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

Abstract

BackgroundThe genetic background of the cynomolgus macaque (Macaca fascicularis) is made complex by the high genetic diversity, population structure, and gene introgression from the closely related rhesus macaque (Macaca mulatta). Herein we report the whole-genome sequence of a Malaysian cynomolgus macaque male with more than 40-fold coverage, which was determined using a resequencing method based on the Indian rhesus macaque genome.ResultsWe 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.ConclusionsThis 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.

MicroRNA profling in ethylene glycol monomethyl ether-induced monkey testicular toxicity model

“…Since little is known regarding the existence of these pathways in cynomolgus monkeys, further investigation is needed to clarify the pathways by mRNA analysis and/or protein analysis. Cynomolgus monkey has been known to show genomic diversity dependent on its origin (Kawamoto et al, 2008;Higashino et al, 2012). Although the diversity of miR-NA sequence in cynomolgus monkeys might be pointed out, no obvious differences in miRNA profile were noted between Indonesian and Chinese origins in the present study.…”

“…Distilled water as a vehicle control or the EGME solution (300 mg/kg) at a volume of 5 mL/kg was administered orally to 3 males each for 4 consecutive days. To minimize the genetic diversity related to the different origin (Kawamoto et al, 2008;Higashino et al, 2012), monkeys from both Indonesian and Chinese origins were assigned to each group. The first day of the dosing period was designated as day 1.…”

The population genomics of rhesus macaques (Macaca mulatta) based on whole-genome sequences

“…We used default parameters, except for the option for "pattern." The pattern "6 +29 * 2" previously used for inferring cynomolgus macaque demographic history (Higashino et al 2012) and the pattern "4+25 * 2+4 +6" previously used for inferring great apes demographic histories (Prado-Martinez et al 2013) were used in this study. Due to technical reasons, PSMC was not able to infer the demographic history for one IRh (36461).The final historical reconstructions from the stairway plot analyses based on 75 high-coverage (>25×, average 38.1×) IRh and six high-coverage (>20×, average 34.4×) CRh were used as "Stairway plot -Indian rhesus" and "Stairway plot -Chinese rhesus," respectively.…”

Evolutionary History and Genetic Variation of Macaca mulatta and Macaca fascicularis

“…The genomes of Malaysian [46] and Mauritian [47] cynomolgus macaques have also been sequenced. A total of 2.1 million SNPs and 17,387 orthologs of human genes were identified in the Mauritian cynomolgus macaque genome [46].…”