Genome-wide copy number variation drives adaptive evolution in Macaca mulatta Populations

Copy number variation (CNV) represents a significant contributor to intraspecific genomic diversity, yet remains undercharacterized in rhesus macaque (Macaca mulatta) populations. In this study, we performed whole-genome sequencing of eight M. m. lasiotis individuals and integrated these with six subspecies-representative genomes, yielding a comparative dataset of 60 rhesus macaque genomes. Utilizing a read-depth-based approach for CNV detection, our analysis identified approximately 59.6 Mb (2.2% of the reference genome) exhibiting copy number variation. We established a comprehensive CNV map consisting of 1272 non-overlapping CNV regions (CNVRs) across the M. mulatta genome. Hierarchical clustering analysis revealed discordance between CNVR-derived population structure and SNV-based phylogenetic relationships among Chinese subspecies. Comparative genomic analysis identified highly differentiated CNVRs between Indian and Chinese populations enriched for genes associated with immune response and xenobiotic metabolism. Subspecies-specific CNVRs (su_CNVRs) showed functional enrichment in pathways related to environmental adaptation and phenotypic variation. Notably, M. m. tcheliensis exhibited higher gene copies in METRNL and FBP1/FBP2 genes than other subspecies, potentially helping it adapt to cold environments and enhance gluconeogenesis capacity under food scarcity in the cold season. Furthermore, we identified six body size-associated genes with considerable copy number variation among different subspecies, highlighting CNV-mediated regulation of body size in M. mulatta subspecies. This investigation not only elucidates the evolutionary significance of CNVs in shaping genomic architecture and adaptive traits in M. mulatta, but also establishes a foundational resource for future population genetics studies utilizing structural variation markers.