Deciphering APOBEC1 in Avians: Unravelling loss events and functional insights

Abstract

In vertebrates, cytidine-to-uracil (C-to-U) editing is mediated by the AID/APOBEC family of deaminases, with APOBEC1 (A1) known to catalyse precise RNA editing of apolipoprotein B (apoB) transcripts in mammals. Despite its well-characterised role in mammals, the evolutionary history and functional divergence of A1 across birds remain underexplored. Here, we investigate the evolutionary trajectory of A1 in birds, where both the presence of the gene and apoB RNA editing activity have been questioned. Through a comprehensive in silico analysis of 81 avian genomes, we identify recurrent disruptions and catalytic inactivation of A1 in multiple lineages. Comparative sequence and structural analyses reveal a lack of domains and key residues essential for RNA binding, dimerisation, and cofactor interaction, suggesting a role in DNA editing. Furthermore, genome-wide screening for A1-associated G-to-A mutations in long terminal repeat (LTR) retrotransposons demonstrates that species with higher endogenous retrovirus (ERV) loads retain more DNA editing signatures, consistent with a defensive role of A1 against retroelements. In contrast, species with low ERV content exhibit relaxed selection and frequent A1 pseudogenisation. Together, these findings support the hypothesis that DNA editing represents the ancestral function of A1, with RNA editing in mammals evolving later as an exaptation following the expansion of A3 and changes in retroviral pressures.