RT Journal Article SR Electronic T1 Repeated subfunctionalization of a modular antimicrobial peptide gene for neural function JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.02.24.432738 DO 10.1101/2021.02.24.432738 A1 M.A. Hanson A1 B. Lemaitre YR 2021 UL http://biorxiv.org/content/early/2021/10/11/2021.02.24.432738.abstract AB Antimicrobial peptides (AMPs) are host-encoded antibiotics that combat invading pathogens. However recent studies have highlighted roles for AMPs in neurological contexts suggesting functions for these defence molecules beyond infection. Here we characterize the evolution of the Drosophila Baramicin (Bara) AMP gene family. During our immune study characterizing the Baramicins, we recovered multiple Baramicin paralogs in Drosophila melanogaster and other species, united by their N-terminal IM24 domain. Strikingly, some paralogs are no longer immune-induced. A careful dissection of the Baramicin family’s evolutionary history indicates that these non-immune paralogs result from repeated events of duplication and subsequent truncation of the coding sequence from an immune-inducible ancestor. These truncations leave only the IM24 domain as the prominent gene product. Using mutation and targeted gene silencing, we demonstrate that two such genes are adapted for function in neural contexts in D. melanogaster, and show enrichment in the head for independent Baramicin genes in other species. The Baramicin evolutionary history reveals that the IM24 Baramicin domain is not strictly useful in an immune context. We thus provide a case study for how an AMP-encoding gene might play dual roles in both immune and non-immune processes via its multiple peptide products. We reflect on these findings to highlight a blind spot in the way researchers approach AMP research in in vivo contexts.Competing Interest StatementThe authors have declared no competing interest.