Evolution of transcript modification by N⁶-methyladenosine in primates

Phenotypic differences within populations and between closely related species are often driven by variation and evolution of gene expression. However, most analyses have focused on the effects of genomic variation at cis-regulatory elements such as promoters and enhancers that control transcriptional activity, and little is understood about the influence of post-transcriptional processes on transcript evolution. Post-transcriptional modification of RNA by N⁶-methyladenosine (m⁶A) has been shown to be widespread throughout the transcriptome, and this reversible mark can affect transcript stability and translation dynamics. Here we analyze m⁶A mRNA modifications in lymphoblastoid cell lines (LCLs) from human, chimpanzee and rhesus, and we identify patterns of m⁶A evolution among species. We find that m⁶A evolution occurs in parallel with evolution of consensus RNA sequence motifs known to be associated with the enzymatic complexes that regulate m⁶A dynamics, and expression evolution of m⁶A-modified genes occurs in parallel with m⁶A evolution.