A single mutation underlying phenotypic convergence for hypoxia adaptation on the Qinghai-Tibetan Plateau

Similar highland phenotypes have evolved in different endemic mammals in
the Qinghai-Tibetan Plateau (QTP). However, until' now, we know
little about genomic underpinnings of these convergent phenotypes. Here,
we de novo sequenced genomes of plateau pika and plateau zokor. Along with
yak and Tibetan antelope genomes, we discovered that all four QTP mammal
species share a mutation Q247R in RETSAT. In vitro functional experiments
indicate that this mutation significantly increases RETSAT enzymatic
activity. Knock-in mice carrying this mutation can reproduce highland
traits featuring larger heart size and lower pulmonary artery pressure,
and importantly, survive longer under hypoxic conditions. Our findings
identify a novel gene involved in hypoxia adaptation and heart enlargement
and more importantly highlight that convergent highland phenotypes can be
determined by a single mutation.