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Whole-genome sequencing of six Mauritian Cynomolgus macaques (Macaca fascicularis) reveals a genome-wide pattern of polymorphisms under extreme population bottleneck.

ABSTRACT: Cynomolgus macaques (Macaca fascicularis) were introduced to the island of Mauritius by humans around the 16th century. The unique demographic history of the Mauritian cynomolgus macaques provides the opportunity to not only examine the genetic background of well-established nonhuman primates for biomedical research but also understand the effect of an extreme population bottleneck on the pattern of polymorphisms in genomes. We sequenced the whole genomes of six Mauritian cynomolgus macaques and obtained an average of 20-fold coverage of the genome sequences for each individual. The overall level of nucleotide diversity was 23% smaller than that of the Malaysian cynomolgus macaques, and a reduction of low-frequency polymorphisms was observed. In addition, we also confirmed that the Mauritian cynomolgus macaques were genetically closer to a representative of the Malaysian population than to a representative of the Indochinese population. Excess of nonsynonymous polymorphisms in low frequency, which has been observed in many other species, was not very strong in the Mauritian samples, and the proportion of heterozygous nonsynonymous polymorphisms relative to synonymous polymorphisms is higher within individuals in Mauritian than Malaysian cynomolgus macaques. Those patterns indicate that the extreme population bottleneck made purifying selection overwhelmed by the power of genetic drift in the population. Finally, we estimated the number of founding individuals by using the genome-wide site frequency spectrum of the six samples. Assuming a simple demographic scenario with a single bottleneck followed by exponential growth, the estimated number of founders (∼20 individuals) is largely consistent with previous estimates.

SUBMITTER: Osada N

PROVIDER: S-EPMC5322541 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundMacaca fascicularis (cynomolgus or longtail macaques) is the most commonly used non-human primate in biomedical research. Little is known about the genomic variation in cynomolgus macaques or how the sequence variants compare to those of the well-studied related species, Macaca mulatta (rhesus macaque). Previously we identified single nucleotide polymorphisms (SNPs) in portions of 94 rhesus macaque genes and reported that Indian and Chinese rhesus had largely different SNPs. Here we identify SNPs from some of the same genomic regions of cynomolgus macaques (from Indochina, Indonesia, Mauritius and the Philippines) and compare them to the SNPs found in rhesus.ResultsWe sequenced a portion of 10 genes in 20 cynomolgus macaques. We identified 69 SNPs in these regions, compared with 71 SNPs found in the same genomic regions of 20 Indian and Chinese rhesus macaques. Thirty six (52%) of the M. fascicularis SNPs were overlapping in both species. The majority (70%) of the SNPs found in both Chinese and Indian rhesus macaque populations were also present in M. fascicularis. Of the SNPs previously found in a single rhesus population, 38% (Indian) and 44% (Chinese) were also identified in cynomolgus macaques. In an alternative approach, we genotyped 100 cynomolgus DNAs using a rhesus macaque SNP array representing 53 genes and found that 51% (29/57) of the rhesus SNPs were present in M. fascicularis. Comparisons of SNP profiles from cynomolgus macaques imported from breeding centers in China (where M. fascicularis are not native) showed they were similar to those from Indochina.ConclusionThis study demonstrates a surprisingly high conservation of SNPs between M. fascicularis and M. mulatta, suggesting that the relationship of these two species is closer than that suggested by morphological and mitochondrial DNA analysis alone. These findings indicate that SNP discovery efforts in either species will generate useful resources for both macaque species. Identification of SNPs that are unique to regional populations of cynomolgus macaques indicates that location-specific SNPs could be used to distinguish monkeys of uncertain origin. As an example, cynomolgus macaques obtained from 2 different breeding centers in China were shown to have Indochinese ancestry.

Dataset Information

Whole-genome sequencing of six Mauritian Cynomolgus macaques (Macaca fascicularis) reveals a genome-wide pattern of polymorphisms under extreme population bottleneck.

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