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.

Exome sequences of toque macaques (Macaca sinica) of Sri Lanka reveal many amino acid changes

“…Mauritian Fascicularis macaques were found to be genetically closer to the Vietnamese Fascicularis macaques. This result reconfirms findings by Osada et al (2015). M. thibetana M. sinica, M. arctoides, M. assemensis clustered together in the PCA signifying sinica group.…”

“…macaques (M. fascicularis), pig-tailed macaques (M. nemestrina) and Japanese macaques (M. fuscata) are also used. M. fascicularis of Mauritius Island are commonly used for research purpose, as they are genetically highly heterogeneous which make them valuable in testing responses to various drugs (Osada et al 2010;Yan et al 2011;Osada et al 2015). Fan et al 2014;Osada et al 2015;Fan et al 2018 also found that within individuals the proportion of heterozygous nonsynonymous polymorphisms are higher compared to synonymous polymorphisms in Mauritius M. fascicularis due to strong population bottle neck.…”

Genetic diversity in humans and non-human primates and its evolutionary consequences

“…The Indonesian-Malaysian population exhibits the highest genetic diversity among the fascicularis group of macaques (π = 3.2 × 10 −3 ) (Osada et al, 2010;Higashino et al, 2012;Fan et al, 2014). The cynomolgus macaque population on the island of Mauritius, which originated from the Indonesian-Malaysian population in the 16th century, shows about 20% less genetic diversity than the Indonesian-Malaysian population (Osada et al, 2015). Rhesus macaques (M. mulatta), a sister species of the cynomolgus macaques, are subdivided into Indian and Chinese populations, and exhibit slightly lower genetic diversity at the species level (π ≈ 2.0-2.9 × 10 −3 ) (Hernandez et al, 2007;Osada et al, 2010;Yan et al, 2011;Perry et al, 2012;Fan et al, 2014).…”

Mx1 and Mx2 key antiviral proteins are surprisingly lost in toothed whales

“…It is compelling to consider what events drove Mx loss in this clade of highly social marine mammals. Although other forces and scenarios cannot be ruled out (33), an intriguing hypothesis is that the loss enabled the survival of Odontoceti ancestors from a virus that took advantage of Mx function, possibly through direct interaction with the Mx proteins [e.g., human individuals and cells that inactivate the CCR5 gene are resistant to HIV-1 infection (34)], or through mimicry of the Mx proteins (35). Because herpes simplex virus 1 (HSV-1) has been shown to enhance infection by inducing an alternative splice variant of Mx1 omitting exons 10-12, and because alphaherpesviruses closely related to HSV-1 still infect dolphins today, an ancestor of HSV-1 is one possible candidate pathogen for this theory (2,3,36).…”