Mitogenomic analysis of Chinese snub-nosed monkeys: Evidence of positive selection in NADH dehydrogenase genes in high-altitude adaptation

Chinese snub-nosed monkeys belong to the genus Rhinopithecus and are limited in distribution to six isolated mountainous areas in the temperate regions of Central and Southwest China. Compared to the other members of the subfamily Colobinae (or leaf-eating monkeys), these endangered primates are unique in being adapted to a high altitude environment and display a remarkable ability to tolerate low temperatures and hypoxia. They thus offer an interesting organismal model of adaptation to extreme environmental stress. Mitochondria generate energy by oxidative phosphorylation (OXPHOS) and play important roles in oxygen usage and energy metabolism. We analyzed the mitochondrial genomes of two Chinese snub-nosed monkey species and eight other colobines in the first attempt to understand the genetic basis of high altitude adaptation in non-human primates. We found significant evidence of positive selection in one Chinese snub-nosed monkey, Rhinopithecus roxellana, which is suggestive of adaptive change related to high altitude and cold weather stress. In addition, our study identified two potentially important adaptive amino acid residues (533 and 3307) in the NADH2 and NADH6 genes, respectively. Surprisingly, no evidence for positive selection was found in Rhinopithecus bieti (the other Chinese snub-nosed monkey analyzed). This finding is intriguing, especially considering that R. bieti inhabits a higher altitudinal distribution than R. roxellana. We hypothesize that a different adaptive genetic basis to high altitude survival exists in R. bieti from those seen in other mammals, and that positive selection and functionally associated mutations in this species may be detected in nuclear genes related to energy and oxygen metabolism. More information on the structure, function, and evolution of mitochondrial and nuclear genomes in Chinese snub-nosed monkeys is required to reveal the molecular mechanisms that underlie adaptations to high altitude survival in non-human primates.