ADAR-Independent A-to-I RNA Editing is Generally Adaptive for Sexual Reproduction in Fungi

Abstract

ABSTRACTADAR-mediated A-to-I RNA editing is a well-known RNA modification mechanism in metazoans that can cause nonsynonymous changes leading to amino acid substitutions. Despite a few cases that are clearly functionally important, the biological significance of most nonsynonymous editing sites in animals remains largely unknown. Recently, genome-wide A-to-I editing was found to occur mainly in the coding regions and specifically during sexual reproduction in the wheat scab fungus Fusarium graminearum that lacks ADAR orthologs. In this study, we found that both the frequency and editing level of nonsynonymous editing is significantly higher than those of synonymous editing, suggesting that nonsynonymous editing is generally beneficial and under positive selection in F. graminearum. We also showed that nonsynonymous editing favorably targets functionally more important and more conserved genes, but at less-conserved sites, indicating that the RNA editing system is adapted to fine turn protein functions by avoiding potentially deleterious editing events. Furthermore, nonsynonymous editing in F. graminearum was found to be under codon-specific selection and most types of codon changes tend to cause amino acid substitutions with distinct physical-chemical properties and smaller molecular weights, which likely have more profound impact on protein structures and functions. In addition, we found that the most abundant synonymous editing of leucine codons is adapted to fine turn the protein expression by increasing codon usage bias. These results clearly show that A-to-I RNA editing in fungi is generally adaptive and recoding RNA editing may play an important role in sexual development in filamentous ascomycetes.