Biology subjects

Hoekstra, H.

Publications and source records attributed to Hoekstra, H..

5 recordsLinked to original sources

bioRxiv2026

Pangenome graphs reveal the extent and complexity of genetic variation in North America's most abundant mammal

Pangenome methods reduce reference bias and enable the characterization of previously inaccessible genomic variation within a species, and are thus especially useful for species with high levels of genetic diversity. Here, we constructed a pangenome for the deer mouse (Peromyscus maniculatus), a model for studying local adaptation and a potent reservoir for diverse zoonotic diseases, using long-read assemblies from 14 ecologically and biogeographically diverse populations and 2 outgroup species (totaling 19 haplotypes). The total length of the pangenome is 3.9 Gb, but only 1.4 Gb is shared across all haplotypes, suggesting vast structural diversity. From this pangenome we identified [~]108.3 million single nucleotide polymorphisms (SNPs), [~]23.9 million indels (variants < 50 bp), and [~]2.4 million structural variants (variants > 50 bp) as well as complex genetic variation driven by massive chromosomal rearrangements and an unprecedented diversity of centromeric satellite positions. Furthermore, we uncover widespread gene copy number variation (CNVs)-some genes vary in number by an order of magnitude across deer mouse haplotypes-in addition to several gene-rich loci that display high levels of structural diversity. Such genes are enriched for functions related to sensory perception, environmental interaction, and immune responses and many display signatures of positive selection at the molecular level, suggesting functional diversification. Our work provides important insight into the utility of pangenomes for genetically diverse species and illuminates underappreciated genomic plasticity within a mammalian species.

evolutionary biology↗

bioRxiv2024

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

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.

evolutionary biology↗

bioRxiv2023

The neural basis of defensive behaviour evolution in Peromyscus mice

Evading imminent predator threat is critical for survival. Effective defensive strategies can vary, even between closely related species. However, the neural basis of such species-specific behaviours is still poorly understood. Here we find that two sister species of deer mice (genus Peromyscus) show different responses to the same looming stimulus: P. maniculatus, which occupy densely vegetated habitats, predominantly dart to escape, while the open field specialist, P. polionotus, pause their movement. This difference arises from species-specific escape thresholds, is largely context-independent, and can be triggered by both visual and auditory threat stimuli. Using immunohistochemistry and electrophysiological recordings, we find that although visual threat activates the superior colliculus in both species, the role of the dorsal periaqueductal gray (dPAG) in driving behaviour differs. While dPAG activity scales with running speed and involves both excitatory and inhibitory neurons in P. maniculatus, the dPAG is largely silent in P. polionotus, even when darting is triggered. Moreover, optogenetic activation of excitatory dPAG neurons reliably elicits darting behaviour in P. maniculatus but not P. polionotus. Together, we trace the evolution of species-specific escape thresholds to a central circuit node, downstream of peripheral sensory neurons, localizing an ecologically relevant behavioural difference to a specific region of the complex mammalian brain.

neuroscience↗

bioRxiv2021

Cis-regulatory changes in locomotor genes are associated with the evolution of burrowing behavior

How evolution modifies complex, innate behaviors is largely unknown. Divergence in many morphological traits has been linked, at least in part, to cis-regulatory changes in gene expression, a pattern also observed in some behaviors of recently diverged populations. Given this, we compared the gene expression in the brains of two interfertile sister species of Peromyscus mice, including allele-specific expression (ASE) of their F1 hybrids, that show large and heritable differences in burrowing behavior. Because cis-regulation may contribute to constitutive as well as activity-dependent gene expression, we also captured a molecular signature of burrowing circuit divergence by quantifying gene expression in mice shortly after burrowing. We found that several thousand genes were differentially expressed between the two sister species regardless of behavioral context, with several thousand more showing behavior-dependent differences. Allele-specific expression in F1 hybrids showed a similar pattern, suggesting that much of the differential expression is driven by cis-regulatory divergence. Genes related to locomotor coordination showed the strongest signals of lineage-specific selection on burrowing-induced cis-regulatory changes. By comparing these candidate genes to independent quantitative trait locus (QTL) mapping data, we found that the closest QTL markers to these candidate genes are associated with variation in burrow shape, demonstrating an enrichment for candidate locomotor genes near segregating causal loci. Together, our results provide insight into how cis-regulated gene expression can depend on behavioral context as well as how this dynamic regulatory divergence between species can be integrated with forward genetics to enrich our understanding of the genetic basis of behavioral evolution.

animal behavior and cognition↗

bioRxiv2021

Binocular Mirror-Symmetric Microsaccadic Sampling of Hyperacute 3D-Vision

Neural mechanisms behind stereopsis, which requires simultaneous disparity inputs from two eyes, have remained mysterious. Here we show how ultrafast mirror-symmetric photomechanical contractions in the frontal forward-facing left and right eye photoreceptors give Drosophila super-resolution 3D-vision. By interlinking multiscale in vivo assays with multiscale simulations, we reveal how these photoreceptor microsaccades - by verging, diverging and narrowing the eyes overlapping receptive fields - channel depth information, as phasic binocular image motion disparity signals in time. We further show how peripherally, outside stereopsis, microsaccadic sampling tracks a flying flys optic flow field to better resolve the world in motion. These results change our understanding of how insect compound eyes work and suggest a general dynamic stereo-information sampling strategy for animals, robots and sensors. Significance statementTo move efficiently, animals must continuously work out their x,y,z-positions in respect to real-world objects, and many animals have a pair of eyes to achieve this. How photoreceptors actively sample the eyes optical image disparity is not understood because this fundamental information-limiting step has not been investigated in vivo over the eyes whole sampling matrix. This integrative multiscale study will advance our current understanding of stereopsis from static image disparity comparison to a new morphodynamic active sampling theory. It shows how photomechanical photoreceptor microsaccades enable Drosophila super-resolution 3D-vision and proposes neural computations for accurately predicting these flies depth-perception dynamics, limits, and visual behaviors.

neuroscience↗