Comparative genomic investigation of high-elevation adaptation in ectothermic snakes.

Abstract

Several previous genomic studies have focused on adaptation to high elevations, but these investigations have been largely limited to endotherms. Snakes of the genus <i>Thermophis</i> are endemic to the Tibetan plateau and therefore present an opportunity to study high-elevation adaptations in ectotherms. Here, we report the de novo assembly of the genome of a Tibetan hot-spring snake (<i>Thermophis baileyi</i>) and then compare its genome to the genomes of the other two species of <i>Thermophis</i>, as well as to the genomes of two related species of snakes that occur at lower elevations. We identify 308 putative genes that appear to be under positive selection in <i>Thermophis</i> We also identified genes with shared amino acid replacements in the high-elevation hot-spring snakes compared with snakes and lizards that live at low elevations, including the genes for proteins involved in DNA damage repair (<i>FEN1</i>) and response to hypoxia (<i>EPAS1</i>). Functional assays of the <i>FEN1</i> alleles reveal that the <i>Thermophis</i> allele is more stable under UV radiation than is the ancestral allele found in low-elevation lizards and snakes. Functional assays of <i>EPAS1</i> alleles suggest that the <i>Thermophis</i> protein has lower transactivation activity than the low-elevation forms. Our analysis identifies some convergent genetic mechanisms in high-elevation adaptation between endotherms (based on studies of mammals) and ectotherms (based on our studies of <i>Thermophis</i>).