Adaptive functions of structural variants in human brain development
Wanqiu Ding, Xiangshang Li, Jie Zhang, Jie Zhang, Mingjun Ji, Mengling Zhang, Xiaoming Zhong, Yong Cao, Xiaoge Liu, Chunqiong Li, Chunqiong Li, Chunfu Xiao, Jiaxin Wang, Ting Li, Qing Yu, Fan Mo, Boya Zhang, Jianhuan Qi, Jie-Chun Yang, Juntian Qi, Lu Tian, Xinwei Xu, Qi Peng, Wei‐Zhen Zhou, Zhijin Liu, Aisi Fu, Xiuqin Zhang, Jianjun Zhang, Jianjun Zhang, Yujie Sun, Baoyang Hu, Ni A. An, Li Zhang, Chuan‐Yun Li, Chuan‐Yun Li
Abstract
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 APCDD1 , 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.