Promiscuous RNA editing in lncRNA roX1 is generally non-adaptive

Abstract

Adaptation of adenosine-to-inosine (A-to-I) RNA editing has only been validated for a few nonsynonymous (recoding) sites, where the editable state confers higher fitness than the uneditable or fully-edited state. However, adaptation of non-coding RNA editing is unexplored, limiting our understanding of the significance of post-transcriptional modifications. In this study, we report extensive A-to-I editing in Drosophila lncRNA roX1, a key component of the dosage compensation pathway. Despite dramatically higher roX1 expressions in males compared to females, editing levels show minimum gender specificity, indicating non-selective, promiscuous editing. Cross-sample comparison reveals no correlation between roX1 editing levels and the extent of dosage compensation. Furthermore, Adar mutant male flies do not display abnormal dosage compensation of X chromosomal genes. These findings suggest that rampant RNA editing in roX1 is unlikely to play functional roles in dosage compensation and does not appear to offer a selective advantage over either a genomic G or an uneditable allele. Our results align with the molecular error hypothesis that the adaptive changes represent only a small fraction of the genome. Nevertheless, we do not exclude the possibility that, despite a global non-adaptive signal, individual editing sites in roX1 may still be adaptive, contingent on supporting experimental evidence.