Whole-genome sequencing and analysis of the Malaysian cynomolgus macaque (Macaca fascicularis) genome

We identified approximately 9.7 million single nucleotide variants (SNVs) between the Malaysian cynomolgus and the Indian rhesus macaque genomes. Compared with humans, a smaller nonsynonymous/synonymous SNV ratio in the cynomolgus macaque suggests more effective removal of slightly deleterious mutations. Comparison of two cynomolgus (Malaysian and Vietnamese) and two rhesus (Indian and Chinese) macaque genomes, including previously published macaque genomes, suggests that Indochinese cynomolgus macaques have been more affected by gene introgression from rhesus macaques. We further identified 60 nonsynonymous SNVs that completely differentiated the cynomolgus and rhesus macaque genomes, and that could be important candidate variants for determining species-specific responses to drugs and pathogens. The demographic inference using the genome sequence data revealed that Malaysian cynomolgus macaques have experienced at least three population bottlenecks.This list of whole-genome SNVs will be useful for many future applications, such as an array-based genotyping system for macaque individuals. High-quality whole-genome sequencing of the cynomolgus macaque genome may aid studies on finding genetic differences that are responsible for phenotypic diversity in macaques and may help control genetic backgrounds among individuals.Cynomolgus macaque (Macaca fascicularis) is one of the most commonly used nonhuman primates in biomedical research worldwide [1]. It is also called the crab-eating or long-tailed macaque and belongs to the fascicularis group of the genus Macaca [2]. A number of pharmaceutical companies use cynomolgus macaques for drug development and, thus, identifying genetic components that contribute to their drug metabolism is a key issue in biomedical genomic research [3,4].Rhesus macaque (Macaca mulatta), whose draft genome sequence was determined by the Sanger sequencing method with a BAC clone assembly [5], is genetically closely related to the cynomolgus maca