Evolutionarily significant A-to-I RNA editing events originated through G-to-A mutations in primates

Abstract

BackgroundRecent studies have revealed thousands of A-to-I RNA editing events in primates, but the origination and general functions of these events are not well addressed.ResultsHere, we perform a comparative editome study in human and rhesus macaque and uncover a substantial proportion of macaque A-to-I editing sites that are genomically polymorphic in some animals or encoded as non-editable nucleotides in human. The occurrence of these recent gain and loss of RNA editing through DNA point mutation is significantly more prevalent than that expected for the nearby regions. Ancestral state analyses further demonstrate that an increase in recent gain of editing events contribute to the over-representation, with G-to-A mutation site as a favorable location for the origination of robust A-to-I editing events. Population genetics analyses of the focal editing sites further reveal that a portion of these young editing events are evolutionarily significant, indicating general functional relevance for at least a fraction of these sites.ConclusionsOverall, we report a list of A-to-I editing events that recently originated through G-to-A mutations in primates, representing a valuable resource to investigate the features and evolutionary significance of A-to-I editing events at the population and species levels. The unique subset of primate editome also illuminates the general functions of RNA editing by connecting it to particular gene regulatory processes, based on the characterized outcome of a gene regulatory level in different individuals or primate species with or without these editing events.Electronic supplementary materialThe online version of this article (10.1186/s13059-019-1638-y) contains supplementary material, which is available to authorized users.

Adaptive Proteome Diversification by Nonsynonymous A-to-I RNA Editing in Coleoid Cephalopods

“…The “harm-permitting” model is supported by a previous analysis of cephalopod recoding sites which showed an enrichment of recoding in restorative sites (sites for which the edited version of the transcript encodes for an ancestral version of the protein) ( Jiang and Zhang 2019 ), in accordance with prior studies in other species ( Tian et al 2008 ; Zhang et al 2014 ; An et al 2019 ). Further, it was suggested that “diversifying editing,” where recoding introduces an amino-acid that was not present ancestrally, is suppressed ( f N / f S < 1), indicating an overall deleterious effect.…”

Human A-to-I RNA editing SNP loci are enriched in GWAS signals for autoimmune diseases and under balancing selection

“…Several studies have found that editable A's are more likely to be replaced with G's during evolution [15,[48][49][50]. Some researchers think that this phenomenon suggests that A-to-I RNA editing serves as a safeguard and is beneficial because it reverses harmful G-to-A mutation in RNA transcripts; others argue that this observation suggests that A-to-I RNA editing is non-adaptive because G's are more acceptable at the editable A sites than un-editable A sites.…”

Potential of Transcript Editing Across Mitogenomes of Early Land Plants Shows Novel and Familiar Trends

“…RNA editing is a modification of transcripts encoded by organellar and nuclear genomes that occurs in various organisms, including animals, plants, fungi, and protists [1,2,3,4]. The modifications of transcripts caused by the RNA editing effect with encoding of alternative amino acid sequences is necessary for correct functioning of some protein-coding genes [5].…”