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

Abstract

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 non-synonymous 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 to a restoration of the preferred genomic allele. Here we show 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.

Genome and transcriptome mechanisms driving cephalopod evolution

“…While A-to-I mRNA editing occurs in other animals, it has been reported to be several orders of magnitude more prevalent in coleoid cephalopods 9 , 10 . Case studies of specific neuronal genes have argued that mRNA editing in cephalopods can be adaptive 7 , 9 , 53 , 54 , although editing is influenced by diverse evolutionary forces and non-adaptive explanations have also been proposed 55 . The frequency and tissue-specificity of coeloid mRNA editing are poorly characterized in part due to the lack of a complete, high-quality reference genome against which transcriptomes can be compared.…”

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 , 25 , 28 , 29 . In line with this reasoning coupled with the observation that downstream sites in AA-clusters were more prone to editing, we compared the fraction of sites with non-synonymous A-to-G substitutions among up- and downstream adenines in AA-clusters (Fig.…”

“…mammals and Drosophila 13 , 14 , 24 . Editing in coleoids involves up to 1% of all adenines in the transcriptomes and has been suggested to play an important role in proteome diversification, allowing for responses to many environmental cues, such as phenotypic adjustments to low temperatures 13 , 14 , 25 . Along with that, editing sites could have an evolutionary value by rescuing deleterious G-to-A substitutions 26 , 27 or by providing heritable phenotypes selection can act upon, thus enhancing the rate of adaptation 28 , 29 .…”

MicroRNAs are deeply linked to the emergence of the complex octopus brain

“…Because extensive editing is not abundant in other mollusks including Nautilus , a cephalopod and the living sister group of the coleoids with a simpler nervous system, this process has been hypothesized to drive the cognitive success of coleoids ( 9 ), perhaps by providing a mechanism to expand and regulate the coding repertoire of mRNAs. However, it is difficult to explain the evolution of complex heritable traits by the actions of a single trans-acting factor, and indeed it has been proposed that the editing phenomena in coleoids are mainly non-adaptive (( 11 ), but see ( 12 )). Because ADARs interact and regulate many classes of RNAs (for example, the silencing of transposon RNA ( 13 ), the biogenesis of circular RNAs (circRNAs) ( 14 ), and defense against viral RNAs ( 15 ), we hypothesized that post-transcriptional regulation of RNA in general is potentially linked to the evolution of the complex nervous system of the coleoid cephalopods.…”