PT - JOURNAL ARTICLE AU - Kerry L Gendreau AU - Angela D Hornsby AU - Michael TJ Hague AU - Joel W McGlothlin TI - Gene conversion facilitates the adaptive evolution of self-resistance in highly toxic newts AID - 10.1101/2021.03.25.437018 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.03.25.437018 4099 - http://biorxiv.org/content/early/2021/03/25/2021.03.25.437018.short 4100 - http://biorxiv.org/content/early/2021/03/25/2021.03.25.437018.full 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.