RT Journal Article SR Electronic T1 Gene conversion facilitates the adaptive evolution of self-resistance in highly toxic newts JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.03.25.437018 DO 10.1101/2021.03.25.437018 A1 Kerry L Gendreau A1 Angela D Hornsby A1 Michael TJ Hague A1 Joel W McGlothlin YR 2021 UL http://biorxiv.org/content/early/2021/03/25/2021.03.25.437018.abstract AB Taricha newts contain high concentrations of the deadly toxin TTX as an antipredator defense, requiring them to be physiologically resistant to their own toxin. Here, we reconstruct the origins of TTX self-resistance by sequencing the voltage-gated sodium channel (SCNA) gene family, the target of TTX, in newts and related salamanders. We show that extreme resistance in newts consists of a mixture of ancient changes and lineage-specific substitutions and that the nonsynonymous substitution rate is elevated in newts, suggesting positive selection. We also identify a novel exon duplication within SCN4A encoding an expressed TTX-binding site. Two resistance-conferring changes within newts appear to have spread via nonallelic gene conversion: in one case, one codon was copied between paralogs, and in the second, multiple substitutions were homogenized between the duplicate exons of SCN4A. Our results demonstrate that gene conversion can accelerate the coordinated evolution of gene families in response to selection.Competing Interest StatementThe authors have declared no competing interest.