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Whole-genome sequencing of six dog breeds from continuous altitudes reveals adaptation to high-altitude hypoxia  

2014-08-26 11:47:16|  分类: 文献学习 |  标签: |举报 |字号 订阅

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The hypoxic environment imposes severe selective pressure on species living at high altitude. To understand the genetic bases of adaptation to high altitude in dogs, we performed whole-genome sequencing of 60 dogs including five breeds living at continuous altitudes along the Tibetan Plateau from 800 to 5100 m as well as one European breed. More than 150× sequencing coverage for each breed provides us with a comprehensive assessment of the genetic polymorphisms of the dogs, including Tibetan Mastiffs. Comparison of the breeds from different altitudes reveals strong signals of population differentiation at the locus of hypoxia-related genes including endothelial Per-Arnt-Sim (PAS) domain protein 1 (EPAS1) and beta hemoglobin cluster. Notably, four novel nonsynonymous mutations specific to high-altitude dogs are identified at EPAS1, one of which occurred at a quite conserved site in the PAS domain. The association testing between EPAS1 genotypes and blood-related phenotypes on additional high-altitude dogs reveals that the homozygous mutation is associated with decreased blood flow resistance, which may help to improve hemorheologic fitness. Interestingly, EPAS1 was also identified as a selective target in Tibetan highlanders, though no amino acid changes were found. Thus, our results not only indicate parallel evolution of humans and dogs in adaptation to high-altitude hypoxia, but also provide a new opportunity to study the role of EPAS1 in the adaptive processes.
Whole-genome sequencing of six dog breeds from continuous altitudes reveals adaptation to high-altitude hypoxia - 喜欢吃桃子 - wangyufeng的博客
Figure 1. Genetic relationships and population structure of the 60 dogs based on all autosomal SNPs. (A) Principal component plot. The first (PC1) and second component (PC2) are shown in the main figure, while the third (PC3) and fourth component (PC4) are shown in the inset. The percentages indicate the proportion of variance explained by each component. (B) Unrooted neighbor-joining tree. The evolutionary distance is measured by the number of net nucleotide substitutions between individuals. (C ) Population structures with the number of ancestral clusters K from 2 to 6. Each color represents one ancestral cluster and each vertical bar represents one dog. The length of colored segments represents corresponding ancestry attributions
 
Genome Res. August 2014 24: 1308-1315; Published in Advance April 10, 2014, doi:10.1101/gr.171876.113
Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101
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