Adaptive functions of structural variants in human brain development.
Sci Adv
; 10(14): eadl4600, 2024 Apr 05.
Article
em En
| MEDLINE
| ID: mdl-38579006
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.
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Base de dados:
MEDLINE
Assunto principal:
Genoma
/
Genômica
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article