美国华盛顿大学Evan E. Eichler等研究人员合作揭示灵长类动物基因组的结构差异和反复突变区域。2024年2月29日，《细胞》杂志在线发表了这项成果。

研究人员利用多种长读测序技术对黑猩猩、倭黑猩猩、大猩猩、猩猩、长臂猿、猕猴、夜猴和狨猴的基因组进行了测序和组装。研究人员发现了1338997个谱系特异性固定结构变异（SV），破坏了1561个蛋白编码基因和136932个调控元件，其中包括最完整的人类特异性固定差异集。研究人员估计，在整个灵长类演化过程中，有819.47Mbp或27%的基因组受到SV的影响。

研究人员发现了1607个结构差异区域，在这些区域中，经常性的结构变异促成了SV热点的形成，在这些热点区域中，基因经常性地丢失（如CARD、C4和OLAH基因家族），同时又产生了更多的谱系特异性基因（如CKAP2、VPS36、ACBD7和NEK5旁系同源物），从而成为染色体快速多样化和正选择的目标（如RGPD基因家族）。高保真长读数测序使得这些动态的基因组区域，可以在灵长类物种内部和物种之间进行序列水平的分析。

附：英文原文

Title: Structurally divergent and recurrently mutated regions of primate genomes

Author: Yafei Mao, William T. Harvey, David Porubsky, Katherine M. Munson, Kendra Hoekzema, Alexandra P. Lewis, Peter A. Audano, Allison Rozanski, Xiangyu Yang, Shilong Zhang, DongAhn Yoo, David S. Gordon, Tyler Fair, Xiaoxi Wei, Glennis A. Logsdon, Marina Haukness, Philip C. Dishuck, Hyeonsoo Jeong, Ricardo del Rosario, Vanessa L. Bauer, Will T. Fattor, Gregory K. Wilkerson, Yuxiang Mao, Yongyong Shi, Qiang Sun, Qing Lu, Benedict Paten, Trygve E. Bakken, Alex A. Pollen, Guoping Feng, Sara L. Sawyer, Wesley C. Warren, Lucia Carbone, Evan E. Eichler

Issue&Volume: 2024-02-29

Abstract: We sequenced and assembled using multiple long-read sequencing technologies the genomes of chimpanzee, bonobo, gorilla, orangutan, gibbon, macaque, owl monkey, and marmoset. We identified 1,338,997 lineage-specific fixed structural variants (SVs) disrupting 1,561 protein-coding genes and 136,932 regulatory elements, including the most complete set of human-specific fixed differences. We estimate that 819.47 Mbp or ～27% of the genome has been affected by SVs across primate evolution. We identify 1,607 structurally divergent regions wherein recurrent structural variation contributes to creating SV hotspots where genes are recurrently lost (e.g., CARD, C4, and OLAH gene families) and additional lineage-specific genes are generated (e.g., CKAP2, VPS36, ACBD7, and NEK5 paralogs), becoming targets of rapid chromosomal diversification and positive selection (e.g., RGPD gene family). High-fidelity long-read sequencing has made these dynamic regions of the genome accessible for sequence-level analyses within and between primate species.

DOI: 10.1016/j.cell.2024.01.052

Source: https://www.cell.com/cell/fulltext/S0092-8674(24)00121-1