Gene Conversion Facilitates the Adaptive Evolution of Self-Resistance in Highly Toxic Newts.

Kerry L Gendreau,Michael T J Hague,Joel W Mcglothlin,Angela D Hornsby,John Parsch

doi:10.1093/molbev/msab182

Kerry L Gendreau, Michael T J Hague + Show 3 more

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https://doi.org/10.1093/molbev/msab182

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Abstract

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 My. 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.

Highlights

Fitting evolutionary models to molecular sequences in a phylogenetic context can help piece together the key steps in adaptive evolution and uncover the relative contributions of selection and other evolutionary mechanisms to adaptive phenotypic evolution (Smith et al 2020)
We obtained near full-length assemblies for all paralogs; a few exons containing TTX-binding sites, including exon 15 of Nav1.2 from N. viridescens and TTX Resistance in Newts . doi:10.1093/molbev/msab182
We show that TTX-bearing newts have evolved resistance to their own toxicity through multiple parallel changes in their Nav genes and that, similar to snakes that consume TTX-containing prey (McGlothlin et al 2016; Perry et al 2018), some of the resistance in this taxon is ancient, first appearing in an early salamander

Summary

Introduction

Fitting evolutionary models to molecular sequences in a phylogenetic context can help piece together the key steps in adaptive evolution and uncover the relative contributions of selection and other evolutionary mechanisms to adaptive phenotypic evolution (Smith et al 2020). Investigations into the molecular basis of convergence have revealed multiple occurrences of parallelism, where different lineages have evolved changes within the same proteins, and occasionally at the same amino acid sites, in response to shared selective pressures, such as insects that have evolved the ability to feed on toxic plants (Zhen et al 2012) and populations of ducks and humans living at high elevations (Graham and McCracken 2019). Such patterns support important roles for both positive selection and constraint in the origin of complex adaptations (reviewed by Storz 2016).

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