Publications

Publications

Kingsley EP, Kozak KM, Pfeifer SP, Yang D-S, Hoekstra HE. The ultimate and proximate mechanisms driving the evolution of long tails in forest deer mice. Evolution 2017;71(2):261-273.Abstract
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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 — either independently or together — are adaptive.

 

Kautt AF, Chen J, Lewarch CL, Hu C, Turner K, Lassance J-M, Baier F, Bedford NL, Bendesky A, Hoekstra HE. Evolution of gene expression across brain regions in behaviourally divergent deer mice. Molecular Ecology 2024;(e17270)Abstract
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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)—which differ in a range of innate behaviours, including their social system—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 (52–59% 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.
Khadraoui M, Merritt JR, Hoekstra HE, Bendesky A. Post-mating parental behavior trajectories differ across four species of deer mice. PLoS ONE 2022;17(10):e0276052.Abstract
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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.
Harringmeyer OS, Hoekstra HE. Massive inversion polymorphisms shape the genomic landscape of deer mice. Nature Ecology & Evolution 2022;6:1965–1979.Abstract
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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 (1.5–43.8 Mb) and cause near-complete suppression of recombination when heterozygous (0–0.03 cM Mb−1). We found that inversion breakpoints frequently occur in centromeric and telomeric regions and are often flanked by long inverted repeats (0.5–50 kb), suggesting that they probably arose via ectopic recombination. By genotyping inversions in populations across the species’ 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.
Hoekstra HE, Robinson GE. Behavioral genetics and genomics: Mendel’s peas, mice,and bees. PNAS 2022;119(30):e21221541119.Abstract
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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 ’ s remarkable discovery of “ inheritance factors, ” 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.
Bedford NL, Weber JN, Tong W, Baier F, Kam A, Greenberg RA, Hoekstra HE. Interspecific variation in cooperative burrowing behavior by Peromyscus mice. Evolution Letters 2022;https://doi.org/10.1002/evl3.293Abstract
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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.
Kingsley EP, Hager ER, Lassance J-M, Tuner KM, Harringmeyer OS, Kirby C, Neugebroen BI, Hoekstra HE. Adaptive tail-length evolution in deer mice is associated with differential Hoxd13 expression in early development. bioRxiv Forthcoming;Abstract
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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.
Wooldridge TB, Kautt AF, Lassance JM, McFadden S, Domingues VS, Mallarino R, Hoekstra HE. A novel enhancer of Agouti contributes to parallel evolution of cryptically colored beach mice. PNAS 2022;119(27):e220286119.Abstract
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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 ’ 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.
Hu CK, York RA, Metz HC, Bedford NL, Fraser HB, Hoekstra HE. Cis-regulatory changes in locomotor genes are associated with the evolution of burrowing behavior. Cell Reports 2022;38:110360.Abstract
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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.
Hager ER, Hoekstra HE. Tail length evolution in deer mice: linking morphology, behavior and function. Integrative and Comparative Zoology 2021;61(2)Abstract
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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.

Hager ER, Harringmeyer OS, Wooldridge TB, Theingi S, Gable JT, McFadden S, Neugeboren B, Turner KM, Hoekstra HE. A chromosomal inversion contributes to divergence in multiple traits between deer mouse ecotypes. Science 2022;377 (6604):399-405.Abstract
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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—tail length and coat color—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.
Jourjine N, Hoekstra HE. Expanding evolutionary neuroscience: insights from comparing variation in behavior. Neuron 2021;2(11):1084-1099.Abstract
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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, “nontraditional” 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.
Harringmeyer OS, Woolfolk ML, Hoekstra HE. Fishing for the genetic basis of migratory behavior. Cell 2021;184(2):303-305.Abstract
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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 “simple” phenotype.
Lewandowski JP, Dumbović G, Watson AR, Hwang T, Jacobs-Palmer E, Chang N, Much C, Turner K, Kirby C, Schulz JF, Muller C-L, Rubenstein ND, Groff AF, Liapis SC, Gerhardinger C, Hubner N, van Heesch S, Hoekstra HE, Sauvageau M, Rinn JL. The Tug1 locus is essential for male fertility. Genome Biol. 2020;21(1):237.Abstract
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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.
Barrett RDH, Laurent S, Mallarino R, Pfeifer SP, Xu CCY, Foll M, Wakamatsu K, Duke-Cohan JS, Jensen JD, Hoekstra HE. Linking a mutation to survival in wild mice. Science 2019;363:499-504.Abstract
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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.
Kocher SD, Mallarino R, Rubin BER, Yu DW, Hoekstra HE, Pierce NE. The genetic basis of a social polymorphism in halictid bees. Nature Communications 2018;9:4338.Abstract
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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.
Baier F, Hoekstra HE. The genetics of morphological and behavioral island traits in deer mice. Proceedings of the Royal Society B 2019;286:20191697.Abstract
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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.
Delaney EK, Hoekstra HE. Diet-based assortative mating through sexual imprinting. Ecology & Evolution 2019;00:1-6.Abstract
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Speciation is facilitated by “magic traits,” 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.

Fisher HS, Hook KA, Weber WD, Hoekstra HE. Sibling rivalry: Males with more brothers develop larger testes. Ecology and Evolution 2018;8(16):8197-8203.Abstract
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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.
Goncalves GL, Masestri R, Moreira GRP, Jacobi MAM, Freitas TRO, Hoekstra HE. Divergent genetic mechanisms lead to spiny hair in mammals. PLoS ONE 2018;13(8):e0202219.Abstract
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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.
Lewarch CL, Hoekstra HE. The evolution of nesting behaviour in Peromyscus mice. Animal Behaviour 2018;139:103-115.Abstract
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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.

Metz HC, Bedford NL, Pan L, Hoekstra HE. Evolution and genetics of precocious burrowing behavior in Peromyscus mice. Current Biology 2017;27:3837-3845.Abstract
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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.
Pfeifer SP, Laurent S, Sousa VC, Linnen CR, Foll M, Excoffier L, Hoekstra HE, Jensen JD. The evolutionary history of Nebraska deer mice: local adaptation in the face of strong gene flow. Molecular Biology and Evolution 2018;35:792-806.Abstract
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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.