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[Preprint]. 2024 Apr 8:2024.04.07.588379. [Version 1] doi: 10.1101/2024.04.07.588379

Comparative genomics of macaques and integrated insights into genetic variation and population history

Shilong Zhang, Ning Xu, Lianting Fu, Xiangyu Yang, Yamei Li, Zikun Yang, Yu Feng, Kaiyue Ma, Xinrui Jiang, Junmin Han, Ruixing Hu, Lu Zhang, Luciana de Gennaro, Fedor Ryabov, Dan Meng, Yaoxi He, Dongya Wu, Chentao Yang, Annalisa Paparella, Yuxiang Mao, Xinyan Bian, Yong Lu, Francesca Antonacci, Mario Ventura, Valery A Shepelev, Karen H Miga, Ivan A Alexandrov, Glennis A Logsdon, Adam M Phillippy, Bing Su, Guojie Zhang, Evan E Eichler, Qing Lu, Yongyong Shi, Qiang Sun, Yafei Mao
PMCID: PMC11030432  PMID: 38645259

ABSTRACT

The crab-eating macaques ( Macaca fascicularis ) and rhesus macaques ( M. mulatta ) are widely studied nonhuman primates in biomedical and evolutionary research. Despite their significance, the current understanding of the complex genomic structure in macaques and the differences between species requires substantial improvement. Here, we present a complete genome assembly of a crab-eating macaque and 20 haplotype-resolved macaque assemblies to investigate the complex regions and major genomic differences between species. Segmental duplication in macaques is ∼42% lower, while centromeres are ∼3.7 times longer than those in humans. The characterization of ∼2 Mbp fixed genetic variants and ∼240 Mbp complex loci highlights potential associations with metabolic differences between the two macaque species (e.g., CYP2C76 and EHBP1L1 ). Additionally, hundreds of alternative splicing differences show post-transcriptional regulation divergence between these two species (e.g., PNPO ). We also characterize 91 large-scale genomic differences between macaques and humans at a single-base-pair resolution and highlight their impact on gene regulation in primate evolution (e.g., FOLH1 and PIEZO2 ). Finally, population genetics recapitulates macaque speciation and selective sweeps, highlighting potential genetic basis of reproduction and tail phenotype differences (e.g., STAB1 , SEMA3F , and HOXD13 ). In summary, the integrated analysis of genetic variation and population genetics in macaques greatly enhances our comprehension of lineage-specific phenotypes, adaptation, and primate evolution, thereby improving their biomedical applications in human diseases.

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