Our research focuses on understanding how genetic variation is generated and maintained in natural populations. By identifying genes contributing to adaptive phenotypic variation, we can use population and ecological genetics to gain insight into the evolutionary process.


For example, we use population genetics to:

(1) estimate the age of adaptive alleles

(2) to estimate the strength of selection using patterns of nucleotide variation

(3) predict the order in which alleles were selected

(4) detemine if adaptive alleles were derived from standing genetic variation or new mutations.


We also use an ecological genetic approach by studying the spatial and temporal distribution of alleles. Thus, in addition to genetic crosses done in the laboratory, we study natural populations in the field. We have complementary projects focusing on:

(1) ecological genetics of clinal variation in pigmentation and skeletal morphology using museum skins collected in the 1920's

(2) population genetics and phylogeography of Peromyscus polionotus populations in the southwestern U.S.

(3) conservation genetics of endangered beach mouse subspecies.


Field work

Our lab takes advantage of phenotypic variation in natural populations of Peromyscus. Here, Cynthia Steiner and Jeff Gore are live trapping beach mice on the Barrier Islands in the Gulf Coast of Florida (April 2005). Our lab has several field sites including in Florida, Nebraska, Bulgaria, South Carolina and New Mexico. We have recently begun collaborative work with researchers in Brazil. By examining populations occupying similar environments in diverse locales, we can ask if similar or different genetic mechanisms underlie convergent phenotypes. (Photo credit: Lynne Mullen, Harvard)


Natural history collections

Hoekstra and MiceNatural history museums are repositories of morphological and distributional information. Museum specimens of Peromyscus polionotus date back to the late 1800's, but the most extensive collections belong to Francis Sumner from his surveys of Peromyscus populations in the 1920's. His classic studies on intraspecific variation laid the groundwork for our own research.


Museum specimens provide us with phenotypic data from known locations. In addition, we are able to extract DNA from these specimens using ancient DNA techniques. Thus, we can take advantage of hundreds of specimens from extant species as well as species that have gone extinct in historical time. These collections also allow us to incorporate a temporal component to our research, enabling us to document changes in both genetic and phenotypic variation over time.


We are part of the Museum of Comparative Zoology (MCZ) at Harvard University. Our collections are accessioned in the Mammal Department and are available to researchers throughout the world. The MCZ Mammal Collection is one of the largest historic, geographic, and taxonomically diverse university systematic collections in the world.


and Development

Genetics, development and evolution of color and patterning

Our lab is working to understand the genetic and developmental basis of adaptive color variation in natural popuations of mammals. Using genetic mapping and association studies to uncover the genomic regions, and ultimately the genes and mutations, involved in phenotypic differentiation. These studies will allow us to address several fundamental questions abut evolutionary change: How many genes contribute to adaptive variation? Are the same genomic regions or different regions responsible for convergent phenotypes? Are these changes in regulatory or structural regions, and do they affect gene expression or protein function? What is the role of epistasis in adaptation?

Adaptive differentiation in beach mice

Hoekstra and MiceThe Santa Rosa Island beach mouse (Peromyscus polionotus leucocephalus) and the oldfield mouse (P. p. subgriseus) from mainland Florida differ pigmentation and patterning -- each are cryptically colored in their native habitat. We are using QTL mapping techniques, candidate genes and functional assays to identify the molecular basis of phenotypic differentiation. (Photo credit: Clint Cook)




Development of color pattern

Hoekstra and MiceWe are also interested in how changes during development can lead to different adult color patterns. To this end, we are studying melanocyte development, proliferation, migration and differentiation using in situ hybridization and immunohistochemstry techniques. Here you can see a Peromyscus DAPI-stained hair follicle with melanocytes stained in green. (Photo credit: Marie Manceau, Harvard)




Molecular basis of crypsis

Hoekstra and MiceDeer mice inhabiting the Sandhills of Nebraska have unique banding patterns on their dorsal hairs which give them an overall golden color and make them camouflaged from visual predators. We conduct fieldwork, which includes catching mice in live traps, to study the phylogeographic and evolutionary history of these unique populations. Using a combination of classical, molecular and population genetics, we are also working to understand the molecular basis of color adaptation in these mice. (Photo credit: Evan Kingsley, Harvard)





Behavioral Genetics

Genetic architecture and evolution of behavior

We are interested in the genetic basis of naturally occurring behaviors. Presently we are focusing our investigations on two primary behaviors: burrowing behavior and mate choice/mating system. First, we are studying the genetic basis of mate choice and mating system in Peromyscus using a forward genetics approach (i.e., genetic crosses of species that vary in behaviors). Using a similar approach, we are exploring the genetics of innate burrow-building between two sister species of Peromyscus that differ in their burrow design. In both of these projects, we are characterizing the genetic architecture of behavior. We ask the following questions: How many and which genes contribute to behavioral adaptation? Do adaptive behaviors and morphologies have similar genetic architectures? Do adaptive behaviors have a large genetic component? Is behavioral variation controlled by changes in gene regulation?


To better understand the evolutionary dynamics of behavioral evolution, we are also investigating:

(1) the prevalence and causes of behavioral variation in nature

(2) the evolution of behaviorial traits among closely related species of Peromyscus.

Evolution of burrowing

Hoekstra and MiceDifferent species of Peromyscus build dramatically different burrows. These burrowing behaviors are largely innate, and can be assayed under controlled laboratory conditions, allowing us to focus on the genetic contribution to species-specific burrowing. More generally, we are interested in identifying the genetic regions and genes that contribute to adaptive behaviors in natural populations. (Image credit: Wallace Dawson)



Genetic architecture of social behavior

Hoekstra and MicePeromyscus species also differ in their mating system, ranging from highly monogamous to promiscuous. We are examing the genetic basis of social behaviors between closely related species of Peromyscus. Specifically, we are interested in how behaviors differ between males from species with different social structures. This project will also help us understand the genetic basis of sex-specific behaviors and how they evolve. (Photo credit: Adrian Young, Harvard)




Sexual Selection

Genetics of sexually selected traits


Hoekstra and MiceTaking advantage of the diversity of mating systems in the genus Peromyscus, our lab is studying the genetic architecture of reproductive traits influenced by sexual selection. Specifically, we are investigating (1) how individuals achieve fertilization success in a competitive environment, (2) the molecular underpinnings of these adaptive reproductive traits and (3) their evolutionary history. Our current work focuses on male reproductive traits including sperm production, morphology, swimming performance, and cooperative behavior.




Ecological Speciation

Genetics of reproductive isolation

Our lab is interested in understanding the genetic basis of reproductive isolation in natural populations. Peromyscus is a particularly appropriate group because of the wealth of information on speciation, including a wealth of genetic crosses between species that show a range of reproductive isolation. In addition, there exists well-characterized variation in Peromyscus mating systems, which allows us to address the role of mating system (sperm competition and sexual conflict). Ultimately, we are interested in mapping genetic regions involved in reproductive isolation between different pairs of Peromyscus species.

Gametic isolation

Hoekstra and MiceWe are currently exploring the evolution of reproductive proteins within and between Peromyscus species. Using a combination of testis-expressed ESTs and candidate genes, we are uncovering the evolution, molecular basis and functional consequences of mutations in fertilization proteins (specifically, sperm-egg interactions). Specifically, we are interested in the evolutionary forces acting on these proteins and how variation in these proteins potentially contribute to reproductive isolation. (Image credit: Leslie Turner)




Sexual isolation

Taking advantage of the diversity of mating systems in the genus Peromyscus, our lab is studying the genetic architecture of reproductive traits influenced by sexual selection. Specifically, we are investigating the molecular underpinnings of male reproductive traits that are correlated with mating system such as sperm morphology and performance. (Photo credit: Pascal Gagneux).


Behavioral isolation

Hoekstra and MiceSome sister species of Peromyscus can produce viable and fertile in the lab, but rarely produce hybrids in the wild, even when sympatric. These mice exhibit strong mating preference for conspecifics. We are interested in uncovering the genetic basis of mate choice in these species pairs and in particular understanding the role of natural selection in the evolution of mate choice.





New projects

There are several new projects being started in the lab that include the functional effects of amino acid mutations in receptors within and between species (Holger Roempler), developmental genetics of tail length variation in Peromyscus (Evan Kingsley), the evolution of cooperative behavior in sperm (Heidi Fisher), the evolution and development of stripes in chipmunks (Hillery Metz and Marie Manceau), and experimental genomics to study adaptation (Rowan Barrett). While many of us use Peromyscus as a model system, we are also starting projects with natural populations of house mice and other rodents including chipmunks, striped mice and zebra mice.