Comparative genomics reveals putative evidence for high elevation adaptation in the American pika genome (Ochotona princeps)

Background/Question/Methods

: High elevation environments (HEE) have lower atmospheric oxygen content, reduced temperatures, and higher levels of UV radiation than lower elevation environments. As such, species living in HEE must overcome these challenges to survive. American pikas (Ochotona princeps) are alpine lagomorphs that are habitat specialists typically found at elevations >2000m. Previous research has shown putative evidence for high elevation adaptation, however, investigations to date have been limited to a fraction of the genome. Here, we took a comparative genomics approach to identify putative regions under selection using a new chromosomal reference genome assembly for the American pika (OchPri4.0; NCBI Accession: GCF_014633375.1) relative to eight other mammalian species targeted based on phylogenetic affinity and ecological (dis)similarity. We first identified orthologous gene groups across species and then extracted groups containing only American pika genes as well as unclustered pika genes to inform functional enrichment analyses. We identified significantly expanded gene families within the American pika across all orthologous gene groups, as well as detected positively-selected genes (PSGs) among single-copy orthologs. We conducted a literature search for significantly enriched gene ontology (GO) terms, expanded gene families, and PSGs to find those with putative links to adaption to hypoxia, cold temperatures, UV exposure, or HEE.

Results/Conclusions

: We generated a chromosome-level reference genome assembly for American pika which offered significant improvements in contiguity and annotation quality over the previous assembly. Using this new resource, we found 25 pika-specific groups and 881 unclustered pika genes significantly enriched in 157 GO terms; of these, 35 terms had putative links to HEE related to metabolism, mitochondrial structure/function, and DNA repair. We found 15 significantly expanded gene families with functions related to immune response, transcription/translation, cell proliferation, catalytic activity, olfactory/pheromone receptor activity, oxidoreductase activity, and nuclear structure; these genes were enriched in 18 GO terms with several related to adaptation to cold and hypoxic environments. We further detected 196 PSGs and identified 41 genes with putative adaptive links to HEE. For example, NRDC has been shown to be critical for thermogenesis and homeostasis in mammals. Additionally, TREH is linked to cold adaption in numerous species. RIPOR2 has been shown to be an essential component for DNA repair following UV damage. These genes could be targets of future research to examine their functional implications in the American pika to expand our knowledge of how mammalian species adapt to rapidly changing environments on a genomic scale.