A-to-I RNA editing alters less-conserved residues of highly conserved coding regions: Implications for dual functions in evolution

Abstract

The molecular mechanism and physiological function of recoding by A-to-I RNA editing is well known, but its evolutionary significance remains a mystery. We analyzed the RNA editing of the Kv2 K + channel from different insects spanning more than 300 million years of evolution: Drosophila melanogaster, Culex pipiens (Diptera), Pulex irritans (Siphonaptera), Bombyx mori (Lepidoptera), Tribolium castaneum (Coleoptera), Apis mellifera (Hymenoptera), Pediculus humanus (Phthiraptera), and Myzus persicae (Homoptera). RNA editing was detected across all Kv2 orthologs, representing the most highly conserved RNA editing event yet reported in invertebrates. Surprisingly, five of these editing sites were conserved in squid (Mollusca) and were possibly of independent origin, suggesting phylogenetic conservation of editing between mollusks and insects. Based on this result, we predicted and experimentally verified two novel A-to-I editing sites in squid synaptotagmin I transcript. In addition, comparative analysis indicated that RNA editing usually occurred within highly conserved coding regions, but mostly altered less-conserved coding positions of these regions. Moreover, more than half of these edited amino acids are genomically encoded in the orthologs of other species; an example of a conversion model of the nonconservative edited site is addressed. Therefore, these data imply that RNA editing might play dual roles in evolution by extending protein diversity and maintaining phylogenetic conservation.

Origins and evolution of ADAR‐mediated RNA editing

“…Comparative analysis indicated that A-to-I editing usually occurred in highly conserved coding regions, but usually recoded less-conserved coding positions of these regions (46,52). Our analyses indicate that edited sites accumulate mutations much more rapidly than unedited sites, and thus evolution of sites undergoing mRNA editing is accelerated to enhance protein diversity (46,52).…”

“…Thus, physiologically beneficial ADAR targets are fixed by purifying selection. A few examples about convergent evolution of ADAR targets supported this scenario (18,42,(45)(46). In addition to recoding, a few beneficial ADAR targets in noncoding RNA are fixed (Fig.…”

“…Our analyses indicate that edited sites accumulate mutations much more rapidly than unedited sites, and thus evolution of sites undergoing mRNA editing is accelerated to enhance protein diversity (46,52). Furthermore, more than half of these edited amino acids are genomically encoded in the orthologs of other species (46). Therefore, ADAR-mediated RNA editing not only extends the sequence diversity at the RNA and protein level, but also is a novel source of genetic variation at least in some genome sequence (52).…”

“…Our analyses indicate that edited sites accumulate mutations much more rapidly than unedited sites, and thus evolution of sites undergoing mRNA editing is accelerated to enhance protein diversity (46,52). Furthermore, more than half of these edited amino acids are genomically encoded in the orthologs of other species (46).…”

“…Fruit flies, mosquitoes, and butterflies have shared and species-specific syt I editing sites, while beetles, honeybees, and roaches do not edit syt I (41). Verification of these two A-to-I editing sites in squid indicates that RNA editing events might occur independently in insects and squid (46). These editing events occur independently in ion-channel families, suggesting that there is an adaptive benefit to regulate physiologically ion channels in this way.…”