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 Gendreau, Kerry L.
A1 Hornsby, Angela D.
A1 Hague, Michael T. J.
A1 McGlothlin, Joel W.
YR 2021
UL http://biorxiv.org/content/early/2021/05/25/2021.03.25.437018.abstract
AB Reconstructing the histories of complex adaptations and identifying the evolutionary mechanisms underlying their origins are two of the primary goals of evolutionary biology. Taricha newts, which contain high concentrations of the deadly toxin tetrodotoxin (TTX) as an antipredator defense, have evolved resistance to self-intoxication, which is a complex adaptation requiring changes in six paralogs of the voltage-gated sodium channel (Nav) gene family, the physiological target of TTX. Here, we reconstruct the origins of TTX self-resistance by sequencing the entire Nav gene family in newts and related salamanders. We show that moderate TTX resistance evolved early in the salamander lineage in three of the six Nav paralogs, preceding the proposed appearance of tetrodotoxic newts by ∼100 million years. TTX-bearing newts possess additional unique substitutions across the entire Nav gene family that provide physiological TTX resistance. These substitutions coincide with signatures of positive selection and relaxed purifying selection, as well as gene conversion events, that together likely facilitated their evolution. We also identify a novel exon duplication within Nav1.4 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 Nav1.4. Our results demonstrate that gene conversion can accelerate the coordinated evolution of gene families in response to a common selection pressure.Competing Interest StatementThe authors have declared no competing interest.