title: 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.
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, Center for Bioinformatics, School of Life Sciences & Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.|Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
authors.forename: Yuange
authors.initials: Y
authors.lastname: Duan
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, Center for Bioinformatics, School of Life Sciences & Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
authors.forename: Shengqian
authors.initials: S
authors.lastname: Dou
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, Center for Bioinformatics, School of Life Sciences & Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
authors.forename: Shiqi
authors.initials: S
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, Center for Bioinformatics, School of Life Sciences & Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, Center for Bioinformatics, School of Life Sciences & Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
authors.forename: Jian
authors.identifier: 0000-0002-4409-1667
authors.initials: J
authors.lastname: Lu
mesh_terms: D000241:Adenosine / Q000737:chemistry*; D000818:Animals; D017124:Conserved Sequence / Q000235:genetics; D004330:Drosophila / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D020869:Gene Expression Profiling; D049750:Genome, Insect; D007288:Inosine / Q000737:chemistry*; D008297:Male; D009154:Mutation; D009711:Nucleotides / Q000235:genetics; D017510:Protein Folding; D012313:RNA / Q000235:genetics; D017393:RNA Editing; D013045:Species Specificity; D009435:Synaptic Transmission; D013696:Temperature
chemical_list: D009711:Nucleotides; D007288:Inosine; D012313:RNA; D000241:Adenosine