Genomic copy number variation study of ninemacaca species provides new insights into their genetic divergence, adaptation, and biomedical application

Abstract

Copynumber variation (CNV) can promote phenotypic diversification and adaptive evolution.However, the genomic architecture of CNVs among Macaca species remains scarcely reported, and the roles of CNVs in adaptation and evolution of macaques have not been well addressed. Here, we identified and characterized 1,479 genome-wide hetero-specific CNVs across nine Macaca species with bioinformatic methods, along with 26 CNV-dense regions and dozens of lineage-specific CNVs. The genes intersecting CNVs were overrepresented in nutritional metabolism, xenobiotics/drug metabolism, and immune-related pathways. Population-level transcriptomedata showedthatnearly46%ofCNVgeneswere differentially expressedacrosspopulations andalsomainly consisted of metabolic and immune-related genes, which implied the role of CNVs in environmental adaptation of Macaca. Several CNVs overlapping drug metabolism genes were verified with genomic quantitative polymerase chain reaction, suggesting that these macaquesmayhave differentdrugmetabolism features.TheCNV-dense regions, including15first reportedhere, represent unstable genomic segments inmacaqueswhere biological innovationmay evolve. Twelvegains and 40 losses specific to theBarbarymacaque containgeneswithessential roles in energyhomeostasis andimmunitydefense, inferring the geneticbasis of its unique distributionin NorthAfrica.Our study not only elucidatedthe geneticdiversity acrossMacaca species fromthe perspectiveof structural variationbut also provided suggestive evidence for the role of CNVs in adaptation and genome evolution. Additionally, our findings provide new insights into the application of diverse macaques to drug study.