Institute of Information Science Academia Sinica
講 題: TIGP (BIO)– A-to-I RNA editing: a possible explanation for the persistence of predicted damaging mutations in healthy individuals
講 者: 莊樹諄 博士 (中央研究院基因體研究中心)
時 間: 2019-10-17 (Thu) 14:00 – 16:00
地 點: 資訊所新館101演講廳
邀請人: TIGP- Bioinformatics Program

Adenosine-to-inosine (A-to-I) RNA editing is a very common co-/post-transcriptional modification that can lead to A-to-G changes at the RNA level and compensate for G-to-A genomic changes to a certain extent. It has been shown that each healthy individual can carry dozens of missense variants predicted to be severely deleterious. Why strongly detrimental variants are preserved in a population and not eliminated by negative natural selection remains mostly unclear. Here we ask if RNA editing correlates with the burden of deleterious A/G polymorphisms in a population. Integrating genome and transcriptome sequencing data from 447 human lymphoblastoid cell lines, we show that nonsynonymous editing activities (prevalence/level) are negatively correlated with the deleteriousness of A-to-G genomic changes and positively correlated with that of G-to-A genomic changes within the population. We find a significantly negative correlation between nonsynonymous editing activities and allele frequency of A within the population. This negative editing-allele frequency correlation is particularly strong when editing sites are located in highly important genes/loci. Examinations of deleterious missense variants from the 1000 Genomes Project further show a significantly higher proportion of rare missense mutations for G-to-A changes than for other types of changes. The proportion for G-to-A changes increases with increasing deleterious effects of the changes. Moreover, the deleteriousness of G-to-A changes is significantly positively correlated with the percentage of binding motif of editing enzymes at the variants. Overall, we show that nonsynonymous editing is associated with the increased burden of G-to-A missense mutations in healthy individuals, expanding RNA editing in pathogenomics studies.