Adaptation of A-to-I RNA editing in Drosophila

Abstract

Adenosine-to-inosine (A-to-I) editing is hypothesized to facilitate adaptive evolution by expanding proteomic diversity through an epigenetic approach. However, it is challenging to provide evidences to support this hypothesis at the whole editome level. In this study, we systematically characterized 2,114 A-to-I RNA editing sites in female and male brains of D. melanogaster, and nearly half of these sites had events evolutionarily conserved across Drosophila species. We detected strong signatures of positive selection on the nonsynonymous editing sites in Drosophila brains, and the beneficial editing sites were significantly enriched in genes related to chemical and electrical neurotransmission. The signal of adaptation was even more pronounced for the editing sites located in X chromosome or for those commonly observed across Drosophila species. We identified a set of gene candidates (termed “PSEB” genes) that had nonsynonymous editing events favored by natural selection. We presented evidence that editing preferentially increased mutation sequence space of evolutionarily conserved genes, which supported the adaptive evolution hypothesis of editing. We found prevalent nonsynonymous editing sites that were favored by natural selection in female and male adults from five strains of D. melanogaster. We showed that temperature played a more important role than gender effect in shaping the editing levels, although the effect of temperature is relatively weaker compared to that of species effect. We also explored the relevant factors that shape the selective patterns of the global editomes. Altogether we demonstrated that abundant nonsynonymous editing sites in Drosophila brains were adaptive and maintained by natural selection during evolution. Our results shed new light on the evolutionary principles and functional consequences of RNA editing.

The evolutionary arms race between transposable elements and piRNAs in Drosophila melanogaster

“…TE insertions often disrupt CDSs or regulatory sequences [31,40,46]. To explore the impact of TE insertions on the expression levels of the host genes, we examined the whole-body transcriptomes of adult females for 5 GDL strains (B12, I17, N10, T05, and ZW155) [114]. As expected [50,95,115], we found genes with novel TE insertions in exons, especially in CDSs, had significantly reduced expression levels ( Fig.…”

Regulation of gene expression and RNA editing in Drosophila adapting to divergent microclimates

“…The ECS is part of the core double-stranded RNA (dsRNA) region required for editing, and is the sequence opposite the editing sites in the secondary structure. We specifically identified how many sites have at least one highly differentiated SNP (top 0.5% Fst) within 100 bases, and how many have at least one differentiated SNP in their respective computationally predicted ECSs 14 , 31 . We found that 3/26 (11.5%) of differentially edited sites between the NFS1 and SFS fly lines are near at least one highly differentiated SNP, whereas 2/378 (5.3%) of non-differentially edited sites are near one ( p -value = 0.0022, one-sided Fisher’s exact test).…”

A-to-I RNA editing is developmentally regulated and generally adaptive for sexual reproduction in Neurospora crassa

“…In humans, A-to-I editing sites identified in the coding regions are largely deleterious rather than beneficial, as both the frequency and level of nonsynonymous editing events are significantly lower than those of synonymous editing events (11). Recently, it has been reported that the nonsynonymous editing sites in brains and evolutionarily constrained editing sites are generally adaptive in Drosophila (53)(54)(55). In this study, we showed that the nonsynonymous editing events in N. crassa are generally beneficial and favored by positive selection during evolution.…”