Promiscuous RNA editing in lncRNA roX1 is generally nonadaptive.

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 noncoding 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 nonselective, 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 nonadaptive signal, individual editing sites in roX1 may still be adaptive, contingent on supporting experimental evidence.