About

Hopi E. Hoekstra is the Edgerley Family Dean of the Faculty of Arts and Sciences at Harvard University, holding the C.Y. Chan Professorship of Arts and Sciences and the Xiaomeng Tong and Yu Chen Professorship of Life Sciences. She is also a Senior Fellow of the Society of Fellows, ex officio. Her research focuses on understanding how variation is generated and maintained in natural populations, with particular interest in the proximate (molecular, genetic, developmental mechanisms) and ultimate (timing, strength, agent of selection) causes of evolutionary change. Hoekstra's work aims to identify and characterize the molecular changes responsible for traits that affect organismal fitness in the wild, primarily studying natural populations of mammals. Her interdisciplinary approach combines molecular techniques, population-genetic tests, classical genetic crosses, behavioral assays, and field experiments to explore the evolution of morphological, behavioral, and reproductive diversity.

Research topics

• Biology
• Evolutionary biology
• Genetics
• Ecology
• Paleontology
• Cognitive psychology
• Psychology
• Neuroscience
• Cognitive science

Selected publications

• An X-to-autosome-to-Y chromosome amplified retrogene family functions in spermatids

  Current Biology · 2026-05-01

  article
  PublisherDOI

• Pleistocene climatic oscillations impact the diversification of deer mice ( <i>Peromyscus maniculatus)</i> and the independent evolution of ecotypes

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-01-27

  articleOpen accessSenior author

  Abstract A central question in evolutionary biology is whether local adaptation is predictable when a species repeatedly encounters similar environments. The deer mouse, Peromyscus maniculatus , has a range of over 13 million km 2 in North America and may be found in nearly every terrestrial habitat. Because of their abundance and wide habitat preference, deer mice and closely related Peromyscus , which we refer to as the P. maniculatus species complex, are at the forefront of studies of biogeography and local adaptation. Here, we undertake a comprehensive survey of genome-wide and phenotypic diversity to characterize the recent evolutionary history of this group. We sequenced whole genomes from 232 individuals across their range, representing the most thorough genetic sampling of the P. maniculatus species complex to date. We identify six geographically delineated clades, several of which encompass both classically recognized P. maniculatus subspecies as well as other recognized species. Ecological niche modelling suggests that this geographic structure resulted from rapid post-LGM range expansion and adaptation to emerging habitats. Our morphological measurements of 979 specimens and field data compiled from over 28,000 museum records show that deer mice in forests across the range consistently have longer tails, larger feet, bigger ears, and elongated whiskers. These traits constitute an arboreal ecotype that has evolved at least three times independently, and was likely lost in other parts of the range as populations moved out of forested habitat. Altogether, these results suggest that post-LGM increases in forested habitat drove the parallel evolution of arboreal ecotypes across the deer mouse range.

  PublisherOA PDFDOI

• Author response: Cellular evolution of the hypothalamic preoptic area of behaviorally divergent deer mice

  2025-04-07

  peer-reviewOpen accessSenior author

  Single-nucleus RNA-sequencing of the hypothalamic preoptic area of monogamous and promiscuous deer mouse species reveals neuronal differences that may be responsible for innate changes in mating and parental care behavior.

  PublisherDOI

• Cellular evolution of the hypothalamic preoptic area of behaviorally divergent deer mice

  eLife · 2025-02-27

  preprintOpen accessSenior author

  Abstract Genetic variation is known to contribute to the variation of animal social behavior, but the molecular mechanisms that lead to behavioral differences are still not fully understood. Here, we investigate the cellular evolution of the hypothalamic preoptic area (POA), a brain region that plays a critical role in social behavior, across two sister species of deer mice (Peromyscus maniculatus and P. polionotus) with divergent social systems. These two species exhibit large differences in mating and parental care behavior across species and sex. Using single-nucleus RNA-sequencing, we build a cellular atlas of the POA for males and females of both Peromyscus species. We identify four cell types that are differentially abundant across species, two of which may account for species differences in parental care behavior based on known functions of these cell types. Our data further implicate two sex-biased cell types to be important for the evolution of sex-specific behavior. Finally, we show a remarkable reduction of sex-biased gene expression in P. polionotus, a monogamous species that also exhibits reduced sexual dimorphism in parental care behavior. Our POA atlas is a powerful resource to investigate how molecular neuronal traits may be evolving to give rise to innate differences in social behavior across animal species.

  PublisherDOI

• Cellular evolution of the hypothalamic preoptic area of behaviorally divergent deer mice

  eLife · 2025-04-07 · 5 citations

  articleOpen accessSenior author

  Genetic variation is known to contribute to the variation of animal social behavior, but the molecular mechanisms that lead to behavioral differences are still not fully understood. Here, we investigate the cellular evolution of the hypothalamic preoptic area (POA), a brain region that plays a critical role in social behavior, across two sister species of deer mice ( Peromyscus maniculatus and P. polionotus ) with divergent social systems. These two species exhibit large differences in mating and parental care behavior across species and sex. Using single-nucleus RNA-sequencing, we build a cellular atlas of the POA for males and females of both Peromyscus species. We identify four cell types that are differentially abundant across species, two of which may account for species differences in parental care behavior based on known functions of these cell types. Our data further implicate two sex-biased cell types to be important for the evolution of sex-specific behavior. Finally, we show a remarkable reduction of sex-biased gene expression in P. polionotus , a monogamous species that also exhibits reduced sexual dimorphism in parental care behavior. Our POA atlas is a powerful resource to investigate how molecular neuronal traits may be evolving to give rise to innate differences in social behavior across animal species.

  PublisherDOI

• Evolutionary expansion of the corticospinal system is linked to dexterity in <i>Peromyscus</i> mice

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-17 · 2 citations

  preprintOpen accessSenior author

  Abstract While the central nervous system is perpetually reshaped by evolution, the principles governing how such changes promote ecologically relevant behaviors without breaking established functions are poorly understood. The expansion of neuron number is a potential mechanism by which the nervous system evolves to support changes in behavior without disrupting existing circuit function. Corticospinal neurons (CSNs) are a classic example: an expansion in the corticospinal system in the primate lineage has been hypothesized to underlie their exceptional dexterity. However, the role of CSN number in behavior has been difficult to assess due to the lack of a tractable model system. We compared two closely related subspecies of deer mice ( Peromyscus maniculatus ): forest mice, which evolved the ability to adeptly climb, presumably to support a semi-arboreal lifestyle, and prairie mice, which are less proficient climbers. We find that forest mice have about two-fold larger corticospinal tracts (CSTs) driven by an increase in CSN number in secondary motor and sensory cortical areas (M2 and S2). Furthermore, forest mice display greater manual dexterity than their prairie counterparts in a reach-to-grasp task, consistent with the idea that an increase in CSN number supports more dexterous behavior. High-throughput neural recordings during this task revealed a difference in the timing of neural activity between forest and prairie mice, specifically in M2: in forest mice, the peak of activity was shifted towards the grasping phase of the behavior. Forest mice also outperform their prairie counterparts on an ecologically relevant climbing task, where they spend more time upright crossing a thin rod, move faster, and right themselves more quickly when they fall, suggesting a general difference in motor dexterity not restricted to hand use. Finally, we use F2 hybrid animals to show that CST size is correlated with climbing dexterity, providing support for the long-standing hypothesis that corticospinal system expansion supports the evolution of dexterity. Together, our work establishes the forest-prairie deer mouse system as a model to investigate the role of neuron number expansion, and CSNs in particular, in dexterous movement.

  PublisherOA PDFDOI

• Author response: Cellular evolution of the hypothalamic preoptic area of behaviorally divergent deer mice

  2025-02-27

  peer-reviewOpen accessSenior author

  Genetic variation is known to contribute to the variation of animal social behavior, but the molecular mechanisms that lead to behavioral differences are still not fully understood. Here, we investigate the cellular evolution of the hypothalamic preoptic area (POA), a brain region that plays a critical role in social behavior, across two sister species of deer mice (Peromyscus maniculatus and P. polionotus) with divergent social systems. These two species exhibit large differences in mating and parental care behavior across species and sex. Using single-nucleus RNA-sequencing, we build a cellular atlas of the POA for males and females of both Peromyscus species. We identify four cell types that are differentially abundant across species, two of which may account for species differences in parental care behavior based on known functions of these cell types. Our data further implicate two sex-biased cell types to be important for the evolution of sex-specific behavior. Finally, we show a remarkable reduction of sex-biased gene expression in P. polionotus, a monogamous species that also exhibits reduced sexual dimorphism in parental care behavior. Our POA atlas is a powerful resource to investigate how molecular neuronal traits may be evolving to give rise to innate differences in social behavior across animal species.

  PublisherDOI

• The genomic imprint of chromosomal inversions and demographic history in island populations of deer mice

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-04-22

  preprintOpen access

  ABSTRACT Populations that colonize islands experience novel selective pressures, fluctuations in size, and changes to their connectivity. Owing to their unique geographic setting, islands can function as natural laboratories in which to examine the interactions between demographic history and natural selection replicated across isolated populations. We used whole genome sequences of wild-caught deer mice ( Peromyscus maniculatus ) from two islands (Saturna and Pender) and one mainland location (Maple Ridge) in the Gulf Islands region of coastal British Columbia to investigate two primary determinants of genome-wide diversity: chromosomal inversions and non-equilibrium demographic history. We found that segregating inversions produce characteristic, large-scale distortions in allele frequencies and linkage disequilibrium that make it possible to identify and characterize them from short-read sequence data. Patterns of variation within and between karyotypes indicate that six inversion polymorphisms have been maintained by a shared history of balancing selection in both island and mainland populations. Whereas the estimated timing of contemporary population splits is consistent with the isolation of island populations from each other following the Last Glacial Maximum, ancestral island and mainland lineages are inferred to have diverged much earlier. These aspects of demographic history suggest that shared inversions existed long ago in a common ancestor or spread via limited gene flow between ancestral island and mainland lineages. Our results raise the possibility that inversions segregating among Gulf Islands populations are on similar evolutionary trajectories, providing a contrast to previous findings in mainland P. maniculatus and contributing to the emerging portrait of inversion evolution in this species.

  PublisherOA PDFDOI

• How repeats rearrange chromosomes: The molecular basis of chromosomal inversions in deer mice

  Cell Reports · 2025-05-01 · 11 citations

  articleOpen accessSenior author

  Large genomic rearrangements, such as chromosomal inversions, can play a key role in evolution, but the mechanisms by which these rearrangements arise remain poorly understood. To study the origins of inversions, we generated chromosome-level de novo genome assemblies for four subspecies of the deer mouse (Peromyscus maniculatus) with known inversion polymorphisms. We identified ∼8,000 inversions, including 47 megabase-scale inversions, that together affect ∼30% of the genome. Analysis of inversion breakpoints suggests that while most small (<1 Mb) inversions arose via ectopic recombination between retrotransposons, large (>1 Mb) inversions are primarily associated with segmental duplications (SDs). Large inversion breakpoints frequently occur near centromeres, which may be explained by an accumulation of retrotransposons in pericentromeric regions driving SDs. Additionally, multiple large inversions likely arose from ectopic recombination between near-identical centromeric satellite arrays located megabases apart, suggesting that centromeric repeats may also facilitate inversions. Together, our results illuminate how repeats give rise to massive shifts in chromosome architecture.

  PublisherOA PDFDOI

• The Genomic Imprint of Chromosomal Inversions and Demographic History in Island Populations of Deer Mice

  Molecular Biology and Evolution · 2025-10-04

  articleOpen access

  Populations that colonize islands experience novel selective pressures, fluctuations in size, and changes to their connectivity. Owing to their unique geographic setting, islands can function as natural laboratories in which to examine the interactions between demographic history and natural selection replicated across isolated populations. We used whole genome sequences of wild-caught deer mice (Peromyscus maniculatus) from two islands (Saturna and Pender) and one mainland location (Maple Ridge) in the Gulf Islands region of coastal British Columbia to investigate two primary determinants of genome-wide diversity: chromosomal inversions and non-equilibrium demographic history. We found that segregating inversions produce characteristic, large-scale distortions in allele frequencies and linkage disequilibrium that make it possible to identify and characterize them from short-read sequence data. Patterns of variation within and between karyotypes indicate that six inversion polymorphisms have been maintained by a shared history of balancing selection in both island and mainland populations. Whereas the estimated timing of contemporary population splits is consistent with the isolation of island populations from each other following the Last Glacial Maximum, ancestral island and mainland lineages are inferred to have diverged much earlier. These aspects of demographic history suggest that shared inversions existed long ago in a common ancestor or spread via limited gene flow between ancestral island and mainland lineages. Our results raise the possibility that inversions segregating among Gulf Islands populations are on similar evolutionary trajectories, providing a contrast to previous findings in mainland P. maniculatus and contributing to the emerging portrait of inversion evolution in this species.

  PublisherOA PDFDOI

Recent grants

• Genetic Architecture of Peromyscus Coloration

  NSF · $418k · 2004–2007

• DISSERTATION RESEARCH: The genetic basis of adaptive burrowing behavior

  NSF · $15k · 2009–2011

• Evolution, Genetics and Development: The Origin of Adaptive Pigment Alleles in Beach Mice

  NSF · $600k · 2009–2012

• Molecular and Functional Basis of Agouti Camouflage in Peromyscus Populations

  NSF · $300k · 2007–2009

• DISSERTATION RESEARCH: Behavioral and genomic evidence for reproductive isolation between two sister species of Peromyscus

  NSF · $15k · 2011–2013

Frequent coauthors

• Jean‐Marc Lassance

  Howard Hughes Medical Institute

  40 shared

• Nicole L. Bedford

  University of Wyoming

  35 shared

• Olivia S. Harringmeyer

  Harvard University

  34 shared

• Heidi S. Fisher

  Jackson Laboratory

  33 shared

• Jeffrey D. Jensen

  Arizona State University

  30 shared

• Ricardo Mallarino

  Princeton University

  28 shared

• Kyle M. Turner

  Harvard University

  27 shared

• Emily Jacobs-Palmer

  University of Washington

  25 shared

Labs

• Hoekstra LabPI

Education

• B.A., Molecular and Cell Biology

  University of California, Berkeley

  1993

• Ph.D., Molecular and Cell Biology

  University of California, Berkeley

  1998

Awards & honors

• Senior Fellow of the Society of Fellows