Human-specific lncRNAs contributed critically to human evolution by distinctly regulating gene expression

Abstract

What genomic sequences make protein-coding genes generate divergent expression in closely related species, specifically, differentiate humans from apes, puzzle many researchers. Many studies examined species-specific gene birth, gene loss, and changes in promoters and transcription factor binding sites, but the identification and impact of human-specific lncRNAs remain unexplored. This study identified human-specific lncRNAs from GENCODE-annotated human lncRNAs, predicted their DNA binding sites (DBSs) genome-wide, and analyzed the DBSs and their counterparts in modern humans (CEU, CHB, and YRI), archaic humans (Altai Neanderthals, Denisovans, and Vindija Neanderthals), and chimpanzees. The results reveal how human-specific lncRNAs and their DBSs have transcriptionally regulated gene expression human-specifically. The rewiring of gene expression has undergone continuous evolution, significantly changed gene expression in the brain, promoted the adaptive evolution of humans, and influenced differences in modern humans. These results reveal the importance of human-specific lncRNAs (for human evolution) and highlight the importance of other species-specific lncRNAs.