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De novo enhancer function in divergent hominin haplotypes

ABSTRACT: Identifying functional changes in gene regulatory elements in the human lineage is essential to understanding how humans emerged as a species. We performed genome-wide comparative genomic analysis of humans and great apes to identify 1581 Human Ancestor Quickly-Evolved Regions (HAQERs), which we identify as the fastest-evolved regions of the human genome (hg38). To detect how rapid sequence divergence contributed to divergent gene regulatory functionality in HAQERs, we designed in vivo STARR-seq as a multiplex single-cell assay of enhancer activity in the developing mouse brain. We tested multiple haplotypes from hominins (Human/Neanderthal/Denisova) and non-hominins (Chimpanzee and the inferred Human-Chimpanzee ancestor) for 13 HAQERs to assess their enhancer activity in the developing brain. We found significant differences in enhancer activity between hominins and non-hominins in 8 of these sequences.

ORGANISM(S): synthetic construct Mus musculus

PROVIDER: GSE212159 | GEO | 2022/11/23

REPOSITORIES: GEO

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