Adaptive functions of structural variants in human brain development

• Published in: Science advances Vol. 10; no. 14; p. eadl4600
• Main Authors: Ding, Wanqiu, Li, Xiangshang, Zhang, Jie, Ji, Mingjun, Zhang, Mengling, Zhong, Xiaoming, Cao, Yong, Liu, Xiaoge, Li, Chunqiong, Xiao, Chunfu, Wang, Jiaxin, Li, Ting, Yu, Qing, Mo, Fan, Zhang, Boya, Qi, Jianhuan, Yang, Jie-Chun, Qi, Juntian, Tian, Lu, Xu, Xinwei, Peng, Qi, Zhou, Wei-Zhen, Liu, Zhijin, Fu, Aisi, Zhang, Xiuqin, Zhang, Jian-Jun, Sun, Yujie, Hu, Baoyang, An, Ni A, Zhang, Li, Li, Chuan-Yun
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 05-04-2024
• Subjects: Animals; Biomedicine and Life Sciences; Brain; Evolutionary Biology; Genetics; Genome; Genomics; Humans; Macaca mulatta; Research Resource; SciAdv r-resources
• ISSN: 2375-2548; 2375-2548
• DOI: 10.1126/sciadv.adl4600

Quantifying the structural variants (SVs) in nonhuman primates could provide a niche to clarify the genetic backgrounds underlying human-specific traits, but such resource is largely lacking. Here, we report an accurate SV map in a population of 562 rhesus macaques, verified by in-house benchmarks of eight macaque genomes with long-read sequencing and another one with genome assembly. This map indicates stronger selective constrains on inversions at regulatory regions, suggesting a strategy for prioritizing them with the most important functions. Accordingly, we identified 75 human-specific inversions and prioritized them. The top-ranked inversions have substantially shaped the human transcriptome, through their dual effects of reconfiguring the ancestral genomic architecture and introducing regional mutation hotspots at the inverted regions. As a proof of concept, we linked
, located on one of these inversions and down-regulated specifically in humans, to neuronal maturation and cognitive ability. We thus highlight inversions in shaping the human uniqueness in brain development.