Publications

2011
Barrett RD, Hoekstra HE. Molecular spandrels: Tests of adaptation at the genetic level. Nature Reviews Genetics 2011;12:767-80.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 'adaptive' 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 'adaptive' 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.

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2010
Robinson GE, Banks JA, Padilla DK, Burggren WW, Cohen CS, Delwiche CF, Funk V, Hoekstra HE, Jarvis ED, Johnson L, Martindale MQ, del Rio MC, Medina M, Salt DE, Sinha S, Specht C, Strange K, Strassmann JE, Swalla BJ, Tomanek L. Empowering 21st century biology. BioScience 2010;60:923-30.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.

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Hoekstra HE. Evolutionary Biology: The Next 150 years. In: Bell MA, Futuyma DA, Eanes WF, Levinton JS Evolution Since Darwin: The First 150 Years. Sunderland, MA: Sinauer Press; 2010 PDF
Hoekstra HE. From Darwin to DNA: The genetic basis of color adaptation. In: Losos JB In the Light of Evolution: Essays from the Laboratory and Field. Greenwood Village, CO: Roberts and Co. Publishers; 2010 PDF
Hoekstra HE. In search of the elusive behavior gene. In: Grant P, Grant R Search for the Causes of Evolution: From Field Observations to Mechanisms. Princeton, NJ: Princeton University Press; 2010
Fisher HS, Hoekstra HE. Competition drives cooperation among closely related sperm of deer mice. Nature 2010;463:801-3.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.

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Manceau M, Domingues VS, Linnen CR, Rosenblum EB, Hoekstra HE. Convergence in pigmentation at multiple levels: mutations, genes and function. Philosophical Transactions of the Royal Society 2010;365:2439-50.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'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.

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Weber JN, Peters MB, Tsyusko OV, Linnen CR, Hagen C, Schable NA, Tuberville TD, McKee AM, Lance SL, Jones KL, Fisher HS, Dewey MJ, Hoekstra HE, Glenn TC. Five hundred microsatellite loci for Peromyscus. Conservation Genetics 2010;11:1243-46.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.

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Chuong EB, Tong W, Hoekstra HE. Maternal-fetal conflict: Rapidly evolving proteins in the rodent placenta. Molecular Biology and Evolution 2010;27:1221-5.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.

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Linnen CR, Hoekstra HE. Measuring natural selection on genotypes and phenotypes in the wild. Cold Spring Harbor Symposia on Quantitative Biology 2010;74:155-68.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.

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Rosenblum EB, Rompler H, Schoneberg T, Hoekstra HE. Molecular and functional basis of phenotypic convergence in white lizards at White Sands. PNAS 2010;107:2113-7.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.

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Turner LM, Young AR, Rompler H, Schoneberg T, Phelps SM, Hoekstra HE. Monogamy evolves through multiple mechanisms: Evidence from V1aR in deer mice. Molecular Biology and Evolution 2010;27:1269-78.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' 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.

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Hull JM, Mindell DP, Talbot SL, Kay EH, Hoekstra HE, Ernest HB. Population structure and plumage polymorphism: The intraspecific evolutionary relationships of a polymorphic raptor, Buteo jamaicensis harlani. BMC Evolutionary Biology 2010;10:224.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.

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Vignieri SN, Larson JG, Hoekstra HE. The selective advantage of crypsis in mice. Evolution 2010;64:2153-8.Abstract

The light color of mice that inhabit the sandy dunes of Florida'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.

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Metz HC, Manceau M, Hoekstra HE. Turing patterns: How the fish got its spots. Pigment Cell & Melanoma Research 2010;24:12-4. PDF
Hubbard JK, Uy JA, Hauber ME, Hoekstra HE, Safran RJ. Vertebrate pigmentation: From underlying genes to adaptive function. Trends in Genetics 2010;26:231-9.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?

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2009
Weber JN, Hoekstra HE. The evolution of burrowing behavior in deer mice. Animal Behavior 2009;77:603-09.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 ‘complex’ 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.

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Hoekstra HE. The Evolution Ringmaster: Review of The Greatest Show on Earth: The Evidence for Evolution by Richard Dawkins. Cell 2009;139:454-55. PDF
Berry AJ, Hoekstra HE. (Re)Reading The Origin. Current Biology 2009;19(3):R9. PDF
Mullen LM, Vignieri SN, Gore JA, Hoekstra HE. Adaptive basis of geographic variation: Genetic, phenotypic and environmental differences among beach mouse populations. Proceedings of the Royal Society B: Biological Sciences 2009;276:3809-18.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's Gulf Coast. However, much less is known about differentiation among the Gulf Coast beach mice, which comprise five subspecies linearly arrayed on Florida'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 'lightness' 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.

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