Adaptive evolution at mRNA editing sites in soft-bodied cephalopods

Abstract

Background The bulk of variability in mRNA sequence arises due to mutation—change in DNA sequence which is heritable if it occurs in the germline. However, variation in mRNA can also be achieved by post-transcriptional modification including mRNA editing, changes in mRNA nucleotide sequence that mimic the effect of mutations. Such modifications are not inherited directly; however, as the processes affecting them are encoded in the genome, they have a heritable component, and therefore can be shaped by selection. In soft-bodied cephalopods, adenine-to-inosine RNA editing is very frequent, and much of it occurs at nonsynonymous sites, affecting the sequence of the encoded protein. Methods We study selection regimes at coleoid A-to-I editing sites, estimate the prevalence of positive selection, and analyze interdependencies between the editing level and contextual characteristics of editing site. Results Here, we show that mRNA editing of individual nonsynonymous sites in cephalopods originates in evolution through substitutions at regions adjacent to these sites. As such substitutions mimic the effect of the substitution at the edited site itself, we hypothesize that they are favored by selection if the inosine is selectively advantageous to adenine at the edited position. Consistent with this hypothesis, we show that edited adenines are more frequently substituted with guanine, an informational analog of inosine, in the course of evolution than their unedited counterparts, and for heavily edited adenines, these transitions are favored by positive selection. Our study shows that coleoid editing sites may enhance adaptation, which, together with recent observations on Drosophila and human editing sites, points at a general role of RNA editing in the molecular evolution of metazoans.

Metapopulation of Ellobium Chinense Through The Late-Middle and Late Pleistocene Expansions: Four Covariate COI Hotspots Linked to G-Quadruplex Conformation

“…Such a strong unidirectional tendency can produce guanine richness under plausible positive selection pressure. For example, a positive selective bias from adenine-to-guanine transition has recently been characterized in soft-bodied cephalopods by Moldovan et al (2020) 23 . These authors suggested that edited adenines tend to be substituted to guanines, and this tendency is supported by positive selection at highly edited sites.…”

Characterization of metapopulation of Ellobium chinense through Pleistocene expansions and four covariate COI guanine-hotspots linked to G-quadruplex conformation

“…Such a strong unidirectional tendency can produce guanine richness under plausible positive selection pressure. For example, a positive selective bias from adenine-to-guanine transition has recently been characterized in soft-bodied cephalopods by Moldovan et al 24 . These authors suggested that edited adenines tend to be substituted to guanines, and this tendency is supported by positive selection at highly edited sites.…”

A hierarchy in clusters of cephalopod mRNA editing sites

“…Re-coding (non-synonymous) A-to-I editing in coleoids might be beneficial, as it diversifies the proteome and, consequently, allows for appropriate phenotypic and evolutionary responses to novel environments 13,14,22 . In line with this reasoning, we compared the fraction of re-coding sites among up-and downstream adenines in AA-clusters (Fig.…”

“…Editing in coleoids, involving up to 1% of all adenines in their transcriptomes, has been suggested to play an important role in proteome diversification, allowing for complex responses to the environment demonstrated by coleoids 13,14 . Along with that, editing sites could have an evolutionary value by rescuing deleterious G-to-A substitutions 38,39 or by enhancing the heritable trait variance needed for adaptation 22 .…”

“…As the coleoid editing sites demonstrate same contextual features and secondary RNA structure requirements as mammalian or Drosophila editing sites (Fig. 1bc) 13,22,25 , the answer to this question may enhance our understanding of the ADAR action and of the evolutionary and functional mechanisms involved in the emergence of new editing sites.…”