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

Copy number 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 1479 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 transcriptome data showed that nearly 46% of CNV genes were differentially expressed across populations and also mainly 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 qPCR, suggesting that these macaques may have different drug metabolism features. The CNV-dense regions, including fifteen first reported here, represent unstable genomic segments in macaques where biological innovation may evolve. Twelve gains and forty losses specific to the Barbary macaque contain genes with essential roles in energy homeostasis and immunity defence, inferring the genetic basis of its unique distribution in North Africa. Our study not only elucidated the genetic diversity across Macaca species from the perspective of structural variation, but 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.