Abstract
Genome-wide studies on high-altitude adaptation have received increased attention as a classical case of organismal evolution under extreme environment. However, the current genetic understanding of high-altitude adaptation emanated mainly from autosomal analyses. Only a few earlier genomic studies paid attention to the allosome. In this study, we performed an intensive scan of the X chromosome of public genomic data generated from Tibetan Mastiff (TM) and five other dog populations for indications of high-altitude adaptation. We identified five genes showing signatures of selection on the X chromosome. Notable among these genes was angiomotin (AMOT), which is related to the process of angiogenesis. We sampled additional 11 dog populations (175 individuals in total) at continuous altitudes in China from 300 to 4,000 meters to validate and test the association between the haplotype frequency of AMOT gene and altitude adaptation. The results suggest that AMOT gene may be a notable candidate gene for the adaptation of TM to high-altitude hypoxic conditions. Our study shows that X chromosome deserves consideration in future studies of adaptive evolution.
Highlights
Adaptation to high-altitude environments, characterised by extreme conditions like hypoxia, low temperature, and high ultraviolet radiation, has been of great interest in evolutionary biology research[1,2,3,4,5,6]
Two positively selected genes (PSGs), i.e., EPAS1 and HBB, which are associated with hypoxia-inducible factor (HIF) pathway and oxygen transportation, and one PSG, i.e., PLXNA4, which functions in angiogenesis by interacting with VEGF41, have been reported as targeted candidate genes for adaptation to high-altitude[18]
In our current selective scans on X chromosome in Tibetan Mastiff (TM) and other dog populations from different elevation gradients, we have identified five new PSGs
Summary
Adaptation to high-altitude environments, characterised by extreme conditions like hypoxia, low temperature, and high ultraviolet radiation, has been of great interest in evolutionary biology research[1,2,3,4,5,6]. Numerous candidate genes which may be contributing to high-altitude adaptation, for instance those related to hypoxia (e.g., EPAS1, EGLN1, PPARA and HBB identified from human populations), energy metabolism (e.g., PKLR, ENO3 and DNAH9 identified from non-human highland animals) and DNA repair (e.g., BCL3, ERCC4 and ERCC6 identified from non-human highland animals), have been identified from studies of native highlanders with different time depths of exposure to high-altitude. By reanalysing publicly available genomic data from a TM population (10 individuals) and five other dog populations (50 individuals) from lower altitudes[17], we identified five genes showing signatures of selection (ALG13, AMOT, DCX, LHFPL1 and TRPC5) on the X chromosome of TM population. The results corroborated the initial findings that AMOT gene may be an important target for TM’s adaptation to hypoxic conditions at their high-altitude habitat
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