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

作者：Yoav Shoshan, Noa Liscovitch‐Brauer, Joshua J. C. Rosenthal, Eli Eisenberg · 发表于：Molecular Biology and Evolution · 年份：2021 · DOI：10.1093/molbev/msab154 · 被引用次数：52 · 研究领域：RNA regulation and disease、RNA and protein synthesis mechanisms、CRISPR and Genetic Engineering

RNA editing by the ADAR enzymes converts selected adenosines into inosines, biological mimics for guanosines. By doing so, it alters protein-coding sequences, resulting in novel protein products that diversify the proteome beyond its genomic blueprint. Recoding is exceptionally abundant in the neural tissues of coleoid cephalopods (octopuses, squids, and cuttlefishes), with an over-representation of nonsynonymous edits suggesting positive selection. However, the extent to which proteome diversification by recoding provides an adaptive advantage is not known. It was recently suggested that the role of evolutionarily conserved edits is to compensate for harmful genomic substitutions, and that there is no added value in having an editable codon as compared with a restoration of the preferred genomic allele. Here, we show that this hypothesis fails to explain the evolutionary dynamics of recoding sites in coleoids. Instead, our results indicate that a large fraction of the shared, strongly recoded, sites in coleoids have been selected for proteome diversification, meaning that the fitness of an editable A is higher than an uneditable A or a genomically encoded G.