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

Abstract

High-elevation environments have lower atmospheric oxygen content, reduced temperatures, and higher levels of UV radiation than found at lower elevations. As such, species living at high elevations must overcome these challenges to survive, grow, and reproduce. American pikas (Ochotona princeps) are alpine lagomorphs that are habitat specialists typically found at elevations >2,000 m. 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 chromosomal reference genome assembly for the American pika relative to 8 other mammalian species targeted based on phylogenetic relatedness and (dis)similarity in ecology. 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; among these, we found 141 enriched terms with many related to hypoxia, metabolism, mitochondrial function/development, and DNA repair. We identified 15 significantly expanded gene families within the American pika across all orthologous gene groups that displayed functionally enriched terms associated with hypoxia adaptation. We further detected 196 positively selected genes, 41 of which have been associated with putative adaptation to hypoxia, cold tolerance, and response to UV following a literature review. In particular, OXNAD1, NRDC, and those genes critical in DNA repair represent important targets for future research to examine their functional implications in the American pika, especially as they may relate to adaptation to rapidly changing environments.

Keywords: Lagomorpha; UV radiation; cold tolerance; comparative genomics; hypoxia; local adaptation.

Fig. 1.

Significantly enriched GO terms for “pika-specific” genes in the American pika genome. Significantly enriched terms were identified using a hypergeometric test using BiNGO v3.0.4 (Maere et al. 2005) as implemented in Cytoscape v3.8.2 (Smoot et al. 2011). Semantically similar terms were grouped together using GO-Figure! v1.0.1 (Reijnders and Waterhouse 2021). Bolded terms were putatively associated with high-elevation adaptation. BP, biological process; MF, molecular function; CC, cellular component. GO IDs and grouped terms can be found in Supplementary Table 4.

Fig. 2.

Divergence time estimates and significantly expanded/contracted gene families across 9 mammalian species. Divergence times were estimated under a relaxed clock model as implemented in the MCMCTREE program of PAML v4.9 (Yang 2007). Branch labels indicate significantly expanded (+ values) and contracted (- values) gene families and were detected using CAFE v2.0 (Hahn et al. 2005, 2007; De Bie et al. 2006).