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

16. CC-BY-ND 4.0 International license not peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was. ABSTRACT 17 18 ADAR-mediated A-to-I RNA editing is a well-known RNA modification mechanism in 19 metazoans that can cause nonsynonymous changes leading to amino acid substitutions. Despite 20 a few cases that are clearly functionally important, the biological significance of most 21 nonsynonymous editing sites in animals remains largely unknown. Recently, genome-wide 22 A-to-I editing was found to occur mainly in the coding regions and specifically during sexual 23 reproduction in the wheat scab fungus Fusarium graminearum that lacks ADAR orthologs. In 24 this study, we found that both the frequency and editing level of nonsynonymous editing is 25 significantly higher than those of synonymous editing, suggesting that nonsynonymous editing is 26 generally beneficial and under positive selection in F. graminearum. We also showed that 27 nonsynonymous editing favorably targets functionally more important and more conserved genes, 28 but at less-conserved sites, indicating that the RNA editing system is adapted to fine turn protein 29 functions by avoiding potentially deleterious editing events. Furthermore, nonsynonymous 30 editing in F. graminearum was found to be under codon-specific selection and most types of 31 codon changes tend to cause amino acid substitutions with distinct physical-chemical properties 32 and smaller molecular weights, which likely have more profound impact on protein structures 33 and functions. In addition, we found that the most abundant synonymous editing of leucine 34 codons is adapted to fine turn the protein expression by increasing codon usage bias. These 35 results clearly show that A-to-I RNA editing in fungi is generally adaptive and recoding RNA 36 editing may play an important role in sexual development in filamentous ascomycetes. 37. CC-BY-ND 4.0 International license not peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was .