Macaques are the most widely distributed non-human 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. Based on mapping to the rhesus macaque genome, we identified approximately 11.9 million single nucleotide variants (SNVs), 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 non-synonymous variants (TSHNVs), which were scored as deleterious in human by both PolyPhen-2 and SIFT, 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). PCR re-sequencing 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 million years ago, 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.

Cite: Zhenxin Fan, Guang Zhao, Peng Li, Naoki Osada, Jinchuan Xing, Yong Yi, Lianming Du, Pedro Silva, Hongxing Wang, RyuichiSakate, Xiuyue Zhang, Huailiang Xu, Bisong Yue, Jing Li (2014) Whole genome sequencing of Tibetan macaque (Macaca thibetana) provides new insight into the macaque evolutionary history. Molecular Biology and Evolution. 31 (6) : 1475–1489.

期刊杂志: Molecular Biology and Evolution

影响因子: 14.308

DOI: 10.1093/molbev/msu104