A-to-I editing sites are a genomically encoded G: implications for the evolutionary significance and identification of novel editing sites.
Ribonucleic acid (RNA) editing can extend transcriptomic and proteomic diversity by changing the identity of a particular codon. Genetic recoding as a result of adenosine-to-inosine (A-to-I) RNA editing can alter highly conserved or invariant coding positions in proteins. Interestingly, examples exist in which A-to-I editing sites in one species are fixed genomically as a G in a closely related species. Phylogenetic analysis indicates that G-to-A mutations at the DNA level may be corrected by post-transcriptional A-to-I RNA editing, while in turn, the edited I (G) may be hardwired into the genome, resulting in an A-to-G mutation. We propose a model in which nuclear A-to-I RNA editing acts as an evolutionary intermediate of genetic variation. We not only provide information on the mechanism behind the evolutionary acquisition of an A-to-I RNA editing site but also demonstrate how to predict nuclear A-to-I editing sites by identifying positions where an RNA editing event would maintain the conservation of a protein relative to its homologs in other species. We identified a novel edited site in the fourth exon of the cacophony transcript coding calcium channel alpha1 and verified it experimentally.
Tian
Nan
N
Wu
Xiaojie
X
Zhang
Yaozhou
Y
Jin
Yongfeng
Y
D000225:Adenine / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019143:Evolution, Molecular; D005091:Exons; D014644:Genetic Variation; D016678:Genome / Q000235:genetics; D006151:Guanosine / Q000737:chemistry; D007288:Inosine / Q000737:chemistry; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D017393:RNA Editing / Q000235:genetics*; D011950:Receptors, Cholinergic / Q000235:genetics
D011950:Receptors, Cholinergic; D006151:Guanosine; D007288:Inosine; D000225:Adenine