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 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 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 quantitative polymerase chain reaction, suggesting that these macaques may have different drug metabolism features. The CNV-dense regions, including 15 first reported here, represent unstable genomic segments in macaques where biological innovation may evolve. Twelve gains and 40 losses specific to the Barbary macaque contain genes with essential roles in energy homeostasis and immunity defense, 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.

中文翻译：

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九种猕猴的基因组拷贝数变异研究为它们的遗传差异、适应性和生物医学应用提供了新的见解。

拷贝数变异 (CNV) 可以促进表型多样化和适应性进化。然而，猕猴物种中 CNV 的基因组结构仍然鲜有报道，而且 CNV 在猕猴适应和进化中的作用尚未得到很好的解决。在这里，我们鉴定并表征了 9 个猕猴中的1,479 个全基因组异种特异性 CNV。物种，以及 26 个 CNV 密集区域和数十个谱系特异性 CNV。与 CNV 相交的基因在营养代谢、异生物质/药物代谢和免疫相关通路中过多。种群水平转录组数据显示，近46%的CNV基因在种群间差异表达，并且主要由代谢和免疫相关基因组成，这暗示了CNVs在猕猴环境适应中的作用. 通过基因组定量聚合酶链反应验证了几个重叠药物代谢基因的CNV，表明这些猕猴可能具有不同的药物代谢特征。CNV 密集区域，包括此处首次报道的 15 个区域，代表了可能进化生物创新的猕猴不稳定的基因组片段。巴巴里猕猴特有的 12 项收益和 40 项损失包含在能量稳态和免疫防御中具有重要作用的基因，推断其在北非独特分布的遗传基础。我们的研究不仅阐明了猕猴的遗传多样性从结构变异的角度来看物种，但也为 CNV 在适应和基因组进化中的作用提供了暗示性证据。此外，我们的发现为不同猕猴在药物研究中的应用提供了新的见解。