title: Whole-genome sequencing of tibetan macaque (Macaca Thibetana) provides new insight into the macaque evolutionary history.
abstract: Macaques are the most widely distributed nonhuman primates and used as animal models in biomedical research. The availability of full-genome sequences from them would be essential to both biomedical and primate evolutionary studies. Previous studies have reported whole-genome sequences from rhesus macaque (Macaca mulatta) and cynomolgus macaque (M. fascicularis, CE), both of which belong to the fascicularis group. Here, we present a 37-fold coverage genome sequence of the Tibetan macaque (M. thibetana; TM). TM is an endemic species to China belonging to the sinica group. On the basis of mapping to the rhesus macaque genome, we identified approximately 11.9 million single-nucleotide variants), of which 3.9 million were TM specific, as assessed by comparison two Chinese rhesus macaques (CR) and two CE genomes. Some genes carried TM-specific homozygous nonsynonymous variants (TSHNVs), which were scored as deleterious in human by both PolyPhen-2 and SIFT (Sorting Tolerant From Intolerant) and were enriched in the eye disease genes. In total, 273 immune response and disease-related genes carried at least one TSHNV. The heterozygosity rates of two CRs (0.002617 and 0.002612) and two CEs (0.003004 and 0.003179) were approximately three times higher than that of TM (0.000898). Polymerase chain reaction resequencing of 18 TM individuals showed that 29 TSHNVs exhibited high allele frequencies, thus confirming their low heterozygosity. Genome-wide genetic divergence analysis demonstrated that TM was more closely related to CR than to CE. We further detected unusual low divergence regions between TM and CR. In addition, after applying statistical criteria to detect putative introgression regions (PIRs) in the TM genome, up to 239,620 kb PIRs (8.84% of the genome) were identified. Given that TM and CR have overlapping geographical distributions, had the same refuge during the Middle Pleistocene, and show similar mating behaviors, it is highly likely that there was an ancient introgression event between them. Moreover, demographic inferences revealed that TM exhibited a similar demographic history as other macaques until 0.5 Ma, but then it maintained a lower effective population size until present time. Our study has provided new insight into the macaque evolutionary history, confirming hybridization events between macaque species groups based on genome-wide data.
authors.affiliation: Key Laboratory of Bioresources and Ecoenvironment (Ministry of Education), College of Life Sciences, Sichuan University, Chengdu, People's Republic of China ljtjf@126.com bsyue@scu.edu.cn.
authors.forename: Zhenxin
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Sichuan Key Laboratory of Conservation Biology on Endangered Wildlife, College of Life Sciences, Sichuan University, Chengdu, People's Republic of China ljtjf@126.com bsyue@scu.edu.cn.
authors.forename: Guang
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Bioresources and Ecoenvironment (Ministry of Education), College of Life Sciences, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Division of Evolutionary Genetics, Department of Population Genetics, National Institute of Genetics, Mishima, Shizuoka, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Osada
authors.affiliation: Department of Genetics, Rutgers, the State University of New Jersey.
authors.forename: Jinchuan
authors.initials: J
authors.lastname: Xing
authors.affiliation: Experimental Animal Institute of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yi
authors.affiliation: Key Laboratory of Bioresources and Ecoenvironment (Ministry of Education), College of Life Sciences, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Lianming
authors.initials: L
authors.lastname: Du
authors.affiliation: Research Center in Biodiversity and Genetic Resources, University of Porto (CIBIO-UP), Campus Agrário de Vairão, Vila do Conde, Portugal.
authors.forename: Pedro
authors.initials: P
authors.lastname: Silva
authors.affiliation: Experimental Animal Institute of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, People's Republic of China.
authors.forename: Hongxing
authors.initials: H
authors.lastname: Wang
authors.affiliation: Laboratory of Rare Disease Biospecimen, Department of Disease Bioresources Research, National Institute of Biomedical Innovation, Ibaraki, Osaka, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Sakate
authors.affiliation: Key Laboratory of Bioresources and Ecoenvironment (Ministry of Education), College of Life Sciences, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Xiuyue
authors.initials: X
authors.lastname: Zhang
authors.affiliation: College of Animal Science and Technology, Sichuan Agricultural University, Ya'an, People's Republic of China.
authors.forename: Huailiang
authors.initials: H
authors.lastname: Xu
authors.affiliation: Sichuan Key Laboratory of Conservation Biology on Endangered Wildlife, College of Life Sciences, Sichuan University, Chengdu, People's Republic of China ljtjf@126.com bsyue@scu.edu.cn.
authors.forename: Bisong
authors.initials: B
authors.lastname: Yue
authors.affiliation: Key Laboratory of Bioresources and Ecoenvironment (Ministry of Education), College of Life Sciences, Sichuan University, Chengdu, People's Republic of China ljtjf@126.com bsyue@scu.edu.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D004194:Disease / Q000235:genetics*; D019143:Evolution, Molecular; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D016678:Genome; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008251:Macaca / Q000145:classification* / Q000235:genetics*; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D013045:Species Specificity
keywords: SNVs; Tibetan macaque; demographic trajectories; genetic divergence; introgression; whole-genome sequencing