Comparative genomic investigation of high-elevation adaptation in ectothermic snakes

Abstract

<p id="d1945241e464">Snakes of the genus <i>Thermophis</i> are endemic to the Tibetan plateau and occur at elevations over 3,500 m and present an opportunity to study the genetics mechanisms of adaptation to high-elevation conditions in ectotherms. Here, we provide a de novo genome of the Tibetan hot-spring snake, <i>Thermophis baileyi</i>, and conduct a series of comparisons with other reptiles. We identify genes under positive selection and test properties of allelic variants of proteins that are involved in DNA damage repair and responses to hypoxia. Functional assays reveal convergent genetic mechanisms that underlie high-elevation adaptation in both endotherms and ectotherms. </p><p class="first" id="d1945241e473">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>). </p>