title: The Landscape of A-to-I RNA Editome Is Shaped by Both Positive and Purifying Selection.
abstract: The hydrolytic deamination of adenosine to inosine (A-to-I editing) in precursor mRNA induces variable gene products at the post-transcription level. How and to what extent A-to-I RNA editing diversifies transcriptome is not fully characterized in the evolution, and very little is known about the selective constraints that drive the evolution of RNA editing events. Here we present a study on A-to-I RNA editing, by generating a global profile of A-to-I editing for a phylogeny of seven Drosophila species, a model system spanning an evolutionary timeframe of approximately 45 million years. Of totally 9281 editing events identified, 5150 (55.5%) are located in the coding sequences (CDS) of 2734 genes. Phylogenetic analysis places these genes into 1,526 homologous families, about 5% of total gene families in the fly lineages. Based on conservation of the editing sites, the editing events in CDS are categorized into three distinct types, representing events on singleton genes (type I), and events not conserved (type II) or conserved (type III) within multi-gene families. While both type I and II events are subject to purifying selection, notably type III events are positively selected, and highly enriched in the components and functions of the nervous system. The tissue profiles are documented for three editing types, and their critical roles are further implicated by their shifting patterns during holometabolous development and in post-mating response. In conclusion, three A-to-I RNA editing types are found to have distinct evolutionary dynamics. It appears that nervous system functions are mainly tested to determine if an A-to-I editing is beneficial for an organism. The coding plasticity enabled by A-to-I editing creates a new class of binary variations, which is a superior alternative to maintain heterozygosity of expressed genes in a diploid mating system.
authors.affiliation: Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yimeng
authors.initials: Y
authors.lastname: Kong
authors.affiliation: Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Bohu
authors.initials: B
authors.lastname: Pan
authors.affiliation: Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Longxian
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Physiology, Michigan State University, East Lansing, Michigan, United States of America.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Wang
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.|Shanghai Center for Bioinformation Technology, Shanghai Industrial Technology Institute, Shanghai, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Hao
authors.affiliation: Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Li
mesh_terms: D000241:Adenosine / Q000235:genetics; D000818:Animals; D017124:Conserved Sequence / Q000235:genetics; D004330:Drosophila / Q000235:genetics; D019143:Evolution, Molecular; D005091:Exons / Q000235:genetics; D007288:Inosine / Q000235:genetics; D010802:Phylogeny; D017393:RNA Editing / Q000235:genetics*; D012641:Selection, Genetic / Q000235:genetics*; D059467:Transcriptome / Q000235:genetics*
chemical_list: D007288:Inosine; D000241:Adenosine