Publication Date:
2012-06-30
Description:
Background: As a model organism in biomedicine, the rhesus macaque (Macaca mulatta) is the mostwidely used nonhuman primate. Although a draft genome sequence was completed in 2007,there has been no systematic genome-wide comparison of genetic variation of this species tohumans. Comparative analysis of functional and nonfunctional diversity in this highlyabundant and adaptable non-human primate could inform its use as a model for humanbiology, and could reveal how variation in population history and size alters patterns andlevels of sequence variation in primates. Results: We sequenced the mRNA transcriptome and H3K4me3-marked DNA regions inhippocampus from 14 humans and 14 rhesus macaques. Using equivalent methodology andsampling spaces, we identified 462,802 macaque SNPs, most of which were novel anddisproportionately located in the functionally important genomic regions we had targeted inthe sequencing. At least one SNP was identified in each of 16,797 annotated macaque genes.Accuracy of macaque SNP identification was conservatively estimated to be 〉90%.Comparative analyses using SNPs equivalently identified in the two species revealed thatrhesus macaque has approximately three times higher SNP density and average nucleotidediversity as compared to the human. Based on this level of diversity, the effective populationsize of the rhesus macaque is approximately 80,000 which contrasts with an effectivepopulation size of less than 10,000 for humans. Across five categories of genomic regions,intergenic regions had the highest SNP density and average nucleotide diversity and CDS(coding sequences) the lowest, in both humans and macaques. Although there are morecoding SNPs (cSNPs) per individual in macaques than in humans, the ratio of dN/dS issignificantly lower in the macaque. Furthermore, the number of damaging nonsynonymouscSNPs (have damaging effects on protein functions from PolyPhen-2 prediction) in themacaque is more closely equivalent to that of the human. Conclusions: This large panel of newly identified macaque SNPs enriched for functionally significantregions considerably expands our knowledge of genetic variation in the rhesus macaque.Comparative analysis reveals that this widespread, highly adaptable species is approximatelythree times as diverse as the human but more closely equivalent in damaging variation.
Electronic ISSN:
1471-2156
Topics:
Biology
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