polionotus) build complex burrows with long entrance and escape tunnels, and that burrow length is consistent across populations, although burrow depth varies with soil composition. This burrow architecture is in contrast with the small, simple burrows of its sister species, deer mice (P. maniculatus). When investigated under laboratory conditions, both species recapitulate their natural burrowing behaviour. Genetic crosses between the two species reveal that the derived burrows of oldfield mice are dominant and evolved through the addition of multiple genetic changes. In burrows built by first-generation backcross mice, entrance-tunnel length and the presence of an escape tunnel can be uncoupled, suggesting that these traits are modular. Quantitative trait locus analysis also indicates that tunnel length segregates as a complex trait, affected by at least three independent genetic regions, whereas the presence of an escape tunnel is associated with only a single locus. Together, these results suggest that complex behaviours--in this case, a classic {\textquoteright}extended phenotype{\textquoteright}--can evolve through multiple genetic changes each affecting distinct behaviour modules.

}, keywords = {*Biological Evolution, *Ecosystem, Animals, Animals, Wild/genetics/physiology, Behavior, Animal/*physiology, Crosses, Genetic, Evolution, Molecular, Female, Genotype, Male, Models, Genetic, Nesting Behavior/physiology, Peromyscus/*genetics/*physiology, Quantitative Trait Loci/*genetics}, isbn = {1476-4687 (Electronic)0028-0836 (Linking)}, author = {Weber, J. N. and Peterson, B. K. and Hoekstra, HE} } @article {549321, title = {The draft genome of a socially polymorphic halictid bee, Lasioglossum albipes}, journal = {Genome Biology}, volume = {14}, number = {12}, year = {2013}, note = {

Kocher, Sarah DLi, CaiYang, WeiTan, HaoYi, Soojin VYang, XingyuHoekstra, Hopi EZhang, GuojiePierce, Naomi EYu, Douglas WengResearch Support, Non-U.S. Gov{\textquoteright}tEngland2013/12/24 06:00Genome Biol. 2013 Dec 20;14(12):R142. doi: 10.1186/gb-2013-14-12-r142.

}, pages = {R142}, abstract = {

BACKGROUND: Taxa that harbor natural phenotypic variation are ideal for ecological genomic approaches aimed at understanding how the interplay between genetic and environmental factors can lead to the evolution of complex traits. Lasioglossum albipes is a polymorphic halictid bee that expresses variation in social behavior among populations, and common-garden experiments have suggested that this variation is likely to have a genetic component. RESULTS: We present the L. albipes genome assembly to characterize the genetic and ecological factors associated with the evolution of social behavior. The de novo assembly is comparable to other published social insect genomes, with an N50 scaffold length of 602 kb. Gene families unique to L. albipes are associated with integrin-mediated signaling and DNA-binding domains, and several appear to be expanded in this species, including the glutathione-s-transferases and the inositol monophosphatases. L. albipes has an intact DNA methylation system, and in silico analyses suggest that methylation occurs primarily in exons. Comparisons to other insect genomes indicate that genes associated with metabolism and nucleotide binding undergo accelerated evolution in the halictid lineage. Whole-genome resequencing data from one solitary and one social L. albipes female identify six genes that appear to be rapidly diverging between social forms, including a putative odorant receptor and a cuticular protein. CONCLUSIONS: L. albipes represents a novel genetic model system for understanding the evolution of social behavior. It represents the first published genome sequence of a primitively social insect, thereby facilitating comparative genomic studies across the Hymenoptera as a whole.

}, isbn = {1465-6914 (Electronic)1465-6906 (Linking)}, author = {Kocher, S. D. and Li, C. and W. Yang and Tan, H. and Yi, S. V. and Yang, X. and Hoekstra, HE and Zhang, G. and Pierce, N. E. and Yu, D. W.} } @article {549361, title = {Evolutionary biology for the 21st century}, journal = {PLoS Biology}, volume = {11:e1001466}, number = {1}, year = {2013}, note = {

Losos, Jonathan BArnold, Stevan JBejerano, GillBrodie, E D 3rdHibbett, DavidHoekstra, Hopi EMindell, David PMonteiro, AntoniaMoritz, CraigOrr, H AllenPetrov, Dmitri ARenner, Susanne SRicklefs, Robert ESoltis, Pamela STurner, Thomas LengResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.2013/01/16 06:00PLoS Biol. 2013;11(1):e1001466. doi: 10.1371/journal.pbio.1001466. Epub 2013 Jan 8.

Paper selected by Faculty of 1000

}, keywords = {*Biological Evolution, *Genetic Variation, Biodiversity, Evolution, Molecular, Humans, Phylogeny}, isbn = {1545-7885 (Electronic)1544-9173 (Linking)}, author = {Losos, J. B. and Arnold, S. J. and Bejerano, G. and Brodie, ED and Hibbett, D. and Hoekstra, HE and Mindell, D. P. and Monteiro, A. and Moritz, C. and Orr, H. A. and Petrov, D. A. and Renner, S. S. and Ricklefs, R. E. and Soltis, P. S. and Turner, T. L.} } @article {549326, title = {Loss of schooling behavior in cavefish through sight-dependent and sight-independent mechanisms}, journal = {Current Biology}, volume = {23}, number = {19}, year = {2013}, note = {

Kowalko, Johanna ERohner, NicolasRompani, Santiago BPeterson, Brant KLinden, Tess AYoshizawa, MasatoKay, Emily HWeber, JesseHoekstra, Hopi EJeffery, William RBorowsky, RichardTabin, Clifford JengR01 EY014619/EY/NEI NIH HHS/R01 HD047360/HD/NICHD NIH HHS/Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov{\textquoteright}tResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.England2013/09/17 06:00Curr Biol. 2013 Oct 7;23(19):1874-83. doi: 10.1016/j.cub.2013.07.056. Epub 2013 Sep 12.

}, month = {Oct 7}, pages = {1874-83}, abstract = {

BACKGROUND: Surface populations of Astyanax mexicanus, living in rivers like their common ancestors, school, while several, independently derived cave populations of the same species have lost schooling behavior. RESULTS: We quantify schooling behavior in individual A. mexicanus and identify quantitative trait loci (QTL) for this trait. We find that the evolutionary modulation of schooling has both vision-dependent and -independent components. We also quantify differences in the lateral line and vision between cavefish and surface fish and relate these differences to the evolutionary loss of schooling behavior. We provide evidence that a monoamine neurotransmitter may have played a role in the evolution of schooling behavior. CONCLUSIONS: We find that vision is essential for schooling tendency in A. mexicanus, while the lateral line has a small effect on this behavior. Schooling behavior in A. mexicanus has evolved both through changes in sensory systems and through changes in genetic loci that likely act downstream of sensory inputs.

}, keywords = {Adaptation, Physiological/genetics/*physiology, Animals, Behavior, Animal/drug effects/*physiology, Biological Evolution, Brain/metabolism, Caves, Characidae/genetics/*physiology, Dopamine/metabolism, Fluoxetine/pharmacology, Lateral Line System/*physiology, Lens, Crystalline/physiology, Monoamine Oxidase Inhibitors/pharmacology, Neurotransmitter Agents/antagonists \& inhibitors, Quantitative Trait Loci/genetics, Selection, Genetic, Selegiline/pharmacology, Serotonin Uptake Inhibitors/pharmacology, Serotonin/metabolism, Vision, Ocular/*physiology}, isbn = {1879-0445 (Electronic)0960-9822 (Linking)}, author = {Kowalko, J. E. and Rohner, N. and Rompani, S. B. and Peterson, B. K. and Linden, T. A. and Yoshizawa, M. and Kay, E. H. and Weber, J. and Hoekstra, HE and Jeffery, W. R. and Borowsky, R. and Tabin, C. J.} } @article {597961, title = {Mus spicilegus}, journal = {Current Biology }, volume = {20}, year = {2012}, pages = {858-859}, abstract = {

What or who is Mus spicilegus? Mus spicilegus, aka {\textquoteleft}the mound-building mouse{\textquoteright}, is a rather nondescript, brown mouse that looks just like its close relative, the commensal house mouse (Mus musculus). In fact, they look so much like house mice that the first individuals described in 1840 from a garden in Odessa probably were house mice. Its epithet {\textquoteleft}spicilegus{\textquoteright} is derived from the Latin, spica meaning a spike of grain, and legere, to collect, which makes sense, since these mice do in fact gather grains.

}, author = {Tong, W. and Hoekstra, HE} } @article {549401, title = {Double digest RADseq: An inexpensive method for de novo SNP discovery and genotyping in model and non-model species}, journal = {PLoS One}, volume = {7}, number = {5}, year = {2012}, note = {

Peterson, Brant KWeber, Jesse NKay, Emily HFisher, Heidi SHoekstra, Hopi EengResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov{\textquoteright}tResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.2012/06/08 06:00PLoS One.\ 2012;7(5):e37135. doi: 10.1371/journal.pone.0037135. Epub 2012 May 31

ddRAD PROTOCOL

Codes

Paper selected by Faculty of 1000

}, pages = {e37135}, abstract = {

The ability to efficiently and accurately determine genotypes is a keystone technology in modern genetics, crucial to studies ranging from clinical diagnostics, to genotype-phenotype association, to reconstruction of ancestry and the detection of selection. To date, high capacity, low cost genotyping has been largely achieved via "SNP chip" microarray-based platforms which require substantial prior knowledge of both genome sequence and variability, and once designed are suitable only for those targeted variable nucleotide sites. This method introduces substantial ascertainment bias and inherently precludes detection of rare or population-specific variants, a major source of information for both population history and genotype-phenotype association. Recent developments in reduced-representation genome sequencing experiments on massively parallel sequencers (commonly referred to as RAD-tag or RADseq) have brought direct sequencing to the problem of population genotyping, but increased cost and procedural and analytical complexity have limited their widespread adoption. Here, we describe a complete laboratory protocol, including a custom combinatorial indexing method, and accompanying software tools to facilitate genotyping across large numbers (hundreds or more) of individuals for a range of markers (hundreds to hundreds of thousands). Our method requires no prior genomic knowledge and achieves per-site and per-individual costs below that of current SNP chip technology, while requiring similar hands-on time investment, comparable amounts of input DNA, and downstream analysis times on the order of hours. Finally, we provide empirical results from the application of this method to both genotyping in a laboratory cross and in wild populations. Because of its flexibility, this modified RADseq approach promises to be applicable to a diversity of biological questions in a wide range of organisms.

}, keywords = {*Genotype, *Polymorphism, Single Nucleotide, Animals, Animals, Outbred Strains, DNA Restriction Enzymes/*metabolism, genome, Reproducibility of Results, Rodentia, Sequence Analysis, DNA/*methods}, isbn = {1932-6203 (Electronic)1932-6203 (Linking)}, author = {Peterson, B. K. and Weber, J. N. and Kay, E. H. and Fisher, H. S. and Hoekstra, HE} } @article {549221, title = {Evidence of adaptation from ancestral variation in young populations of beach mice}, journal = {Evolution}, volume = {66}, number = {10}, year = {2012}, note = {

Domingues, Vera SPoh, Yu-PingPeterson, Brant KPennings, Pleuni SJensen, Jeffrey DHoekstra, Hopi EengComparative StudyResearch Support, Non-U.S. Gov{\textquoteright}tResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.2012/10/03 06:00Evolution. 2012 Oct;66(10):3209-23. doi: 10.1111/j.1558-5646.2012.01669.x. Epub 2012 May 4.

}, month = {Oct}, pages = {3209-23}, abstract = {

To understand how organisms adapt to novel habitats, which involves both demographic and selective events, we require knowledge of the evolutionary history of populations and also selected alleles. There are still few cases in which the precise mutations (and hence, defined alleles) that contribute to adaptive change have been identified in nature; one exception is the genetic basis of camouflaging pigmentation of oldfield mice (Peromyscus polionotus) that have colonized the sandy dunes of Florida{\textquoteright}s Gulf Coast. To quantify the genomic impact of colonization as well as the signature of selection, we resequenced 5000 1.5-kb noncoding loci as well as a 160-kb genomic region surrounding the melanocortin-1 receptor (Mc1r), a gene that contributes to pigmentation differences, in beach and mainland populations. Using a genome-wide phylogenetic approach, we recovered a single monophyletic group comprised of beach mice, consistent with a single colonization event of the Gulf Coast. We also found evidence of a severe founder event, estimated to have occurred less than 3000 years ago. In this demographic context, we show that all beach subspecies share a single derived light Mc1r allele, which was likely selected from standing genetic variation that originated in the mainland. Surprisingly, we were unable to identify a clear signature of selection in the Mc1r region, despite independent evidence that this locus contributes to adaptive coloration. Nonetheless, these data allow us to reconstruct and compare the evolutionary history of populations and alleles to better understand how adaptive evolution, following the colonization of a novel habitat, proceeds in nature.

}, keywords = {*Adaptation, Biological, *Founder Effect, *Selection, Genetic, Alleles, Animals, Biological Evolution, Genetic Variation, genome, Peromyscus/*genetics, Pigmentation/genetics, Receptor, Melanocortin, Type 1/*genetics, Southeastern United States}, isbn = {1558-5646 (Electronic)0014-3820 (Linking)}, author = {Domingues, V. S. and Poh, Y. P. and Peterson, B. K. and Pennings, P. S. and Jensen, J. D. and Hoekstra, H. E.} } @article {549246, title = {Genomics: Stickleback is the catch of the day}, journal = {Nature }, volume = {484}, number = {7392}, year = {2012}, note = {

Hoekstra, Hopi EengCommentNewsEngland2012/04/07 06:00Nature. 2012 Apr 4;484(7392):46-7. doi: 10.1038/484046a.

}, month = {Apr 5}, pages = {46-7}, keywords = {*Biological Evolution, Adaptation, Physiological/*genetics, Animals, Female, Genome/*genetics, Smegmamorpha/*genetics}, isbn = {1476-4687 (Electronic)0028-0836 (Linking)}, author = {Hoekstra, HE} } @article {549331, title = {Unraveling the thread of nature{\textquoteright}s tapestry: The genetics of diversity and convergence in animal pigmentation}, journal = {Pigment Cell \& Melanoma Research}, volume = {25}, number = {4}, year = {2012}, note = {

Kronforst, Marcus RBarsh, Gregory SKopp, ArtyomMallet, JamesMonteiro, AntoniaMullen, Sean PProtas, MeredithRosenblum, Erica BSchneider, Christopher JHoekstra, Hopi EengResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov{\textquoteright}tResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.ReviewEngland2012/05/15 06:00Pigment Cell Melanoma Res. 2012 Jul;25(4):411-33. doi: 10.1111/j.1755-148X.2012.01014.x.

}, month = {Jul}, pages = {411-33}, abstract = {

Animals display incredibly diverse color patterns yet little is known about the underlying genetic basis of these phenotypes. However, emerging results are reshaping our view of how the process of phenotypic evolution occurs. Here, we outline recent research from three particularly active areas of investigation: melanin pigmentation in Drosophila, wing patterning in butterflies, and pigment variation in lizards. For each system, we highlight (i) the function and evolution of color variation, (ii) various approaches that have been used to explore the genetic basis of pigment variation, and (iii) conclusions regarding the genetic basis of convergent evolution which have emerged from comparative analyses. Results from these studies indicate that natural variation in pigmentation is a particularly powerful tool to examine the molecular basis of evolution, especially with regard to convergent or parallel evolution. Comparison of these systems also reveals that the molecular basis of convergent evolution is heterogeneous, sometimes involving conserved mechanisms and sometimes not. In the near future, additional work in other emerging systems will substantially expand the scope of available comparisons.

}, keywords = {*Genetic Variation, *Nature, Animals, Butterflies/anatomy \& histology/genetics, Melanins/metabolism, Pigmentation/*genetics, Wing/anatomy \& histology}, isbn = {1755-148X (Electronic)1755-1471 (Linking)}, author = {Kronforst, M. R. and Barsh, G. S. and Kopp, A. and Mallet, J. and Monteiro, A. and Mullen, S. P. and Protas, M. and Rosenblum, E. B. and Schneider, C. J. and Hoekstra, HE} } @article {597966, title = {Striking coat colour variation in tuco-tucos (Rodentia: Ctenomyidae): A role for the melanocortin-1 receptor?}, journal = {Biological Journal of the Linnean Society}, volume = {105}, year = {2011}, pages = {665-80}, abstract = {

South American tuco-tucos (Ctenomys) are characterized by striking variation in coat colour. A range of phenotypes, from pale blonde to dark black, is observed across species, with some of them matching their local substrate colour. Moreover, phenotypic convergence is evident in some taxa that occupy similar habitats. The present study investigated a role for the melanocortin-1 receptor (Mc1r) in determining coat-colour variation in a wide range of Ctenomys species. We sequenced 1250 bp, including the entire Mc1r coding region and a portion of the adjacent 5'\ and 3' untranslated regions, in 21 species. In total, 20 amino acid replacements were identified in Mc1r. However, our findings suggest that these changes have not contributed to coat-colour differences among tuco-tucos because no amino acid replacement was associated with pigmentation phenotype in a simple way. Levels of Mc1r expression were measured in skin samples from dorsal, flank, and ventral body regions in pale, brown, and melanic individuals. We did not observe any significant difference in transcript abundance among phenotypes, although we identified a significant reduction of expression level from the dorsal to ventral region in both pale and brown morphs but not in the completely melanic form. Thus, a role for Mc1r regulation in tuco-tucos colour pattern cannot be completely ruled out, although further functional assays are needed. Finally, selection analysis suggests that Mc1r, in a majority of lineages, has evolved under purifying selection but with relaxation in functional constraint in some regions, especially in the fourth transmembrane domain. In summary, the results obtained in the present study suggest that this trait may have a complex basis, and that other pigmentation genes are involved in generating the dramatic diversity in coat-colour phenotypes observed among Ctenomys species. {\textcopyright} 2012 The Linnean Society of London, Biological Journal of the Linnean Society, 2012, 105, 665{\textendash}680.

}, author = {Goncalves, G. and Hoekstra, HE and T.R.O. de Freitas.} } @article {549371, title = {The developmental role of Agouti in color pattern evolution}, journal = {Science}, volume = {331}, number = {6020}, year = {2011}, note = {

Manceau, MarieDomingues, Vera SMallarino, RicardoHoekstra, Hopi EengResearch Support, Non-U.S. Gov{\textquoteright}tResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.New York, N.Y.2011/02/26 06:00Science. 2011 Feb 25;331(6020):1062-5. doi: 10.1126/science.1200684.

}, month = {Feb 25}, pages = {1062-5}, abstract = {

Animal color patterns can affect fitness in the wild; however, little is known about the mechanisms that control their formation and subsequent evolution. We took advantage of two locally camouflaged populations of Peromyscus mice to show that the negative regulator of adult pigmentation, Agouti, also plays a key developmental role in color pattern evolution. Genetic and functional analyses showed that ventral-specific embryonic expression of Agouti establishes a prepattern by delaying the terminal differentiation of ventral melanocytes. Moreover, a skin-specific increase in both the level and spatial domain of Agouti expression prevents melanocyte maturation in a regionalized manner, resulting in a novel and adaptive color pattern. Thus, natural selection favors late-acting, tissue-specific changes in embryonic Agouti expression to produce large changes in adult color pattern.

}, keywords = {*Biological Evolution, *Gene Expression Regulation, Developmental, Agouti Signaling Protein/*genetics/metabolism, Alleles, Animals, Body Patterning, Cell Differentiation, Cell Proliferation, Dermis/cytology/embryology/metabolism, Embryo, Mammalian, Epidermis/cytology/embryology/metabolism, Female, Fetus, Gene Expression, Hair Color/*genetics, Hair Follicle/cytology/embryology/metabolism, Male, Melanocytes/*cytology/physiology, Mutation, Peromyscus/*embryology/*genetics, Skin/cytology/*embryology/metabolism}, isbn = {1095-9203 (Electronic)0036-8075 (Linking)}, author = {Manceau, M. and Domingues, V. S. and Mallarino, R. and Hoekstra, HE} } @article {549206, title = {Molecular spandrels: Tests of adaptation at the genetic level}, journal = {Nature Reviews Genetics}, volume = {12}, number = {11}, year = {2011}, note = {

Barrett, Rowan D HHoekstra, Hopi EengResearch Support, Non-U.S. Gov{\textquoteright}tResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.ReviewEngland2011/10/19 06:00Nat Rev Genet. 2011 Oct 18;12(11):767-80. doi: 10.1038/nrg3015.

}, month = {Nov}, pages = {767-80}, abstract = {

Although much progress has been made in identifying the genes (and, in rare cases, mutations) that contribute to phenotypic variation, less is known about the effects that these genes have on fitness. Nonetheless, genes are commonly labelled as {\textquoteright}adaptive{\textquoteright} if an allele has been shown to affect a phenotype with known or suspected functional importance or if patterns of nucleotide variation at the locus are consistent with positive selection. In these cases, the {\textquoteright}adaptive{\textquoteright} designation may be premature and may lead to incorrect conclusions about the relationships between gene function and fitness. Experiments to test targets and agents of natural selection within a genomic context are necessary for identifying the adaptive consequences of individual alleles.

}, keywords = {*Genetic Variation, Adaptation, Physiological/*genetics, Alleles, Animals, genome, Genotype, Humans, Linkage Disequilibrium, Phenotype, Quantitative Trait Loci, Selection, Genetic}, isbn = {1471-0064 (Electronic)1471-0056 (Linking)}, author = {Barrett, R. D. and Hoekstra, HE} } @article {597991, title = {Empowering 21st century biology}, journal = {BioScience}, volume = {60}, year = {2010}, pages = {923-30}, abstract = {

Several lists of grand challenges in biology have been published recently, highlighting the strong need to answer fundamental questions about how\ life evolves and is governed, and how to apply this knowledge to solve the pressing problems of our times. To succeed in addressing the challenges\ of 21st century biology, scientists need to generate, have access to, interpret, and archive more information than ever before. But for many\ important questions in biology, progress is stymied by a lack of essential tools. Discovering and developing necessary tools requires new technologies,\ applications of existing technologies, software, model organisms, and social structures. Such new social structures will promote tool building,\ tool sharing, research collaboration, and interdisciplinary training. Here we identify examples of the some of the most important needs for\ addressing critical questions in biology and making important advances in the near future.

}, author = {Robinson, G.E. and JA Banks and DK Padilla and WW Burggren and CS Cohen and CF Delwiche and V Funk and Hoekstra, HE and ED Jarvis and L Johnson and M.Q. Martindale and C Martinez del Rio and Medina, M. and DE Salt and S Sinha and C Specht and K Strange and Strassmann, J. E. and BJ Swalla and L Tomanek} } @inbook {597981, title = {Evolutionary Biology: The Next 150 years}, booktitle = {Evolution Since Darwin: The First 150 Years.}, year = {2010}, publisher = {Sinauer Press}, organization = {Sinauer Press}, address = {Sunderland, MA}, author = {Hoekstra, HE}, editor = {M.A. Bell and D.A. Futuyma and W.F. Eanes and J.S. Levinton} } @inbook {597976, title = {From Darwin to DNA: The genetic basis of color adaptation}, booktitle = {In the Light of Evolution: Essays from the Laboratory and Field}, year = {2010}, publisher = {Roberts and Co. Publishers}, organization = {Roberts and Co. Publishers}, address = {Greenwood Village, CO}, author = {Hoekstra, HE}, editor = {Losos, J. B.} } @inbook {597971, title = {In search of the elusive behavior gene}, booktitle = {Search for the Causes of Evolution: From Field Observations to Mechanisms}, year = {2010}, publisher = {Princeton University Press}, organization = {Princeton University Press}, address = {Princeton, NJ}, author = {Hoekstra, HE}, editor = {P. Grant and R. Grant} } @article {549231, title = {Competition drives cooperation among closely related sperm of deer mice}, journal = {Nature }, volume = {463}, number = {7282}, year = {2010}, note = {

Fisher, Heidi SHoekstra, Hopi EengF32 GM084719/GM/NIGMS NIH HHS/F32 GM084719-02/GM/NIGMS NIH HHS/Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov{\textquoteright}tEngland2010/01/22 06:00Nature. 2010 Feb 11;463(7282):801-3. doi: 10.1038/nature08736. Epub 2010 Jan 20.

Featured on\ NPR\ talk and\ Current Biology\ Dispatch

Paper selected by Faculty of 1000

}, month = {Feb 11}, pages = {801-3}, abstract = {

Among the extraordinary adaptations driven by sperm competition is the cooperative behaviour of spermatozoa. By forming cooperative groups, sperm can increase their swimming velocity and thereby gain an advantage in intermale sperm competition. Accordingly, selection should favour cooperation of the most closely related sperm to maximize fitness. Here we show that sperm of deer mice (genus Peromyscus) form motile aggregations, then we use this system to test predictions of sperm cooperation. We find that sperm aggregate more often with conspecific than heterospecific sperm, suggesting that individual sperm can discriminate on the basis of genetic relatedness. Next, we provide evidence that the cooperative behaviour of closely related sperm is driven by sperm competition. In a monogamous species lacking sperm competition, Peromyscus polionotus, sperm indiscriminately group with unrelated conspecific sperm. In contrast, in the highly promiscuous deer mouse, Peromyscus maniculatus, sperm are significantly more likely to aggregate with those obtained from the same male than with sperm from an unrelated conspecific donor. Even when we test sperm from sibling males, we continue to see preferential aggregations of related sperm in P. maniculatus. These results suggest that sperm from promiscuous deer mice discriminate among relatives and thereby cooperate with the most closely related sperm, an adaptation likely to have been driven by sperm competition.

}, keywords = {*Cooperative Behavior, Animals, Cell Aggregation, Competitive Behavior/*physiology, Copulation/physiology, Female, Male, Peromyscus/*classification/*physiology, Sexual Behavior, Animal/*physiology, Species Specificity, Sperm Motility/physiology, Spermatozoa/*physiology}, isbn = {1476-4687 (Electronic)0028-0836 (Linking)}, author = {Fisher, H. S. and Hoekstra, HE} } @article {549366, title = {Convergence in pigmentation at multiple levels: mutations, genes and function}, journal = {Philosophical Transactions of the Royal Society}, volume = {365}, number = {1552}, year = {2010}, note = {

Manceau, MarieDomingues, Vera SLinnen, Catherine RRosenblum, Erica BreeHoekstra, Hopi EengResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov{\textquoteright}tResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.England2010/07/21 06:00Philos Trans R Soc Lond B Biol Sci. 2010 Aug 27;365(1552):2439-50. doi: 10.1098/rstb.2010.0104.

}, month = {Aug 27}, pages = {2439-50}, abstract = {

Convergence--the independent evolution of the same trait by two or more taxa--has long been of interest to evolutionary biologists, but only recently has the molecular basis of phenotypic convergence been identified. Here, we highlight studies of rapid evolution of cryptic coloration in vertebrates to demonstrate that phenotypic convergence can occur at multiple levels: mutations, genes and gene function. We first show that different genes can be responsible for convergent phenotypes even among closely related populations, for example, in the pale beach mice inhabiting Florida{\textquoteright}s Gulf and Atlantic coasts. By contrast, the exact same mutation can create similar phenotypes in distantly related species such as mice and mammoths. Next, we show that different mutations in the same gene need not be functionally equivalent to produce similar phenotypes. For example, separate mutations produce divergent protein function but convergent pale coloration in two lizard species. Similarly, mutations that alter the expression of a gene in different ways can, nevertheless, result in similar phenotypes, as demonstrated by sister species of deer mice. Together these studies underscore the importance of identifying not only the genes, but also the precise mutations and their effects on protein function, that contribute to adaptation and highlight how convergence can occur at different genetic levels.

}, keywords = {*Biological Evolution, *Phenotype, *Selection, Genetic, Adaptation, Biological/*genetics, Agouti Signaling Protein/genetics, Animals, Florida, Lizards, Mice, Mutation/genetics, New Mexico, Pigmentation/*genetics, Receptor, Melanocortin, Type 1/genetics}, isbn = {1471-2970 (Electronic)0962-8436 (Linking)}, author = {Manceau, M. and Domingues, V. S. and Linnen, C. R. and Rosenblum, E. B. and Hoekstra, HE} } @article {549466, title = {Five hundred microsatellite loci for Peromyscus}, journal = {Conservation Genetics}, volume = {11}, number = {3}, year = {2010}, note = {

Weber, Jesse NPeters, Maureen BTsyusko, Olga VLinnen, Catherine RHagen, CrisSchable, Nancy ATuberville, Tracey DMcKee, Anna MLance, Stacey LJones, Kenneth LFisher, Heidi SDewey, Michael JHoekstra, Hopi EGlenn, Travis CENGF32 GM083073-02/GM/NIGMS NIH HHS/P40 RR014279-06/RR/NCRR NIH HHS/R01 GM069601-02/GM/NIGMS NIH HHS/Print2010/06/22 06:00Conserv Genet. 2010 Jun 1;11(3):1243-1246.

}, month = {Jun 1}, pages = {1243-46}, abstract = {

Mice of the genus Peromyscus, including several endangered subspecies, occur throughout North America and have been important models for conservation research. We describe 526 primer pairs that amplify microsatellite DNA loci for P. maniculatus bairdii, 467 of which also amplify in P. polionotus subgriseus. For 12 of these loci, we report diversity data from a natural population. These markers will be an important resource for future genomic studies of Peromyscus evolution and mammalian conservation.

}, isbn = {1566-0621 (Print)1566-0621 (Linking)}, author = {Weber, J. N. and Peters, M. B. and Tsyusko, O. V. and Linnen, C. R. and Hagen, C. and Schable, N. A. and Tuberville, T. D. and McKee, A. M. and Lance, S. L. and Jones, K. L. and Fisher, H. S. and Dewey, M. J. and Hoekstra, HE and Glenn, T. C.} } @article {549211, title = {Maternal-fetal conflict: Rapidly evolving proteins in the rodent placenta}, journal = {Molecular Biology and Evolution }, volume = {27}, number = {6}, year = {2010}, note = {

Chuong, Edward BTong, WenfeiHoekstra, Hopi EengT32 HG000044/HG/NHGRI NIH HHS/LetterResearch Support, Non-U.S. Gov{\textquoteright}t2010/02/04 06:00Mol Biol Evol. 2010 Jun;27(6):1221-5. doi: 10.1093/molbev/msq034. Epub 2010 Feb 1.

}, month = {Jun}, pages = {1221-5}, abstract = {

Conflicting evolutionary interests between mother and offspring are hypothesized to drive an evolutionary arms race during mammalian pregnancy, and thus, positive selection may cause the rapid divergence of placental proteins that affect maternal or fetal fitness. We investigated the genomic consequences of placental expression in rodents and report that a substantial proportion (20.5\%) of genes specifically expressed in the mature placenta are rapidly evolving. Moreover, we found that most rapidly evolving genes belong to just three pregnancy-related gene families: placental cathepsins, prolactins, and placental carcinoembryonic antigens. We then sequenced the most rapidly evolving gene, trophoblast-specific protein alpha (Tpbpa), in nine different Mus species/subspecies and found evidence of positive selection within the Mus lineage, with an excess of nonsynonymous changes clustering near a functionally important interaction site. Together, these results suggest that placental proteins, which mediate interactions between mother and offspring, often may be the targets of evolutionary conflict.

}, keywords = {Adaptation, Physiological, Amino Acid Sequence, Analysis of Variance, Animals, Cathepsins/genetics/metabolism, Female, Humans, Maternal-Fetal Exchange/genetics/*physiology, Molecular Sequence Data, Phylogeny, Placenta/*metabolism, Pregnancy, Pregnancy Proteins/genetics/*metabolism, Prolactin/genetics/metabolism, Rats, Selection, Genetic}, isbn = {1537-1719 (Electronic)0737-4038 (Linking)}, author = {Chuong, E. B. and Tong, W. and Hoekstra, HE} } @article {549346, title = {Measuring natural selection on genotypes and phenotypes in the wild}, journal = {Cold Spring Harbor Symposia on Quantitative Biology}, volume = {74}, year = {2010}, note = {

Linnen, C RHoekstra, H EengF32 GM083073/GM/NIGMS NIH HHS/Research Support, Non-U.S. Gov{\textquoteright}tResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.Review2010/04/24 06:00Cold Spring Harb Symp Quant Biol. 2009;74:155-68. doi: 10.1101/sqb.2009.74.045. Epub 2010 Apr 22.

}, pages = {155-68}, abstract = {

A complete understanding of the role of natural selection in driving evolutionary change requires accurate estimates of the strength of selection acting in the wild. Accordingly, several approaches using a variety of data-including patterns of DNA variability, spatial and temporal changes in allele frequencies, and fitness estimates-have been developed to identify and quantify selection on both genotypes and phenotypes. Here, we review these approaches, drawing on both recent and classic examples to illustrate their utility and limitations. We then argue that by combining estimates of selection at multiple levels-from individual mutations to phenotypes-and at multiple timescales-from ecological to evolutionary-with experiments that demonstrate why traits are under selection, we can gain a much more complete picture of the adaptive process.

}, keywords = {*Models, Genetic, *Selection, Genetic, Alleles, Animals, Biological Evolution, DNA/genetics, Gene Frequency, Genotype, Peromyscus/genetics, Phenotype, Smegmamorpha/genetics}, isbn = {1943-4456 (Electronic)0091-7451 (Linking)}, author = {Linnen, C. R. and Hoekstra, HE} } @article {549416, title = {Molecular and functional basis of phenotypic convergence in white lizards at White Sands}, journal = {PNAS}, volume = {107}, number = {5}, year = {2010}, note = {

Rosenblum, Erica BreeRompler, HolgerSchoneberg, TorstenHoekstra, Hopi EengResearch Support, Non-U.S. Gov{\textquoteright}t2010/01/19 06:00Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):2113-7. doi: 10.1073/pnas.0911042107. Epub 2009 Dec 28.

PNAS

Papers selected by Faculty of 1000

}, month = {Feb 2}, pages = {2113-7}, abstract = {

There are many striking examples of phenotypic convergence in nature, in some cases associated with changes in the same genes. But even mutations in the same gene may have different biochemical properties and thus different evolutionary consequences. Here we dissect the molecular mechanism of convergent evolution in three lizard species with blanched coloration on the gypsum dunes of White Sands, New Mexico. These White Sands forms have rapidly evolved cryptic coloration in the last few thousand years, presumably to avoid predation. We use cell-based assays to demonstrate that independent mutations in the same gene underlie the convergent blanched phenotypes in two of the three species. Although the same gene contributes to light phenotypes in these White Sands populations, the specific molecular mechanisms leading to reduced melanin production are different. In one case, mutations affect receptor signaling and in the other, the ability of the receptor to integrate into the melanocyte membrane. These functional differences have important ramifications at the organismal level. Derived alleles in the two species show opposite dominance patterns, which in turn affect their visibility to selection and the spatial distribution of alleles across habitats. Our results demonstrate that even when the same gene is responsible for phenotypic convergence, differences in molecular mechanism can have dramatic consequences on trait expression and ultimately the adaptive trajectory.

}, keywords = {*Evolution, Molecular, Adaptation, Physiological/genetics, Alleles, Amino Acid Substitution, Animals, Ecosystem, Genes, Dominant, Genetics, Population, Lizards/classification/*genetics/*physiology, Melanins/biosynthesis, Mutation, New Mexico, Receptor, Melanocortin, Type 1/genetics, Silicon Dioxide, Skin Pigmentation/*genetics/*physiology, Soil, Species Specificity}, isbn = {1091-6490 (Electronic)0027-8424 (Linking)}, author = {Rosenblum, E. B. and Rompler, H. and Schoneberg, T. and Hoekstra, HE} } @article {549456, title = {Monogamy evolves through multiple mechanisms: Evidence from V1aR in deer mice}, journal = {Molecular Biology and Evolution}, volume = {27}, number = {6}, year = {2010}, note = {

Turner, Leslie MYoung, Adrian RRompler, HolgerSchoneberg, TorstenPhelps, Steven MHoekstra, Hopi EengResearch Support, Non-U.S. Gov{\textquoteright}tResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.2010/01/26 06:00Mol Biol Evol. 2010 Jun;27(6):1269-78. doi: 10.1093/molbev/msq013. Epub 2010 Jan 22.

}, month = {Jun}, pages = {1269-78}, abstract = {

Genetic variation in Avpr1a, the locus encoding the arginine vasopressin receptor 1A (V1aR), has been implicated in pair-bonding behavior in voles (genus Microtus) and humans, raising the possibility that this gene may contribute commonly to mating-system variation in mammals. In voles, differential expression of V1aR in the brain is associated with male partner-preference behavior in a comparison of a monogamous (Microtus ochrogaster) and promiscuous (Microtus montanus) species. This expression difference is correlated, in turn, with a difference in length of a 5{\textquoteright} regulatory microsatellite in Avpr1a. Here, we use a combination of comparative sequencing of coding and regulatory regions, analysis of neural expression patterns, and signaling assays to test for differences in V1aR expression and function among eight species of deer mice (genus Peromyscus). Despite well-documented variation in Peromyscus social behavior, we find no association between mating system and length variation in the microsatellite locus linked to V1aR expression in voles. Further, there are no consistent differences in V1aR expression pattern between monogamous and promiscuous species in regions of the brain known to influence mating behavior. We do find statistical evidence for positive selection on the V1aR coding sequence including several derived amino acid substitutions in a monogamous Peromyscus lineage, yet these substitutions have no measurable effect on V1aR signaling activity. Together, these results suggest that mating-system variation in rodents is mediated by multiple genetic mechanisms.

}, keywords = {*Models, Genetic, *Pair Bond, Amino Acid Sequence, Animals, Brain/metabolism, Female, Histocytochemistry, Male, Microsatellite Repeats, Molecular Sequence Data, Organ Specificity, Peromyscus/*genetics, Phylogeny, Polymorphism, Genetic, Receptors, Vasopressin/*genetics/metabolism, Signal Transduction/genetics, Species Specificity, Vasopressins/metabolism}, isbn = {1537-1719 (Electronic)0737-4038 (Linking)}, author = {Turner, L. M. and Young, A. R. and Rompler, H. and Schoneberg, T. and Phelps, S. M. and Hoekstra, HE} } @article {549301, title = {Population structure and plumage polymorphism: The intraspecific evolutionary relationships of a polymorphic raptor, Buteo jamaicensis harlani}, journal = {BMC Evolutionary Biology}, volume = {10}, year = {2010}, note = {

Hull, Joshua MMindell, David PTalbot, Sandra LKay, Emily HHoekstra, Hopi EErnest, Holly BengResearch Support, Non-U.S. Gov{\textquoteright}tResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.England2010/07/24 06:00BMC Evol Biol. 2010 Jul 22;10:224. doi: 10.1186/1471-2148-10-224.

}, pages = {224}, abstract = {

BACKGROUND: Phenotypic and molecular genetic data often provide conflicting patterns of intraspecific relationships confounding phylogenetic inference, particularly among birds where a variety of environmental factors may influence plumage characters. Among diurnal raptors, the taxonomic relationship of Buteo jamaicensis harlani to other B. jamaicensis subspecies has been long debated because of the polytypic nature of the plumage characteristics used in subspecies or species designations. RESULTS: To address the evolutionary relationships within this group, we used data from 17 nuclear microsatellite loci, 430 base pairs of the mitochondrial control region, and 829 base pairs of the melanocortin 1 receptor (Mc1r) to investigate molecular genetic differentiation among three B. jamaicensis subspecies (B. j. borealis, B. j. calurus, B. j. harlani). Bayesian clustering analyses of nuclear microsatellite loci showed no significant differences between B. j. harlani and B. j. borealis. Differences observed between B. j. harlani and B. j. borealis in mitochondrial and microsatellite data were equivalent to those found between morphologically similar subspecies, B. j. borealis and B. j. calurus, and estimates of migration rates among all three subspecies were high. No consistent differences were observed in Mc1r data between B. j. harlani and other B. jamaicensis subspecies or between light and dark color morphs within B. j. calurus, suggesting that Mc1r does not play a significant role in B. jamaicensis melanism. CONCLUSIONS: These data suggest recent interbreeding and gene flow between B. j. harlani and the other B. jamaicensis subspecies examined, providing no support for the historical designation of B. j. harlani as a distinct species.

}, keywords = {*Evolution, Molecular, *Gene Flow, *Phylogeny, *Polymorphism, Genetic, Animals, Bayes Theorem, Cell Nucleus/genetics, Cluster Analysis, DNA, Mitochondrial/genetics, Feathers/physiology, Geography, Microsatellite Repeats, Models, Genetic, Raptors/*genetics, Receptor, Melanocortin, Type 1/genetics, Sequence Analysis, DNA, Species Specificity}, isbn = {1471-2148 (Electronic)1471-2148 (Linking)}, author = {Hull, J. M. and Mindell, D. P. and Talbot, S. L. and Kay, E. H. and Hoekstra, HE and Ernest, H. B.} } @article {549461, title = {The selective advantage of crypsis in mice}, journal = {Evolution}, volume = {64}, number = {7}, year = {2010}, note = {

Vignieri, Sacha NLarson, Joanna GHoekstra, Hopi EengResearch Support, Non-U.S. Gov{\textquoteright}tResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.2010/02/19 06:00Evolution. 2010 Jul;64(7):2153-8. doi: 10.1111/j.1558-5646.2010.00976.x. Epub 2010 Jan 15.

}, month = {Jul}, pages = {2153-8}, abstract = {

The light color of mice that inhabit the sandy dunes of Florida{\textquoteright}s coast have served as a textbook example of adaptation for nearly a century, despite the fact that the selective advantage of crypsis has never been directly tested or quantified in nature. Using plasticine mouse models of light and dark color, we demonstrate a strong selective advantage for mice that match their local background substrate. Further our data suggest that stabilizing selection maintains color matching within a single habitat, as models that are both lighter and darker than their local environment are selected against. These results provide empirical evidence in support of the hypothesis that visual hunting predators shape color patterning in Peromyscus mice and suggest a mechanism by which selection drives the pronounced color variation among populations.

}, keywords = {*Ecosystem, *Selection, Genetic, Adaptation, Biological/*physiology, Animals, Color, Florida, Models, Anatomic, Peromyscus/*physiology, Pigmentation/*physiology, Predatory Behavior/physiology}, isbn = {1558-5646 (Electronic)0014-3820 (Linking)}, author = {Vignieri, S. N. and Larson, J. G. and Hoekstra, HE} } @article {549376, title = {Turing patterns: How the fish got its spots}, journal = {Pigment Cell \& Melanoma Research}, volume = {24}, number = {1}, year = {2010}, note = {

Metz, Hillery CManceau, MarieHoekstra, Hopi EengNewsEngland2010/12/02 06:00Pigment Cell Melanoma Res. 2011 Feb;24(1):12-4. doi: 10.1111/j.1755-148X.2010.00814.x.

}, month = {Feb}, pages = {12-4}, keywords = {*Models, Biological, Animals, Biological Evolution, Computer Simulation, Diffusion, Fishes/genetics/*physiology, Pigmentation/genetics/*physiology}, isbn = {1755-148X (Electronic)1755-1471 (Linking)}, author = {Metz, H. C. and Manceau, M. and Hoekstra, HE} } @article {549296, title = {Vertebrate pigmentation: From underlying genes to adaptive function}, journal = {Trends in Genetics}, volume = {26}, number = {5}, year = {2010}, note = {

Hubbard, Joanna KUy, J Albert CHauber, Mark EHoekstra, Hopi ESafran, Rebecca JengResearch Support, Non-U.S. Gov{\textquoteright}tResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.ReviewEngland2010/04/13 06:00Trends Genet. 2010 May;26(5):231-9. doi: 10.1016/j.tig.2010.02.002. Epub 2010 Apr 8.

}, month = {May}, pages = {231-9}, abstract = {

Animal coloration is a powerful model for studying the genetic mechanisms that determine phenotype. Genetic crosses of laboratory mice have provided extensive information about the patterns of inheritance and pleiotropic effects of loci involved in pigmentation. Recently, the study of pigmentation genes and their functions has extended into wild populations, providing additional evidence that pigment gene function is largely conserved across disparate vertebrate taxa and can influence adaptive coloration, often in predictable ways. These new and integrative studies, along with those using a genetic approach to understand color perception, raise some important questions. Most notably, how does selection shape both phenotypic and genetic variation, and how can we use this information to further understand the phenotypic diversity generated by evolutionary processes?

}, keywords = {*Biological Evolution, Animals, Color Perception/genetics, Pigmentation/*genetics}, isbn = {0168-9525 (Print)0168-9525 (Linking)}, author = {Hubbard, J. K. and Uy, J. A. and Hauber, M. E. and Hoekstra, HE and Safran, R. J.} } @article {598006, title = {The evolution of burrowing behavior in deer mice}, journal = {Animal Behavior}, volume = {77}, year = {2009}, note = {

Article history:

Received 28 February 2008

Initial acceptance 22 July 2008

Final acceptance 17 October 2008

Published online 1 January 2009

MS. number: A08-00124R

}, pages = {603-09}, abstract = {

The evolutionary history of most behaviours remains unknown. Here, we assay burrowing behaviour of\ seven species of deer mice in standardized environments to determine how burrowing evolved in this\ genus (Peromyscus). We found that several, but not all, species burrow even after many generations of\ captive breeding. Specifically, there were significant and repeatable differences in both the frequency of\ burrowing and burrow shape between species. Moreover, these observed species-specific behaviours\ resemble those reported in wild mice. These results suggest that there is probably a strong genetic\ component to burrowing in deer mice. We also generated a phylogeny for these seven species using\ characters from four mtDNA and two autosomal loci. Mapping burrowing behaviour onto this phylogeny\ suggests a sequence for how complex burrowing evolves: from small, simple burrows to long, multitunnel\ burrows with defined entrance and escape tunnels. In particular, the most {\textquoteleft}complex{\textquoteright} burrows of P.\ polionotus appear to be derived. These behavioural data, when examined in a phylogenetic context, show\ that even closely related species differ in their burrowing behaviours and that the most complex burrows\ probably evolved by the gradual accumulation of genetic change over time.\ 2008 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved.

}, author = {Weber, J. N. and Hoekstra, HE} } @article {597996, title = {The Evolution Ringmaster: Review of The Greatest Show on Earth: The Evidence for Evolution by Richard Dawkins}, journal = {Cell}, volume = {139}, year = {2009}, pages = {454-55}, author = {Hoekstra, HE} } @article {598001, title = {(Re)Reading The Origin}, journal = {Current Biology }, volume = {19}, year = {2009}, pages = {R9}, author = {Berry, A. J. and Hoekstra, HE} } @article {549386, title = {Adaptive basis of geographic variation: Genetic, phenotypic and environmental differences among beach mouse populations}, journal = {Proceedings of the Royal Society B: Biological Sciences}, volume = {276}, number = {1674}, year = {2009}, note = {

Mullen, Lynne MVignieri, Sacha NGore, Jeffery AHoekstra, Hopi EengResearch Support, Non-U.S. Gov{\textquoteright}tResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.England2009/08/07 09:00Proc Biol Sci. 2009 Nov 7;276(1674):3809-18. doi: 10.1098/rspb.2009.1146. Epub 2009 Aug 5.

}, month = {Nov 7}, pages = {3809-18}, abstract = {

A major goal in evolutionary biology is to understand how and why populations differentiate, both genetically and phenotypically, as they invade a novel habitat. A classical example of adaptation is the pale colour of beach mice, relative to their dark mainland ancestors, which colonized the isolated sandy dunes and barrier islands on Florida{\textquoteright}s Gulf Coast. However, much less is known about differentiation among the Gulf Coast beach mice, which comprise five subspecies linearly arrayed on Florida{\textquoteright}s shoreline. Here, we test the role of selection in maintaining variation among these beach mouse subspecies at multiple levels-phenotype, genotype and the environments they inhabit. While all beach subspecies have light pelage, they differ significantly in colour pattern. These subspecies are also genetically distinct: pair-wise F(st)-values range from 0.23 to 0.63 and levels of gene flow are low. However, we did not find a correlation between phenotypic and genetic distance. Instead, we find a significant association between the average {\textquoteright}lightness{\textquoteright} of each subspecies and the brightness of the substrate it inhabits: the two most genetically divergent subspecies occupy the most similar habitats and have converged on phenotype, whereas the most genetically similar subspecies occupy the most different environments and have divergent phenotypes. Moreover, allelic variation at the pigmentation gene, Mc1r, is statistically correlated with these colour differences but not with variation at other genetic loci. Together, these results suggest that natural selection for camouflage-via changes in Mc1r allele frequency-contributes to pigment differentiation among beach mouse subspecies.

}, keywords = {*Adaptation, Physiological, *Ecosystem, *Pigments, Biological, Animals, demography, Florida, Genetic Variation, Peromyscus/*genetics/*physiology, Phenotype, Phylogeny, Silicon Dioxide}, isbn = {0962-8452 (Print)0962-8452 (Linking)}, author = {Mullen, L. M. and Vignieri, S. N. and Gore, J. A. and Hoekstra, HE} } @article {549201, title = {Convergent evolution of novel protein function in shrew and lizard venom}, journal = {Current Biology}, volume = {19}, number = {22}, year = {2009}, note = {

Aminetzach, Yael TSrouji, John RKong, Chung YinHoekstra, Hopi EengResearch Support, Non-U.S. Gov{\textquoteright}tEngland2009/11/03 06:00Curr Biol. 2009 Dec 1;19(22):1925-31. doi: 10.1016/j.cub.2009.09.022. Epub 2009 Oct 29.

Featured in\ Current Biology

Paper selected by Faculty of 1000

}, month = {Dec 1}, pages = {1925-31}, abstract = {

How do proteins evolve novel functions? To address this question, we are studying the evolution of a mammalian toxin, the serine protease BLTX [1], from the salivary glands of the North American shrew Blarina brevicauda. Here, we examine the molecular changes responsible for promoting BLTX toxicity. First, we show that regulatory loops surrounding the BLTX active site have evolved adaptively via acquisition of small insertions and subsequent accelerated sequence evolution. Second, these mutations introduce a novel chemical environment into the catalytic cleft of BLTX. Third, molecular-dynamic simulations show that the observed changes create a novel chemical and physical topology consistent with increased enzyme catalysis. Finally, we show that a toxic serine protease from the Mexican beaded lizard (GTX) [2] has evolved convergently through almost identical functional changes. Together, these results suggest that the evolution of toxicity might be predictable-arising via adaptive structural modification of analogous labile regulatory loops of an ancestral serine protease-and thus might aid in the identification of other toxic proteins.

}, keywords = {Amino Acid Sequence, Animals, Biocatalysis, Lizards, Models, Molecular, Molecular Sequence Data, Sequence Homology, Amino Acid, Shrews, Venoms/chemistry/*genetics/toxicity}, isbn = {1879-0445 (Electronic)0960-9822 (Linking)}, author = {Aminetzach, Y. T. and Srouji, J. R. and Kong, C. Y. and Hoekstra, HE} } @article {549421, title = {The genetic basis of phenotypic convergence in beach mice: Similar pigment patterns but different genes}, journal = {Molecular Biology and Evolution}, volume = {26}, number = {1}, year = {2009}, note = {

Steiner, Cynthia CRompler, HolgerBoettger, Linda MSchoneberg, TorstenHoekstra, Hopi EengResearch Support, Non-U.S. Gov{\textquoteright}tResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.2008/10/04 09:00Mol Biol Evol. 2009 Jan;26(1):35-45. doi: 10.1093/molbev/msn218. Epub 2008 Oct 1.

}, month = {Jan}, pages = {35-45}, abstract = {

Convergent evolution is a widespread phenomenon seen in diverse organisms inhabiting similar selective environments. However, it is unclear if similar phenotypes are produced by the same or different genes and mutations. Here we analyze the molecular mechanisms underlying convergent pigment pattern among subspecies of the beach mouse (Peromyscus polionotus) inhabiting the Gulf and Atlantic coasts of Florida. In these two geographic regions, separated by more than 300 km, "beach mice" have lighter colored coats than do their mainland counterparts, produced by natural selection for camouflage against the pale coastal sand dunes. We measured color pattern in eight beach mouse subspecies and showed that three of the Gulf Coast subspecies are more phenotypically similar to an Atlantic coast subspecies than to their Gulf Coast neighbors. However, light-colored beach mice do not form a monophyletic group. Previous results implicated a single derived amino acid change in the melanocortin-1 receptor (Mc1r) as a major contributor to pigment pattern in the Gulf Coast beach mice; despite phenotypic similarities, the derived Mc1r allele was not found in the Atlantic coast beach mouse populations. Here we show that Atlantic coast beach mice have high levels of Mc1r polymorphism but they lack unique alleles. Functional assays revealed that single amino acid mutations segregating in Atlantic coast beach mice do not cause any change in Mc1r activity compared with the activity of Mc1r from dark-colored mice. These joint results show that convergent pigment patterns in recently diverged beach mouse subspecies--whose developmental constraints are presumably similar--have evolved through a diversity of genetic mechanisms.

}, keywords = {Animals, DNA, Mitochondrial/genetics, Environment, Florida, Genetic Variation, Molecular Sequence Data, Peromyscus/classification/*genetics, Pigmentation/*genetics, Polymorphism, Single Nucleotide, Receptor, Melanocortin, Type 1/*genetics, Selection, Genetic, United States}, isbn = {1537-1719 (Electronic)0737-4038 (Linking)}, author = {Steiner, C. C. and Rompler, H. and Boettger, L. M. and Schoneberg, T. and Hoekstra, HE} } @article {549311, title = {Melanism in Peromyscus is caused by independent mutations in Agouti}, journal = {PLoS One}, volume = {4}, number = {7}, year = {2009}, note = {

Kingsley, Evan PManceau, MarieWiley, Christopher DHoekstra, Hopi EengResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.2009/08/04 09:00PLoS One. 2009 Jul 30;4(7):e6435. doi: 10.1371/journal.pone.0006435.

}, pages = {e6435}, abstract = {

Identifying the molecular basis of phenotypes that have evolved independently can provide insight into the ways genetic and developmental constraints influence the maintenance of phenotypic diversity. Melanic (darkly pigmented) phenotypes in mammals provide a potent system in which to study the genetic basis of naturally occurring mutant phenotypes because melanism occurs in many mammals, and the mammalian pigmentation pathway is well understood. Spontaneous alleles of a few key pigmentation loci are known to cause melanism in domestic or laboratory populations of mammals, but in natural populations, mutations at one gene, the melanocortin-1 receptor (Mc1r), have been implicated in the vast majority of cases, possibly due to its minimal pleiotropic effects. To investigate whether mutations in this or other genes cause melanism in the wild, we investigated the genetic basis of melanism in the rodent genus Peromyscus, in which melanic mice have been reported in several populations. We focused on two genes known to cause melanism in other taxa, Mc1r and its antagonist, the agouti signaling protein (Agouti). While variation in the Mc1r coding region does not correlate with melanism in any population, in a New Hampshire population, we find that a 125-kb deletion, which includes the upstream regulatory region and exons 1 and 2 of Agouti, results in a loss of Agouti expression and is perfectly associated with melanic color. In a second population from Alaska, we find that a premature stop codon in exon 3 of Agouti is associated with a similar melanic phenotype. These results show that melanism has evolved independently in these populations through mutations in the same gene, and suggest that melanism produced by mutations in genes other than Mc1r may be more common than previously thought.

}, keywords = {*Mutation, Agouti Signaling Protein/*genetics, Animals, Chromosomes, Artificial, Bacterial, Genes, Recessive, In Situ Hybridization, Melanosis/*genetics, Peromyscus/*genetics, Polymerase Chain Reaction, Receptor, Melanocortin, Type 1/genetics, Sequence Deletion, Species Specificity}, isbn = {1932-6203 (Electronic)1932-6203 (Linking)}, author = {Kingsley, E. P. and Manceau, M. and Wiley, C. D. and Hoekstra, HE} } @article {549351, title = {On the origin and spread of an adaptive allele in deer mice}, journal = {Science}, volume = {325}, number = {5944}, year = {2009}, note = {

Linnen, Catherine RKingsley, Evan PJensen, Jeffrey DHoekstra, Hopi EengF32 GM083073-02/GM/NIGMS NIH HHS/Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov{\textquoteright}tResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.New York, N.Y.2009/08/29 09:00Science. 2009 Aug 28;325(5944):1095-8. doi: 10.1126/science.1175826.

Paper selected by Faculty of 1000

}, month = {Aug 28}, pages = {1095-8}, abstract = {

Adaptation is a central focus of biology, although it can be difficult to identify both the strength and agent of selection and the underlying molecular mechanisms causing change. We studied cryptically colored deer mice living on the Nebraska Sand Hills and show that their light coloration stems from a novel banding pattern on individual hairs produced by an increase in Agouti expression caused by a cis-acting mutation (or mutations), which either is or is closely linked to a single amino acid deletion in Agouti that appears to be under selection. Furthermore, our data suggest that this derived Agouti allele arose de novo after the formation of the Sand Hills. These findings reveal one means by which genetic, developmental, and evolutionary mechanisms can drive rapid adaptation under ecological pressure.

}, keywords = {*Alleles, *Evolution, Molecular, Adaptation, Physiological/*genetics, Agouti Signaling Protein/chemistry/*genetics, Animals, Crosses, Genetic, Ecosystem, Gene Frequency, Hair Color/*genetics, Hair/chemistry/growth \& development, Haplotypes, Linkage Disequilibrium, Melanins/analysis, Molecular Sequence Data, Mutation, Nebraska, Peromyscus/*genetics/physiology, Phenotype, Pigmentation/*genetics, Polymorphism, Genetic, RNA, Messenger/genetics/metabolism, Selection, Genetic, Sequence Deletion, Serine/genetics}, isbn = {1095-9203 (Electronic)0036-8075 (Linking)}, author = {Linnen, C. R. and Kingsley, E. P. and Jensen, J. D. and Hoekstra, HE} } @article {549496, title = {Are we there yet? Tracking the development of new model systems}, journal = {Trends in Genetics}, volume = {24}, number = {7}, year = {2008}, note = {

Abzhanov, ArhatExtavour, Cassandra GGroover, AndrewHodges, Scott AHoekstra, Hopi EKramer, Elena MMonteiro, AntoniaengReviewEngland2008/06/03 09:00Trends Genet. 2008 Jul;24(7):353-60. doi: 10.1016/j.tig.2008.04.002.

}, month = {Jul}, pages = {353-60}, abstract = {

It is increasingly clear that additional {\textquoteright}model{\textquoteright} systems are needed to elucidate the genetic and developmental basis of organismal diversity. Whereas model system development previously required enormous investment, recent advances including the decreasing cost of DNA sequencing and the power of reverse genetics to study gene function are greatly facilitating the process. In this review, we consider two aspects of the development of new genetic model systems: first, the types of questions being advanced using these new models; and second, the essential characteristics and molecular tools for new models, depending on the research focus. We hope that researchers will be inspired to explore this array of emerging models and even consider developing new molecular tools for their own favorite organism.

}, keywords = {*Models, Biological, *Models, Genetic, Animals, Research}, isbn = {0168-9525 (Print)0168-9525 (Linking)}, author = {Abzhanov, A. and Extavour, C. G. and Groover, A. and Hodges, S. A. and Hoekstra, HE and Kramer, E. M. and Monteiro, A.} } @article {549446, title = {Causes and consequences of the evolution of reproductive proteins}, journal = {The International Journal of Developmental Biology}, volume = {52}, number = {5-6}, year = {2008}, note = {

Turner, Leslie MHoekstra, Hopi EengHoward Hughes Medical Institute/Research Support, Non-U.S. Gov{\textquoteright}tResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.ReviewSpain2008/07/24 09:00Int J Dev Biol. 2008;52(5-6):769-80. doi: 10.1387/ijdb.082577lt.

}, pages = {769-80}, abstract = {

Proteins involved in reproduction often evolve rapidly, raising the possibility that changes in these proteins contribute to reproductive isolation between species. We review the evidence for rapid and adaptive change in reproductive proteins in animals, focusing on studies in recently diverged vertebrates. We identify common patterns and point out promising directions for future research. In particular, we highlight the ways that integrating the different but complementary approaches of evolutionary and developmental biology will provide new insights into fertilization processes.

}, keywords = {*Biological Evolution, *Fertilization, *Genetic Speciation, Amino Acid Sequence, Animals, Developmental Biology/*methods, Female, Germ Cells, Humans, Male, Mice, Models, Biological, Models, Theoretical, Molecular Sequence Data, Reproduction}, isbn = {0214-6282 (Print)0214-6282 (Linking)}, author = {Turner, L. M. and Hoekstra, HE} } @article {549431, title = {Combining population genomics and quantitative genetics: Finding the genes underlying ecologically important traits}, journal = {Heredity}, volume = {100}, number = {2}, year = {2008}, note = {

Stinchcombe, J RHoekstra, H EengResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov{\textquoteright}tResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.ReviewEngland2007/02/23 09:00Heredity (Edinb). 2008 Feb;100(2):158-70. Epub 2007 Feb 21.

}, month = {Feb}, pages = {158-70}, abstract = {

A central challenge in evolutionary biology is to identify genes underlying ecologically important traits and describe the fitness consequences of naturally occurring variation at these loci. To address this goal, several novel approaches have been developed, including {\textquoteright}population genomics,{\textquoteright} where a large number of molecular markers are scored in individuals from different environments with the goal of identifying markers showing unusual patterns of variation, potentially due to selection at linked sites. Such approaches are appealing because of (1) the increasing ease of generating large numbers of genetic markers, (2) the ability to scan the genome without measuring phenotypes and (3) the simplicity of sampling individuals without knowledge of their breeding history. Although such approaches are inherently applicable to non-model systems, to date these studies have been limited in their ability to uncover functionally relevant genes. By contrast, quantitative genetics has a rich history, and more recently, quantitative trait locus (QTL) mapping has had some success in identifying genes underlying ecologically relevant variation even in novel systems. QTL mapping, however, requires (1) genetic markers that specifically differentiate parental forms, (2) a focus on a particular measurable phenotype and (3) controlled breeding and maintenance of large numbers of progeny. Here we present current advances and suggest future directions that take advantage of population genomics and quantitative genetic approaches - in both model and non-model systems. Specifically, we discuss advantages and limitations of each method and argue that a combination of the two provides a powerful approach to uncovering the molecular mechanisms responsible for adaptation.

}, keywords = {*Genetics, Population, *Genomics, Animals, Ecosystem, Genetic Markers, Humans, Plants/genetics, Quantitative Trait Loci}, isbn = {1365-2540 (Electronic)0018-067X (Linking)}, author = {Stinchcombe, J. R. and Hoekstra, HE} } @article {549436, title = {Comparative analysis of testis protein evolution in rodents}, journal = {Genetics}, volume = {179}, number = {4}, year = {2008}, note = {

Turner, Leslie MChuong, Edward BHoekstra, Hopi EengT32 HG000044/HG/NHGRI NIH HHS/Howard Hughes Medical Institute/Comparative StudyResearch Support, Non-U.S. Gov{\textquoteright}tResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.2008/08/12 09:00Genetics. 2008 Aug;179(4):2075-89. doi: 10.1534/genetics.107.085902. Epub 2008 Aug 9.

}, month = {Aug}, pages = {2075-89}, abstract = {

Genes expressed in testes are critical to male reproductive success, affecting spermatogenesis, sperm competition, and sperm-egg interaction. Comparing the evolution of testis proteins at different taxonomic levels can reveal which genes and functional classes are targets of natural and sexual selection and whether the same genes are targets among taxa. Here we examine the evolution of testis-expressed proteins at different levels of divergence among three rodents, mouse (Mus musculus), rat (Rattus norvegicus), and deer mouse (Peromyscus maniculatus), to identify rapidly evolving genes. Comparison of expressed sequence tags (ESTs) from testes suggests that proteins with testis-specific expression evolve more rapidly on average than proteins with maximal expression in other tissues. Genes with the highest rates of evolution have a variety of functional roles including signal transduction, DNA binding, and egg-sperm interaction. Most of these rapidly evolving genes have not been identified previously as targets of selection in comparisons among more divergent mammals. To determine if these genes are evolving rapidly among closely related species, we sequenced 11 of these genes in six Peromyscus species and found evidence for positive selection in five of them. Together, these results demonstrate rapid evolution of functionally diverse testis-expressed proteins in rodents, including the identification of amino acids under lineage-specific selection in Peromyscus. Evidence for positive selection among closely related species suggests that changes in these proteins may have consequences for reproductive isolation.

}, keywords = {*Evolution, Molecular, Amino Acid Sequence, Animals, Expressed Sequence Tags, genome, Male, Mice, Molecular Sequence Data, Peromyscus/genetics, Proteins/*genetics, Rats, Rodentia/*genetics, Selection, Genetic, Sequence Alignment, Spermatogenesis/*genetics, Testis/*metabolism}, isbn = {0016-6731 (Print)0016-6731 (Linking)}, author = {Turner, L. M. and Chuong, E. B. and Hoekstra, HE} } @article {549381, title = {Natural selection along an environmental gradient: A classic cline in mouse pigmentation}, journal = {Evolution}, volume = {62}, number = {7}, year = {2008}, note = {

Mullen, Lynne MHoekstra, Hopi EengResearch Support, Non-U.S. Gov{\textquoteright}tResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.2008/05/21 09:00Evolution. 2008 Jul;62(7):1555-70. doi: 10.1111/j.1558-5646.2008.00425.x.

}, month = {Jul}, pages = {1555-70}, abstract = {

We revisited a classic study of morphological variation in the oldfield mouse (Peromyscus polionotus) to estimate the strength of selection acting on pigmentation patterns and to identify the underlying genes. We measured 215 specimens collected by Francis Sumner in the 1920s from eight populations across a 155-km, environmentally variable transect from the white sands of Florida{\textquoteright}s Gulf coast to the dark, loamy soil of southeastern Alabama. Like Sumner, we found significant variation among populations: mice inhabiting coastal sand dunes had larger feet, longer tails, and lighter pigmentation than inland populations. Most striking, all seven pigmentation traits examined showed a sharp decrease in reflectance about 55 km from the coast, with most of the phenotypic change occurring over less than 10 km. The largest change in soil reflectance occurred just south of this break in pigmentation. Geographic analysis of microsatellite markers shows little interpopulation differentiation, so the abrupt change in pigmentation is not associated with recent secondary contact or reduced gene flow between adjacent populations. Using these genetic data, we estimated that the strength of selection needed to maintain the observed distribution of pigment traits ranged from 0.0004 to 21\%, depending on the trait and model used. We also examined changes in allele frequency of SNPs in two pigmentation genes, Mc1r and Agouti, and show that mutations in the cis-regulatory region of Agouti may contribute to this cline in pigmentation. The concordance between environmental variation and pigmentation in the face of high levels of interpopulation gene flow strongly implies that natural selection is maintaining a steep cline in pigmentation and the genes underlying it.

}, keywords = {*Ecosystem, *Selection, Genetic, Agouti Signaling Protein/genetics, Alabama, Animals, Florida, Gene Flow, Gene Frequency, Genetic Variation, Geography, Linkage Disequilibrium, Mutation, Peromyscus/anatomy \& histology/*genetics, Phenotype, Pigmentation/*genetics, Polymorphism, Single Nucleotide, Receptor, Melanocortin, Type 1/genetics}, isbn = {0014-3820 (Print)0014-3820 (Linking)}, author = {Mullen, L. M. and Hoekstra, HE} } @article {549451, title = {Reproductive protein evolution within and between species: Maintenance of divergent ZP3 alleles in Peromyscus}, journal = {Molecular Ecology}, volume = {17}, number = {11}, year = {2008}, month = {Jun}, pages = {2616-28}, abstract = {

In a variety of animal taxa, proteins involved in reproduction evolve more rapidly than nonreproductive proteins. Most studies of reproductive protein evolution, however, focus on divergence between species, and little is known about differentiation among populations within a species. Here we investigate the molecular population genetics of the protein ZP3 within two Peromyscus species. ZP3 is an egg coat protein involved in primary binding of egg and sperm and is essential for fertilization. We find that amino acid polymorphism in the sperm-combining region of ZP3 is high relative to silent polymorphism in both species of Peromyscus. In addition, while there is geographical structure at a mitochondrial gene (Cytb), a nuclear gene (Lcat) and eight microsatellite loci, we find no evidence for geographical structure at Zp3 in Peromyscus truei. These patterns are consistent with the maintenance of ZP3 alleles by balancing selection, possibly due to sexual conflict or pathogen resistance. However, we do not find evidence that reinforcement promotes ZP3 diversification; allelic variation in P. truei is similar among populations, including populations allopatric and sympatric with sibling species. In fact, most alleles are present in all populations sampled across P. truei{\textquoteright}s range. While additional data are needed to identify the precise evolutionary forces responsible for sequence variation in ZP3, our results suggest that in Peromyscus, selection to maintain divergent alleles within species contributes to the pattern of rapid amino acid substitution observed among species.

}, keywords = {Alleles, Animals, DNA, Mitochondrial/genetics, Egg Proteins/*genetics, Evolution, Molecular, Genetic Variation, Genotype, Membrane Glycoproteins/*genetics, mexico, Microsatellite Repeats/genetics, Molecular Sequence Data, Peromyscus/*genetics, Receptors, Cell Surface/*genetics, Reproduction/*genetics, Sequence Analysis, DNA, United States}, isbn = {1365-294X (Electronic)0962-1083 (Linking)}, author = {Turner, L. M. and Hoekstra, HE} } @article {549306, title = {Rodents}, journal = {Current Biology}, volume = {18}, number = {10}, year = {2008}, month = {May 20}, pages = {R406-10}, keywords = {Animals, Biodiversity, Biological Evolution, Female, Humans, Male, Rodentia/*classification/*physiology, Terminology as Topic}, isbn = {0960-9822 (Print)0960-9822 (Linking)}, author = {Kay, E. H. and Hoekstra, HE} } @article {549426, title = {Adaptive variation in beach mice produced by two interacting pigmentation genes}, journal = {PLoS Biology}, volume = {5}, number = {9}, year = {2007}, note = {

Steiner, Cynthia CWeber, Jesse NHoekstra, Hopi EengP40-RR14279/RR/NCRR NIH HHS/Research Support, N.I.H., ExtramuralResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.2007/08/19 09:00PLoS Biol. 2007 Sep;5(9):e219.

}, month = {Sep}, pages = {e219}, abstract = {

Little is known about the genetic basis of ecologically important morphological variation such as the diverse color patterns of mammals. Here we identify genetic changes contributing to an adaptive difference in color pattern between two subspecies of oldfield mice (Peromyscus polionotus). One mainland subspecies has a cryptic dark brown dorsal coat, while a younger beach-dwelling subspecies has a lighter coat produced by natural selection for camouflage on pale coastal sand dunes. Using genome-wide linkage mapping, we identified three chromosomal regions (two of major and one of minor effect) associated with differences in pigmentation traits. Two candidate genes, the melanocortin-1 receptor (Mc1r) and its antagonist, the Agouti signaling protein (Agouti), map to independent regions that together are responsible for most of the difference in pigmentation between subspecies. A derived mutation in the coding region of Mc1r, rather than change in its expression level, contributes to light pigmentation. Conversely, beach mice have a derived increase in Agouti mRNA expression but no changes in protein sequence. These two genes also interact epistatically: the phenotypic effects of Mc1r are visible only in genetic backgrounds containing the derived Agouti allele. These results demonstrate that cryptic coloration can be based largely on a few interacting genes of major effect.

}, keywords = {*Epistasis, Genetic, Adaptation, Physiological/*genetics, Animals, Color, Genetic Linkage, Genetic Variation, Genomics, Mice, Mutation, Peromyscus/*genetics, Pigmentation/*genetics, Receptor, Melanocortin, Type 1/*genetics, Species Specificity}, isbn = {1545-7885 (Electronic)1544-9173 (Linking)}, author = {Steiner, C. C. and Weber, J. N. and Hoekstra, HE} } @article {549216, title = {Evolution of protein expression: New genes for a new diet}, journal = {Current Biology}, volume = {17}, number = {23}, year = {2007}, note = {

Coyne, Jerry AHoekstra, Hopi EengEngland2007/12/07 09:00Curr Biol. 2007 Dec 4;17(23):R1014-6.

}, month = {Dec 4}, pages = {R1014-6}, abstract = {

A new study identifies gene duplication of a salivary enzyme as a recent adaptation to changes in diet among human populations, highlighting the diverse ways that gene regulation can evolve.

}, keywords = {*Diet, *Evolution, Molecular, *Gene Duplication, *Gene Expression Regulation, Amylases/*genetics/metabolism, Animals, Gene Dosage/genetics, Genetic Variation/genetics, Humans, Saliva/*enzymology, Starch/pharmacology}, isbn = {0960-9822 (Print)0960-9822 (Linking)}, author = {Coyne, J. A. and Hoekstra, HE} } @article {549251, title = {The locus of evolution: Evo devo and the genetics of adaptation}, journal = {Evolution}, volume = {61}, number = {5}, year = {2007}, note = {

Hoekstra, Hopi ECoyne, Jerry AengGM058260/GM/NIGMS NIH HHS/Research Support, N.I.H., ExtramuralResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.Review2007/05/12 09:00Evolution. 2007 May;61(5):995-1016.

}, month = {May}, pages = {995-1016}, abstract = {

An important tenet of evolutionary developmental biology ("evo devo") is that adaptive mutations affecting morphology are more likely to occur in the cis-regulatory regions than in the protein-coding regions of genes. This argument rests on two claims: (1) the modular nature of cis-regulatory elements largely frees them from deleterious pleiotropic effects, and (2) a growing body of empirical evidence appears to support the predominant role of gene regulatory change in adaptation, especially morphological adaptation. Here we discuss and critique these assertions. We first show that there is no theoretical or empirical basis for the evo devo contention that adaptations involving morphology evolve by genetic mechanisms different from those involving physiology and other traits. In addition, some forms of protein evolution can avoid the negative consequences of pleiotropy, most notably via gene duplication. In light of evo devo claims, we then examine the substantial data on the genetic basis of adaptation from both genome-wide surveys and single-locus studies. Genomic studies lend little support to the cis-regulatory theory: many of these have detected adaptation in protein-coding regions, including transcription factors, whereas few have examined regulatory regions. Turning to single-locus studies, we note that the most widely cited examples of adaptive cis-regulatory mutations focus on trait loss rather than gain, and none have yet pinpointed an evolved regulatory site. In contrast, there are many studies that have both identified structural mutations and functionally verified their contribution to adaptation and speciation. Neither the theoretical arguments nor the data from nature, then, support the claim for a predominance of cis-regulatory mutations in evolution. Although this claim may be true, it is at best premature. Adaptation and speciation probably proceed through a combination of cis-regulatory and structural mutations, with a substantial contribution of the latter.

}, keywords = {*Biological Evolution, *Regulatory Elements, Transcriptional, Animals, Genes, Genomics, Morphogenesis/*genetics, Mutation}, isbn = {0014-3820 (Print)0014-3820 (Linking)}, author = {Hoekstra, HE and Coyne, J. A.} } @article {782466, title = {Sixty polymorphic microsatellite markers for the oldfield mouse developed in Peromyscus polionotus and Peromyscus maniculatus}, journal = {Molecular Ecology}, volume = {6}, year = {2006}, pages = {36-40}, abstract = {

We isolated and characterized 60 novel microsatellite markers from the closely related oldfield mouse (Peromyscus polionotus) and deer mouse (Peromyscus maniculatus) for studies of conservation, ecological, quantitative and population genetics. We assessed all 60 markers in a wild population of\ Peromyscus polionotus rhoadsi\ (N\ =\ 20) from central Florida and found an average of nine alleles per marker and an observed heterozygosity (HO) of 0.66 (range\ =\ 0.00{\textendash}1.00). These polymorphic markers contribute to the growing number of genomic resources for\ Peromyscus, an emerging model system for ecological and evolutionary research.

}, author = {Mullen, L. M. and Hirschmann, R. J. and K.L. Prince and Glenn, T. C. and Dewey, M. J. and Hoekstra, H. E.} } @article {549441, title = {Adaptive evolution of fertilization proteins within a genus: Variation in ZP2 and ZP3 in deer mice (Peromyscus)}, journal = {Molecular Biology and Evolution}, volume = {23}, number = {9}, year = {2006}, note = {

Turner, Leslie MHoekstra, Hopi EengResearch Support, Non-U.S. Gov{\textquoteright}tResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.2006/06/16 09:00Mol Biol Evol. 2006 Sep;23(9):1656-69. Epub 2006 Jun 14.

}, month = {Sep}, pages = {1656-69}, abstract = {

Rapid evolution of reproductive proteins has been documented in a wide variety of taxa. In internally fertilized species, knowledge about the evolutionary dynamics of these proteins between closely related taxa is primarily limited to accessory gland proteins in the semen of Drosophila. Investigation of additional taxa and functional classes of proteins is necessary in order to determine if there is a general pattern of adaptive evolution of reproductive proteins between recently diverged species. We performed an evolutionary analysis of 2 egg coat proteins, ZP2 and ZP3, in 15 species of deer mice (genus Peromyscus). Both of these proteins are involved in egg-sperm binding, a critical step in maintaining species-specific fertilization. Here, we show that Zp2 and Zp3 gene trees are not consistent with trees based on nonreproductive genes, Mc1r and Lcat, where species formed monophyletic clades. In fact, for both of the reproductive genes, intraspecific amino acid variation was extensive and alleles were sometimes shared across species. We document positive selection acting on ZP2 and ZP3 and identify specific amino acid sites that are likely targets of selection using both maximum likelihood approaches and patterns of parallel amino acid change. In ZP3, positively selected sites are clustered in and around the region implicated in sperm binding in Mus, suggesting changes may impact egg-sperm binding and fertilization potential. Finally, we identify lineages with significantly elevated rates of amino acid substitution using a Bayesian mapping approach. These findings demonstrate that the pattern of adaptive reproductive protein evolution found at higher taxonomic levels can be documented between closely related mammalian species, where reproductive isolation has evolved recently.

}, keywords = {*Adaptation, Biological, *Evolution, Molecular, *Genetic Variation, Amino Acid Sequence, Amino Acid Substitution, Animals, Egg Proteins/chemistry/*genetics, Fertilization/*genetics, Membrane Glycoproteins/*genetics, Molecular Sequence Data, Peptide Mapping, Peromyscus/*genetics, Phylogeny, Receptors, Cell Surface/*genetics, Sequence Homology, Amino Acid}, isbn = {0737-4038 (Print)0737-4038 (Linking)}, author = {Turner, L. M. and Hoekstra, H. E.} } @article {549241, title = {Genetics, development and evolution of adaptive pigmentation in vertebrates}, journal = {Heredity}, volume = {97}, number = {3}, year = {2006}, note = {

Hoekstra, H EengResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.ReviewEngland2006/07/11 09:00Heredity (Edinb). 2006 Sep;97(3):222-34. Epub 2006 Jul 5.

}, month = {Sep}, pages = {222-34}, abstract = {

The study of pigmentation has played an important role in the intersection of evolution, genetics, and developmental biology. Pigmentation{\textquoteright}s utility as a visible phenotypic marker has resulted in over 100 years of intense study of coat color mutations in laboratory mice, thereby creating an impressive list of candidate genes and an understanding of the developmental mechanisms responsible for the phenotypic effects. Variation in color and pigment patterning has also served as the focus of many classic studies of naturally occurring phenotypic variation in a wide variety of vertebrates, providing some of the most compelling cases for parallel and convergent evolution. Thus, the pigmentation model system holds much promise for understanding the nature of adaptation by linking genetic changes to variation in fitness-related traits. Here, I first discuss the historical role of pigmentation in genetics, development and evolutionary biology. I then discuss recent empirically based studies in vertebrates, which rely on these historical foundations to make connections between genotype and phenotype for ecologically important pigmentation traits. These studies provide insight into the evolutionary process by uncovering the genetic basis of adaptive traits and addressing such long-standing questions in evolutionary biology as (1) are adaptive changes predominantly caused by mutations in regulatory regions or coding regions? (2) is adaptation driven by the fixation of dominant mutations? and (3) to what extent are parallel phenotypic changes caused by similar genetic changes? It is clear that coloration has much to teach us about the molecular basis of organismal diversity, adaptation and the evolutionary process.

}, keywords = {*Adaptation, Biological/genetics, *Biological Evolution, *Evolution, Molecular, *Gene Expression Regulation, Developmental, *Pigmentation/genetics/physiology, Animals, Genetic Variation, Mice, Vertebrates/genetics/*growth \& development}, isbn = {0018-067X (Print)0018-067X (Linking)}, author = {Hoekstra, H. E.} } @article {549266, title = {A single amino acid mutation contributes to adaptive beach mouse color pattern}, journal = {Science}, volume = {313}, number = {5783}, year = {2006}, note = {

Hoekstra, Hopi EHirschmann, Rachel JBundey, Richard AInsel, Paul ACrossland, Janet PengP40-RR14279/RR/NCRR NIH HHS/Research Support, N.I.H., ExtramuralResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.New York, N.Y.2006/07/11 09:00Science. 2006 Jul 7;313(5783):101-4.

}, month = {Jul 7}, pages = {101-4}, abstract = {

Natural populations of beach mice exhibit a characteristic color pattern, relative to their mainland conspecifics, driven by natural selection for crypsis. We identified a derived, charge-changing amino acid mutation in the melanocortin-1 receptor (Mc1r) in beach mice, which decreases receptor function. In genetic crosses, allelic variation at Mc1r explains 9.8\% to 36.4\% of the variation in seven pigmentation traits determining color pattern. The derived Mc1r allele is present in Florida{\textquoteright}s Gulf Coast beach mice but not in Atlantic coast mice with similar light coloration, suggesting that different molecular mechanisms are responsible for convergent phenotypic evolution. Here, we link a single mutation in the coding region of a pigmentation gene to adaptive quantitative variation in the wild.

}, keywords = {*Mutation, Adaptation, Biological, Alleles, Amino Acid Substitution, Animals, Cell Line, Crosses, Genetic, Cyclic AMP/metabolism, Female, Florida, Gene Frequency, Genotype, Hair, Hair Color/*genetics, Humans, Male, Molecular Sequence Data, Peromyscus/*genetics, Phenotype, Pigmentation/*genetics, Polymorphism, Single Nucleotide, Principal Component Analysis, Receptor, Melanocortin, Type 1/chemistry/*genetics/metabolism, Sequence Analysis, DNA}, isbn = {1095-9203 (Electronic)0036-8075 (Linking)}, author = {Hoekstra, HE and Hirschmann, R. J. and Bundey, R. A. and Insel, P. A. and Crossland, J. P.} } @article {549511, title = {Coat-color variation in rock pocket mice (Chaetopidus intermedius): from phenotype to genotype.}, journal = {Zoology}, volume = {133}, year = {2005}, pages = {79-99}, abstract = {

In a series of classic studies in mammalian evolutionary biology, Sumner (1921), Benson (1933), and Dice and Blossom (1937) described striking coat color variation in the rock pocket mouse, Chaetodipus intermedius, in the deserts of Arizona and New Mexico. These authors showed that C. intermedius coat color typically matches the color of the rocks on which the mice live; the dorsal pelage varies from a light, sandy color for populations found on some granites to a dark, nearly black color for populations found on basalt lava flows. Dice and Blossom (1937) suggested that this crypsis is an adaptation to avoid predation. Motivated by the wealth of data on the genetics, biochemistry, and molecular biology of the pigmentation process, we have used a candidate-gene approach to identify the genetic basis of adaptive coat color variation in C. intermedius. We review our recent studies on this topic with emphasis on the following key results: the identification of a single gene (the melanocortin-1-receptor, Mc1r) in one population that appears to be largely responsible for color differences, the balance between selection and migration among neighboring melanic and light races, and the finding that melanism has evolved independently on different lava flows through changes at different genes.\ 

}, author = {Hoekstra, HE and Nachman, M. W.} } @article {549281, title = {Local adaptation in the rock pocket mouse (Chaetodipus intermedius): Natural selection and phylogenetic history of populations}, journal = {Heredity}, volume = {94}, number = {2}, year = {2005}, note = {

Hoekstra, H EKrenz, J GNachman, M WengComparative StudyResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.Research Support, U.S. Gov{\textquoteright}t, P.H.S.England2004/11/04 09:00Heredity (Edinb). 2005 Feb;94(2):217-28.

}, month = {Feb}, pages = {217-28}, abstract = {

Elucidating the causes of population divergence is a central goal of evolutionary biology. Rock pocket mice, Chaeotdipus intermedius, are an ideal system in which to study intraspecific phenotypic divergence because of the extensive color variation observed within this species. Here, we investigate whether phenotypic variation in color is correlated with local environmental conditions or with phylogenetic history. First, we quantified variation in pelage color (n=107 mice) and habitat color (n=51 rocks) using a spectrophotometer, and showed that there was a correlation between pelage color and habitat color across 14 sampled populations (R2=0.43). Analyses of mtDNA sequences from these same individuals revealed strong population structure in this species across its range, where most variation (63\%) was partitioned between five geographic regions. Using Mantel tests, we show that there is no correlation between color variation and mtDNA phylogeny, suggesting that pelage coloration has evolved rapidly. At a finer geographical scale, high levels of gene flow between neighboring melanic and light populations suggest the selection acting on color must be quite strong to maintain habitat-specific phenotypic distributions. Finally, we raise the possibility that, in some cases, migration between populations of pocket mice inhabiting different lava flows may be responsible for similar melanic phenotypes in different populations. Together, the results suggest that color variation can evolve very rapidly over small geographic scales and that gene flow can both hinder and promote local adaptation.

}, keywords = {*Environment, *Phenotype, *Phylogeny, *Selection, Genetic, Adaptation, Physiological/*physiology, Animals, Arizona, Base Sequence, DNA, Mitochondrial/genetics, Genetics, Population, Geography, Molecular Sequence Data, New Mexico, Pigmentation/*physiology, Population dynamics, Rodentia/*genetics/physiology, Sequence Alignment, Sequence Analysis, DNA, Spectrophotometry}, isbn = {0018-067X (Print)0018-067X (Linking)}, author = {Hoekstra, HE and Krenz, J. G. and Nachman, M. W.} } @article {549411, title = {Adaptive reptile color variation and the evolution of the Mc1r gene}, journal = {Evolution}, volume = {58}, number = {8}, year = {2004}, note = {

Rosenblum, Erica BreeHoekstra, Hopi ENachman, Michael WengComparative StudyResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.Research Support, U.S. Gov{\textquoteright}t, P.H.S.2004/09/28 05:00Evolution. 2004 Aug;58(8):1794-808.

}, month = {Aug}, pages = {1794-808}, abstract = {

The wealth of information on the genetics of pigmentation and the clear fitness consequences of many pigmentation phenotypes provide an opportunity to study the molecular basis of an ecologically important trait. The melanocortin-1 receptor (Mc1r) is responsible for intraspecific color variation in mammals and birds. Here, we study the molecular evolution of Mc1r and investigate its role in adaptive intraspecific color differences in reptiles. We sequenced the complete Mc1r locus in seven phylogenetically diverse squamate species with melanic or blanched forms associated with different colored substrates or thermal environments. We found that patterns of amino acid substitution across different regions of the receptor are similar to the patterns seen in mammals, suggesting comparable levels of constraint and probably a conserved function for Mc1r in mammals and reptiles. We also found high levels of silent-site heterozygosity in all species, consistent with a high mutation rate or large long-term effective population size. Mc1r polymorphisms were strongly associated with color differences in Holbrookia maculata and Aspidoscelis inornata. In A. inornata, several observations suggest that Mc1r mutations may contribute to differences in color: (1) a strong association is observed between one Mc1r amino acid substitution and dorsal color; (2) no significant population structure was detected among individuals from these populations at the mitochondrial ND4 gene; (3) the distribution of allele frequencies at Mc1r deviates from neutral expectations; and (4) patterns of linkage disequilibrium at Mc1r are consistent with recent selection. This study provides comparative data on a nuclear gene in reptiles and highlights the utility of a candidate-gene approach for understanding the evolution of genes involved in vertebrate adaptation.

}, keywords = {*Adaptation, Physiological, *Evolution, Molecular, Amino Acid Sequence, Animals, Base Sequence, california, Conserved Sequence, DNA Primers, Gene Frequency, Linkage Disequilibrium, Lizards/*genetics/physiology, Molecular Sequence Data, Mutation/genetics, New Mexico, Pigmentation/*genetics/physiology, Polymorphism, Genetic, Receptor, Melanocortin, Type 1/*genetics, Selection, Genetic, Sequence Alignment, Sequence Analysis, DNA, Snakes/*genetics/physiology}, isbn = {0014-3820 (Print)0014-3820 (Linking)}, author = {Rosenblum, E. B. and Hoekstra, HE and Nachman, M. W.} } @article {549256, title = {Ecological genetics of adaptive color polymorphism in pocket mice: geographic variation in selected and neutral genes}, journal = {Evolution}, volume = {58}, number = {6}, year = {2004}, note = {

Hoekstra, Hopi EDrumm, Kristen ENachman, Michael WengComparative StudyResearch Support, Non-U.S. Gov{\textquoteright}tResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.Research Support, U.S. Gov{\textquoteright}t, P.H.S.2004/07/23 05:00Evolution. 2004 Jun;58(6):1329-41.

}, month = {Jun}, pages = {1329-41}, abstract = {

Patterns of geographic variation in phenotype or genotype may provide evidence for natural selection. Here, we compare phenotypic variation in color, allele frequencies of a pigmentation gene (the melanocortin-1 receptor, Mc1r), and patterns of neutral mitochondrial DNA (mtDNA) variation in rock pocket mice (Chaetodipus intermedius) across a habitat gradient in southern Arizona. Pocket mice inhabiting volcanic lava have dark coats with unbanded, uniformly melanic hairs, whereas mice from nearby light-colored granitic rocks have light coats with banded hairs. This color polymorphism is a presumed adaptation to avoid predation. Previous work has demonstrated that two Mc1r alleles, D and d, differ by four amino acids, and are responsible for the color polymorphism: DD and Dd genotypes are melanic whereas dd genotypes are light colored. To determine the frequency of the two Mc1r allelic classes across the dark-colored lava and neighboring light-colored granite, we sequenced the Mc1r gene in 175 individuals from a 35-km transect in the Pinacate lava region. We also sequenced two neutral mtDNA genes, COIII and ND3, in the same individuals. We found a strong correlation between Mc1r allele frequency and habitat color and no correlation between mtDNA markers and habitat color. Using estimates of migration from mtDNA haplotypes between dark- and light-colored sampling sites and Mc1r allele frequencies at each site, we estimated selection coefficients against mismatched Mc1r alleles, assuming a simple model of migration-selection balance. Habitat-dependent selection appears strong but asymmetric: selection is stronger against light mice on dark rock than against melanic mice on light rock. Together these results suggest that natural selection acts to match pocket mouse coat color to substrate color, despite high levels of gene flow between light and melanic populations.

}, keywords = {*Environment, *Genetic Variation, *Phenotype, *Phylogeny, *Selection, Genetic, Animals, Arizona, Base Sequence, Cluster Analysis, DNA Primers, DNA, Mitochondrial/genetics, Gene Frequency, Genetics, Population, Geography, Likelihood Functions, Models, Genetic, Molecular Sequence Data, Pigmentation/*genetics/physiology, Receptor, Melanocortin, Type 1/genetics, Rodentia/*genetics/physiology, Sequence Analysis, DNA, Spectrophotometry}, isbn = {0014-3820 (Print)0014-3820 (Linking)}, author = {Hoekstra, HE and Drumm, K. E. and Nachman, M. W.} } @article {549291, title = {Parallel evolution is in the genes}, journal = {Science}, volume = {303}, number = {5665}, year = {2004}, note = {

Hoekstra, Hopi EPrice, TrevorengCommentNew York, N.Y.2004/03/20 05:00Science. 2004 Mar 19;303(5665):1779-81.

}, month = {Mar 19}, pages = {1779-81}, keywords = {*Biological Evolution, *Feathers, *Polymorphism, Genetic, Amino Acid Substitution, Animals, Arctic Regions, Birds/anatomy \& histology/*genetics/physiology, Color, Female, Geese/anatomy \& histology/genetics/physiology, Gene Frequency, Heterozygote, Male, Melanins/analysis/biosynthesis, Mutation, Phenotype, Phylogeny, Pigmentation/*genetics, Receptor, Melanocortin, Type 1/chemistry/*genetics, Selection, Genetic, Sexual Behavior, Animal}, isbn = {1095-9203 (Electronic)0036-8075 (Linking)}, author = {Hoekstra, HE and Price, T.} } @article {782506, title = {Unequal transmission of mitochondrial haplotypes in natural populations of field mice with XY females (genus Akodon)}, journal = {The American Naturalist}, volume = {161}, year = {2003}, pages = {29-39}, abstract = {

In species with fertile XY females, such as South American\ field mice (genus Akodon), there are two types of mitochondrial\ DNA (mtDNA), one passing from XX females and one from XY\ females. The XX mothers pass their mtDNA to their XX daughters.\ The XY mothers, however, produce both XX and XY daughters.\ Because of this breeding scheme, the XY mtDNA remains isolated\ whereas the XX lineage is continuously invaded by XY mtDNA haplotypes.\ Using a set of recursion equations, I predicted that XY\ mtDNA haplotypes should rapidly spread through entire populations\ composed of both XX and XY females. I examined patterns of nucleotide\ polymorphism and divergence from the mtDNA control\ region as well as phylogenetic patterns for evidence of an mtDNA\ sweep. I compared patterns in two sister species, Akodon boliviensis\ and Akodon azarae, that are composed of 35\% and 10\% XY females,\ respectively. Akodon boliviensis XY females are found in all clades of\ a phylogenetic mtDNA tree consistent with the spread of mtDNA\ haplotypes. In addition, A. azarae mtDNA haplotypes showed no\ deviations from neutrality. These results, in combination with high\ levels of mtDNA nucleotide diversity in XY females, suggest an ancient\ origin (1104 generations) of XY females in both A. boliviensis\ and A. azarae.

}, author = {Hoekstra, HE} } @article {549286, title = {Different genes underlie adaptive melanism in different populations of rock pocket mice}, journal = {Mol Ecol}, volume = {12}, number = {5}, year = {2003}, note = {

Hoekstra, H ENachman, M WengComparative StudyResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.Research Support, U.S. Gov{\textquoteright}t, P.H.S.England2003/04/16 05:00Mol Ecol. 2003 May;12(5):1185-94.

}, month = {May}, pages = {1185-94}, abstract = {

Identifying the genes responsible for adaptation has been an elusive goal in evolutionary biology. Rock pocket mice (Chaetodipus intermedius) provide a useful system for studying the genetics of adaptation: most C. intermedius are light-coloured and live on light-coloured rocks, but in several different geographical regions, C. intermedius are melanic and live on dark-coloured basalt lava, presumably as an adaptation for crypsis. Previous work demonstrated that mutations at the melanocortin-1 receptor gene (Mc1r) are responsible for the dark/light difference in mice from one population in Arizona. Here, we investigate whether melanism has evolved independently in populations of dark C. intermedius from New Mexico, and whether the same or different genes underlie the dark phenotype in mice from these populations compared with the dark mice from Arizona. Seventy-six mice were collected from pairs of dark and light localities representing four different lava flows and adjacent light-coloured rocks; lava flows were separated by 70-750 km. Spectrophotometric analysis of mouse pelage and of rock samples revealed a strong positive association between coat colour and substrate colour. No significant differences were observed in the colour of rocks among the four lava flows, suggesting that mice in these separate populations have experienced similar selection for crypsis. Despite this similarity in environment, melanic mice from the three New Mexico populations were slightly, but significantly, darker than melanic mice from Arizona. The entire Mc1r gene was sequenced in all mice. The previously identified mutations responsible for the light/dark difference in mice from Arizona were absent in all melanic mice from three different populations in New Mexico. Five new Mc1r polymorphisms were observed among mice from New Mexico, but none showed any association with coat colour. These results indicate that adaptive melanism has arisen at least twice in C. intermedius and that these similar phenotypic changes have a different genetic basis.

}, keywords = {*Environment, Adaptation, Biological/*genetics/physiology, Animals, Arizona, Base Sequence, DNA Primers, Hair/physiology, Melanosis/*genetics, New Mexico, Polymorphism, Genetic, Rodentia/*genetics, Sequence Analysis, DNA, Spectrophotometry}, isbn = {0962-1083 (Print)0962-1083 (Linking)}, author = {Hoekstra, HE and Nachman, M. W.} } @article {549391, title = {The genetic basis of adaptive melanism in pocket mice}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {100}, number = {9}, year = {2003}, note = {

Nachman, Michael WHoekstra, Hopi ED{\textquoteright}Agostino, Susan LengResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.Research Support, U.S. Gov{\textquoteright}t, P.H.S.2003/04/22 05:00Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5268-73. Epub 2003 Apr 18.

}, month = {Apr 29}, pages = {5268-73}, abstract = {

Identifying the genes underlying adaptation is a major challenge in evolutionary biology. Here, we describe the molecular changes underlying adaptive coat color variation in a natural population of rock pocket mice, Chaetodipus intermedius. Rock pocket mice are generally light-colored and live on light-colored rocks. However, populations of dark (melanic) mice are found on dark lava, and this concealing coloration provides protection from avian and mammalian predators. We conducted association studies by using markers in candidate pigmentation genes and discovered four mutations in the melanocortin-1-receptor gene, Mc1r, that seem to be responsible for adaptive melanism in one population of lava-dwelling pocket mice. Interestingly, another melanic population of these mice on a different lava flow shows no association with Mc1r mutations, indicating that adaptive dark color has evolved independently in this species through changes at different genes.

}, keywords = {Adaptation, Physiological/*genetics, Amino Acid Sequence, Animals, Base Sequence, DNA Primers, Melanosis/*genetics/physiopathology, Mice, Molecular Sequence Data, Polymorphism, Genetic, Receptors, Corticotropin/genetics, Receptors, Melanocortin, Sequence Homology, Amino Acid, Sequence Homology, Nucleic Acid}, isbn = {0027-8424 (Print)0027-8424 (Linking)}, author = {Nachman, M. W. and Hoekstra, H. E. and D{\textquoteright}Agostino, S. L.} } @article {549341, title = {Expression and conservation of processed copies of the RBMX gene}, journal = {Mammalian Genome}, volume = {12}, number = {7}, year = {2001}, note = {

Lingenfelter, P ADelbridge, M LThomas, SHoekstra, H EMitchell, M JGraves, J ADisteche, C MengGM 46883/GM/NIGMS NIH HHS/Research Support, Non-U.S. Gov{\textquoteright}tResearch Support, U.S. Gov{\textquoteright}t, P.H.S.2001/06/23 10:00Mamm Genome. 2001 Jul;12(7):538-45.

}, month = {Jul}, pages = {538-45}, abstract = {

RBMX and RBMY are members of an ancient pair of genes located on the sex chromosomes that encode RNA-binding proteins involved in splicing. These genes have differentiated and evolved separately on the X and Y Chromosomes. RBMY has acquired a testis-specific function, whereas, as shown here, RBMX is ubiquitously expressed and is subject to X inactivation. We have also found that multiple processed copies of RBMX are present in the human genome. RBMX-like sequences (RBMXLs) located on human Chrs 1, 4, 6, 9 (9p13 and 9p24), 11, 20, and X lack introns and thus probably result from retroposition events. We found RBMXLs to be conserved in primates and great apes at corresponding chromosomal locations, indicating that they arose prior to the divergence of human. Some of the RBMXLs show insertions, deletions, and stop codons, which would probably result in nonfunctional proteins. The RBMXL on Chr 20 is deleted in some individuals. Two of the largely intact RBMXLs, located on Chrs 1 and 9p13, are expressed in different tissues and may encode novel proteins involved in splicing in a tissue-specific manner. The RBMXL located at 9p13 is specifically expressed in testis, and to a lesser extent in brain, and may therefore play a role in testis function. This autosomal, testis-specific copy of RBMX could potentially compensate for RBMX that is presumably inactivated in male germ cells, in a manner analogous to autosomal retroposed copies of other X-linked genes.

}, keywords = {*Chromosome Mapping, Amino Acid Sequence, DNA Primers/chemistry, Humans, Hybrid Cells/metabolism, In Situ Hybridization, Fluorescence, Male, Molecular Sequence Data, Nuclear Proteins, Phylogeny, Polymerase Chain Reaction, Retroelements, RNA Splicing, RNA-Binding Proteins/*genetics/metabolism, Sequence Homology, Amino Acid, Spermatogenesis, Testis/metabolism, X Chromosome/*genetics/metabolism}, isbn = {0938-8990 (Print)0938-8990 (Linking)}, author = {Lingenfelter, P. A. and Delbridge, M. L. and Thomas, S. and Hoekstra, H. E. and Mitchell, M. J. and Graves, J. A. and Disteche, C. M.} } @article {549276, title = {Strength and tempo of directional selection in the wild}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {98}, number = {16}, year = {2001}, note = {

Hoekstra, H EHoekstra, J MBerrigan, DVignieri, S NHoang, AHill, C EBeerli, PKingsolver, J GengResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.Review2001/07/27 10:00Proc Natl Acad Sci U S A. 2001 Jul 31;98(16):9157-60. Epub 2001 Jul 24.

}, month = {Jul 31}, pages = {9157-60}, abstract = {

Directional selection is a major force driving adaptation and evolutionary change. However, the distribution, strength, and tempo of phenotypic selection acting on quantitative traits in natural populations remain unclear across different study systems. We reviewed the literature (1984-1997) that reported the strength of directional selection as indexed by standardized linear selection gradients (beta). We asked how strong are viability and sexual selection, and whether strength of selection is correlated with the time scale over which it was measured. Estimates of the magnitude of directional selection (absolute value of beta) were exponentially distributed, with few estimates greater than 0.50 and most estimates less than 0.15. Sexual selection (measured by mating success) appeared stronger than viability selection (measured by survival). Viability selection that was measured over short periods (days) was typically stronger than selection measured over longer periods (months and years), but the strength of sexual selection did not vary with duration of selection episodes; as a result, sexual selection was stronger than viability selection over longer time scales (months and years), but not over short time scales (days).

}, keywords = {*Biological Evolution, *Selection, Genetic, Animals, Phenotype}, isbn = {0027-8424 (Print)0027-8424 (Linking)}, author = {Hoekstra, H. E. and Hoekstra, J. M. and Berrigan, D. and Vignieri, S. N. and Hoang, A. and Hill, C. E. and P. Beerli and Kingsolver, J. G.} } @article {549316, title = {The strength of phenotypic selection in natural populations}, journal = {The American Naturalist}, volume = {157}, number = {3}, year = {2001}, note = {

Kingsolver, J GHoekstra, H EHoekstra, J MBerrigan, DVignieri, S NHill, C EHoang, AGibert, PBeerli, Peng2008/08/19 09:00Am Nat. 2001 Mar;157(3):245-61. doi: 10.1086/319193.

}, month = {Mar}, pages = {245-61}, abstract = {

How strong is phenotypic selection on quantitative traits in the wild? We reviewed the literature from 1984 through 1997 for studies that estimated the strength of linear and quadratic selection in terms of standardized selection gradients or differentials on natural variation in quantitative traits for field populations. We tabulated 63 published studies of 62 species that reported over 2,500 estimates of linear or quadratic selection. More than 80\% of the estimates were for morphological traits; there is very little data for behavioral or physiological traits. Most published selection studies were unreplicated and had sample sizes below 135 individuals, resulting in low statistical power to detect selection of the magnitude typically reported for natural populations. The absolute values of linear selection gradients |beta| were exponentially distributed with an overall median of 0.16, suggesting that strong directional selection was uncommon. The values of |beta| for selection on morphological and on life-history/phenological traits were significantly different: on average, selection on morphology was stronger than selection on phenology/life history. Similarly, the values of |beta| for selection via aspects of survival, fecundity, and mating success were significantly different: on average, selection on mating success was stronger than on survival. Comparisons of estimated linear selection gradients and differentials suggest that indirect components of phenotypic selection were usually modest relative to direct components. The absolute values of quadratic selection gradients |gamma| were exponentially distributed with an overall median of only 0.10, suggesting that quadratic selection is typically quite weak. The distribution of gamma values was symmetric about 0, providing no evidence that stabilizing selection is stronger or more common than disruptive selection in nature.

}, isbn = {1537-5323 (Electronic)0003-0147 (Linking)}, author = {Kingsolver, J. G. and Hoekstra, H. E. and Hoekstra, J. M. and Berrigan, D. and Vignieri, S. N. and Hill, C. E. and Hoang, A. and Gibert, P. and P. Beerli} } @article {549271, title = {An unusual sex-determination system in South American field mice (genus Akodon): The role of mutation, selection, and meiotic drive in maintaining XY females}, journal = {Evolution}, volume = {55}, number = {1}, year = {2001}, note = {

Hoekstra, H EHoekstra, J MengResearch Support, Non-U.S. Gov{\textquoteright}tResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.2001/03/27 10:00Evolution. 2001 Jan;55(1):190-7.

}, month = {Jan}, pages = {190-7}, abstract = {

The mechanism of sex determination in mammals appears highly conserved: the presence of a Y chromosome triggers the male developmental pathway, whereas the absence of a Y chromosome results in a default female phenotype. However, if the Y chromosome fails to initiate the male pathway (referred to as Y*), XY* females can result, as is the case in several species of South American field mice (genus Akodon). The breeding genetics in this system inherently select against the Y* chromosome such that the frequency of XY* females should decrease rapidly to very low frequencies. However, in natural populations of Akodon, XY* females persist at substantial frequencies; for example, 10\% of females are XY* in A. azarae and 30\% in A. boliviensis. We develop a mathematical model that considers the potential roles of three evolutionary forces in maintaining XY* females: Y-to-Y* chromosome transitions (mutation), chromosome segregation distortion (meiotic drive), and differential fecundity (selection). We then test the predictions of our model using data from breeding colonies of A. azarae. We conclude that any single force is inadequate to maintain XY* females. However, a combination of segregation bias of the male and female Y chromosomes during spermatogenesis/oogenesis and increased fecundity in XY* females could account for the observed frequencies of XY* females.

}, keywords = {*Selection, Genetic, *Sex Determination Processes, Animals, Female, Fertility, Male, Meiosis, Models, Theoretical, Muridae/*genetics, Mutation, Oogenesis, Phenotype, Spermatogenesis, X Chromosome/*genetics, Y Chromosome/*genetics}, isbn = {0014-3820 (Print)0014-3820 (Linking)}, author = {Hoekstra, HE and Hoekstra, J. M.} } @article {549236, title = {MHC class II pseudogene and genomic signature of a 32-kb cosmid in the house finch (Carpodacus mexicanus)}, journal = {Genome Research}, volume = {10}, number = {5}, year = {2000}, note = {

Hess, C MGasper, JHoekstra, H EHill, C EEdwards, S VengResearch Support, Non-U.S. Gov{\textquoteright}tResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.2000/05/16 09:00Genome Res. 2000 May;10(5):613-23.

}, month = {May}, pages = {613-23}, abstract = {

Large-scale sequencing studies in vertebrates have thus far focused primarily on the genomes of a few model organisms. Birds are of interest to genomics because of their much smaller and highly streamlined genomes compared to mammals. However, large-scale genetic work has been confined almost exclusively to the chicken; we know little about general aspects of genomes in nongame birds. This study examines the organization of a genomic region containing an Mhc class II B gene in a representative of another important lineage of the avian tree, the songbirds (Passeriformes). We used a shotgun sequencing approach to determine the sequence of a 32-kb cosmid insert containing a strongly hybridizing Mhc fragment from house finches (Carpodacus mexicanus). There were a total of three genes found on the cosmid clone, about the gene density expected for the mammalian Mhc: a class II Mhc beta-chain gene (Came-DAB1), a serine-threonine kinase, and a zinc finger motif. Frameshift mutations in both the second and third exons of Came-DAB1 and the unalignability of the gene after the third exon suggest that it is a nonfunctional pseudogene. In addition, the identifiable introns of Came-DAB1 are more than twice as large as those of chickens. Nucleotide diversity in the peptide-binding region of Came-DAB1 (Pi = 0.03) was much lower than polymorphic chicken and other functional Mhc genes but higher than the expected diversity for a neutral locus in birds, perhaps because of hitchhiking on a selected Mhc locus close by. The serine-threonine kinase gene is likely functional, whereas the zinc finger motif is likely nonfunctional. A paucity of long simple-sequence repeats and retroelements is consistent with emerging rules of chicken genomics, and a pictorial analysis of the "genomic signature" of this sequence, the first of its kind for birds, bears strong similarity to mammalian signatures, suggesting common higher-order structures in these homeothermic genomes. The house finch sequence is among a very few of its kind from nonmodel vertebrates and provides insight into the evolution of the avian Mhc and of avian genomes generally.

}, keywords = {*Avian Proteins, Animals, Base Composition, Base Sequence, Birds, Chickens, Cosmids/*genetics, Evolution, Molecular, Genes, MHC Class II/*genetics, Genetic Variation, Molecular Sequence Data, Multigene Family, Phylogeny, Proteins/genetics, Pseudogenes/*genetics, Repetitive Sequences, Nucleic Acid/genetics, Sequence Alignment, Sequence Homology, Nucleic Acid, Songbirds/*genetics}, isbn = {1088-9051 (Print)1088-9051 (Linking)}, author = {Hess, C.M. and Gasper, J. and Hoekstra, H. E. and Hill, C. E. and Edwards, S. V.} } @article {549261, title = {Multiple origins of XY female mice (genus Akodon): Phylogenetic and chromosomal evidence}, journal = {Proceedings of the Royal Society B: Biological Sciences}, volume = {267}, number = {1455}, year = {2000}, note = {

Hoekstra, H EEdwards, S VengResearch Support, Non-U.S. Gov{\textquoteright}tResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.ENGLAND2000/10/29 11:00Proc Biol Sci. 2000 Sep 22;267(1455):1825-31.

}, month = {Sep 22}, pages = {1825-31}, abstract = {

Despite the diversity in sex determination across organisms, theory predicts that the evolution of XY females is rare in mammals due to fitness consequences associated with infertility or the loss of YY zygotes. We investigated this hypothesis from a phylogenetic perspective by examining the inter- and intraspecific distribution of Y chromosomes in males and females (XY females) in South American field mice (Akodon). We found that XY females occurred at appreciable frequencies (10-66\%) in at least eight Akodon species, raising the possibility that this system of sex determination has arisen multiple times independently. To determine the number of origins of XY females in Akodon, we constructed a molecular phylogeny of 16 species of Akodon based on mitochondrial DNA control region sequences. Both parsimony and maximum-likelihood reconstruction of ancestral states suggest that multiple steps (gains or losses of XY females) best explain the evolution of XY females, but do not clearly differentiate between single and multiple origins. We then directly compared functional and non-functional Y chromosomes in six species by Southern blot analysis. We found that male and female Y chromosome restriction fragment length polymorphism patterns were identical within species, but always differed between species, providing evidence that XY females arose at least six times within the Akodon lineage. To our knowledge, this pattern in Akodon is the first documentation of a novel sex-determining system arising multiple times within a tight clade of mammals. In addition, this system provides a clear test of the accuracy of phylogenetic methods to reconstruct ancestral states.

}, keywords = {*Phylogeny, *Sex Determination Processes, Animals, Blotting, Southern, DNA, Mitochondrial/genetics, Evolution, Molecular, Female, Karyotyping, Male, Muridae/*genetics, Sex Chromosomes/genetics, Translocation, Genetic/genetics, Y Chromosome/*genetics}, isbn = {0962-8452 (Print)0962-8452 (Linking)}, author = {Hoekstra, HE and SV Edwards} }