title: Hypoxia adaptations in the grey wolf (Canis lupus chanco) from Qinghai-Tibet Plateau.
abstract: The Tibetan grey wolf (Canis lupus chanco) occupies habitats on the Qinghai-Tibet Plateau, a high altitude (>3000 m) environment where low oxygen tension exerts unique selection pressure on individuals to adapt to hypoxic conditions. To identify genes involved in hypoxia adaptation, we generated complete genome sequences of nine Chinese wolves from high and low altitude populations at an average coverage of 25× coverage. We found that, beginning about 55,000 years ago, the highland Tibetan grey wolf suffered a more substantial population decline than lowland wolves. Positively selected hypoxia-related genes in highland wolves are enriched in the HIF signaling pathway (P = 1.57E-6), ATP binding (P = 5.62E-5), and response to an oxygen-containing compound (P≤5.30E-4). Of these positively selected hypoxia-related genes, three genes (EPAS1, ANGPT1, and RYR2) had at least one specific fixed non-synonymous SNP in highland wolves based on the nine genome data. Our re-sequencing studies on a large panel of individuals showed a frequency difference greater than 58% between highland and lowland wolves for these specific fixed non-synonymous SNPs and a high degree of LD surrounding the three genes, which imply strong selection. Past studies have shown that EPAS1 and ANGPT1 are important in the response to hypoxic stress, and RYR2 is involved in heart function. These three genes also exhibited significant signals of natural selection in high altitude human populations, which suggest similar evolutionary constraints on natural selection in wolves and humans of the Qinghai-Tibet Plateau.
authors: Sichuan Key Laboratory of Conservation Biology on Endangered Wildlife, Chengdu research base of giant panda breeding, Chengdu, Sichuan Province, P. R. China; Department of Ecology and Evolutionary Biology, UCLA, Los Angeles, California, United States of America.
authors: Wenping
authors: W
authors: Zhang
authors: Department of Ecology and Evolutionary Biology, UCLA, Los Angeles, California, United States of America; Key Laboratory of Bioresources and Ecoenvironment (Ministry of Education), College of Life Sciences, Sichuan University, Chengdu, People's Republic of China.
authors: Zhenxin
authors: Z
authors: Fan
authors: Department of Ecology and Evolutionary Biology, UCLA, Los Angeles, California, United States of America.
authors: Eunjung
authors: E
authors: Han
authors: Sichuan Key Laboratory of Conservation Biology on Endangered Wildlife, Chengdu research base of giant panda breeding, Chengdu, Sichuan Province, P. R. China.
authors: Rong
authors: R
authors: Hou
authors: Sichuan Key Laboratory of Conservation Biology on Endangered Wildlife, Chengdu research base of giant panda breeding, Chengdu, Sichuan Province, P. R. China.
authors: Liang
authors: L
authors: Zhang
authors: ISPRA, Ozzano dell'Emilia, Italy.
authors: Marco
authors: M
authors: Galaverni
authors: Sichuan Key Laboratory of Conservation Biology on Endangered Wildlife, College of Life Sciences, Sichuan University, Chengdu, P. R. China.
authors: Jie
authors: J
authors: Huang
authors: Sichuan Key Laboratory of Conservation Biology on Endangered Wildlife, Chengdu research base of giant panda breeding, Chengdu, Sichuan Province, P. R. China.
authors: Hong
authors: H
authors: Liu
authors: CIBIO-UP, University of Porto, Vairão, Portugal.
authors: Pedro
authors: P
authors: Silva
authors: Sichuan Key Laboratory of Conservation Biology on Endangered Wildlife, College of Life Sciences, Sichuan University, Chengdu, P. R. China.
authors: Peng
authors: P
authors: Li
authors: Department of Ecology and Evolutionary Biology, UCLA, Los Angeles, California, United States of America.
authors: John P
authors: JP
authors: Pollinger
authors: Sichuan Key Laboratory of Conservation Biology on Endangered Wildlife, College of Life Sciences, Sichuan University, Chengdu, P. R. China.
authors: Lianming
authors: L
authors: Du
authors: Key Laboratory of Bioresources and Ecoenvironment (Ministry of Education), College of Life Sciences, Sichuan University, Chengdu, People's Republic of China.
authors: XiuyYue
authors: X
authors: Zhang
authors: Key Laboratory of Bioresources and Ecoenvironment (Ministry of Education), College of Life Sciences, Sichuan University, Chengdu, People's Republic of China.
authors: Bisong
authors: B
authors: Yue
authors: Department of Ecology and Evolutionary Biology, UCLA, Los Angeles, California, United States of America.
authors: Robert K
authors: RK
authors: Wayne
authors: Sichuan Key Laboratory of Conservation Biology on Endangered Wildlife, Chengdu research base of giant panda breeding, Chengdu, Sichuan Province, P. R. China.
authors: Zhihe
authors: Z
authors: Zhang
mesh_terms: D000064:Acclimatization / Q000235:genetics; D000222:Adaptation, Physiological / Q000235:genetics*; D000531:Altitude; D000818:Animals; D005828:Genetics, Population; D006801:Humans; D000860:Hypoxia / Q000235:genetics*; D010101:Oxygen Consumption / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic / Q000235:genetics*; D018609:Tibet; D019596:Wolves / Q000235:genetics*