Research
Research Interests
I am broadly interested in understanding the genomic basis and evolution of complex adaptations. My work typically combines functional, comparative, and population genomic data to identify the mechanisms underlying unique traits and investigate the evolutionary processes by which they arose. I am particularly interested in understanding how gene regulatory architecture contributes to the evolution of novel traits, drives rapid adaptation, and underlies phenotypic variation in natural populations.
As highlighted below, my work leverages unique and non-traditional model systems to address broad evolutionary questions and provide insight into the mechanisms and regulation of extreme vertebrate adaptations.
Regulation and evolution of snake venom systems
The evolution of novel genes and organ systems often necessitates the evolution or modification of gene regulatory mechanisms. These mechanisms may evolve from existing non-regulatory sequences, be co-opted from existing regulatory machinery, or a combination of both. Understanding how regulatory architecture evolves is therefore crucial for understanding the processes that drive the evolution of novel biological systems and phenotypes.
Snake venom systems have recently emerged as a powerful model system in which to investigate the evolution of gene regulatory architecture. More than 20 unique gene families have been independently recruited to produce venom components in the snake venom gland, and venom phenotypes vary substantially both within and between species. This system thus enables powerful comparative genomic and experimental interrogation of gene regulatory architecture structure and its role in adaptation.
Recently, I generated an integrative suite of functional genomics data to investigate the regulatory landscape of venom in the Prairie Rattlesnake (Crotalus viridis; Perry et al. 2022, Genome Res). This study identified novel regulatory sequences targeting venom genes, revealed features of chromatin regulation and interaction underlying tissue-specific gene expression in the venom gland, and found evidence supporting the co-option of broadly conserved transcription factors and signaling cascades to coordinate gene regulation in the venom gland. I am currently building upon this work by investigating variation in venom gene regulatory architecture across species, and testing hypotheses about how variation in gene regulation may underly intraspecific venom variation in natural populations.
In addition to this work, I have led or contributed to numerous studies on venom evolution and ecology, including investigations of venom gland physiology (Perry et al. 2020, Sci Rep), signatures of selection on venom genes (Schield et al. 2022, Nat Eco Evol), drivers of venom variation in natural populations (Smith et al. 2023, BMC Biol), coevolution between venomous snakes and venom-resistant mammalian prey (Pomento and Perry et al. 2016, Toxicon), and more.
Mechanisms, regulation, and evolution of hibernation in bears
Changes to existing regulatory architecture can “re-wire” gene regulatory networks to produce novel phenotypes. Because of the modularity and complexity of gene regulation, these changes may alter gene expression and signaling activity only in particular biological contexts (i.e., in a particular tissue or cell type). Understanding how regulatory networks are evolutionarily modified to produce novelty in certain contexts, while preserving their conserved and critical functions in other contexts, is therefore key to understanding the evolution of complex, expression-driven traits.
Hibernation in bears is a complex physiological adaptation characterized by the annual reduction of metabolic rate, body temperature, activity, and feeding during resource-scarce winter months. Previous studies have shown that these physiological shifts are associated with differential expression of thousands of genes across key metabolic tissues such as adipose, with many of these genes involved in major vertebrate signaling pathways such as insulin and AMPK signaling (Jansen et al. 2019). Hibernation capacity is also variable across bear lineages, such that species with year-round access to resources do not hibernate. Using this system, I am investigating the roles of gene regulatory network re-wiring in the evolution of hibernation physiology and how regulatory sequence evolution can drive the gain, loss, and modification of complex phenotypes.
I was awarded an NSF Office of Polar Programs Postdoctoral Research Fellowship in 2021 to investigate the roles of regulatory sequence evolution in adaptation of polar bears (Ursus maritimus) to the Arctic. Polar bears exhibit highly reduced hibernation capacity despite having diverged from brown bears only ~500,000 years ago. Given the gene regulatory complexity of hibernation, evolution of regulatory sequences may have played a particularly important role in the rapid adaptation of polar bears to the unique challenges of an Arctic environment. Through the integration of functional and comparative genomic approaches, this work characterized the regulatory landscape of hibernation in brown bears and identified regulatory regions that have undergone rapid evolution in the polar bear lineage. Many of these regulatory regions are predicted to target genes with important roles in metabolism, suggesting that regulatory evolution likely played a key role in physiological and metabolic specialization of polar bears to the Arctic. Findings from this work will be published in the near future!
In addition to this project, I have led or contributed to multiple recent studies investigating the role of gene regulation in hibernation, including investigations of differential isoform usage (Perry et al. 2022, ICB), regulatory serum proteins (Saxton and Perry et al. 2022, iScience), circadian rhythms (Vincent et al. 2023, J Comp Physiol B), and the effects of mid-hibernation feeding on gene expression and metabolic signaling pathways (Perry et al. 2023, Physiol Genomics). We also recently published an improved genome assembly for the brown bear, providing an excellent foundation for continued research into hibernation gene regulation (Armstrong et al. 2022, GBE).
Three-dimensional chromatin organization and interaction
The three-dimensional organization and interaction (i.e., 3D architecture) of the genome plays crucial roles in gene regulation and genome function. Using functional genomics approaches such as Hi-C sequencing, we can capture high-resolution information about this 3D architecture in the context of cell types, tissues, and/or phenotypes of interest. In addition to understanding how features of 3D organization and interaction contribute to the broader regulatory architecture of traits of interest, I am also interested in how variation in 3D architecture may contribute to phenotypic variation in natural populations. I am currently exploring questions related to the evolution and function of 3D architecture in both the snake venom and bear hibernation systems.
Previously, I have led or contributed to studies investigating the 3D architecture of snake venom gene regulation, including analyses of topologically associating domains (TADs) associated with venom gene arrays (Schield et al. 2019, Genome Res) and enhancer-gene interactions and chromatin loops involved in the regulation of specific venom genes in the Prairie Rattlesnake (Perry et al. 2022, Genome Res). Additionally, I led a comparative study of the 3D architecture of microchromosomes, small gene-rich chromosomes present in many non-mammalian vertebrate species (Perry et al. 2020, MBE). This work revealed conserved and previously under appreciated features of microchromosome biology, including high degrees of interchromosomal interaction, enrichment of open chromatin, and the co-localization of microchromosomes in a shared nuclear domain. I am currently investigating whether these unique features of microchromosome biology impact the function, regulation, and evolution of genes that they house, including several large, medically-relevant venom gene families.
