Browsing by Author "Hague, Michael T. J."

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    Gene Conversion Facilitates the Adaptive Evolution of Self-Resistance in Highly Toxic Newts
    Gendreau, Kerry L.; Hornsby, Angela D.; Hague, Michael T. J.; McGlothlin, Joel W. (Oxford Academic, 2021-10)
    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.
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    Sex linkage of the skeletal muscle sodium channel gene (SCN4A) explains apparent deviations from Hardy–Weinberg equilibrium of tetrodotoxin-resistance alleles in garter snakes (Thamnophis sirtalis)
    Gendreau, Kerry L.; Hague, Michael T. J.; Feldman, Chris R.; Brodie, Edmund D., Jr.; Brodie, Edmund D. III; McGlothlin, Joel W. (Springer Nature, 2020-02-28)
    The arms race between tetrodotoxin-bearing Pacific newts (Taricha) and their garter snake predators (Thamnophis) in western North America has become a classic example of coevolution, shedding light on predator-prey dynamics, the molecular basis of adaptation, and patterns of convergent evolution. Newts are defended by tetrodotoxin (TTX), a neurotoxin that binds to voltage-gated sodium channels (Nav proteins), arresting electrical activity in nerves and muscles and paralyzing would-be predators. However, populations of the common garter snake (T. sirtalis) have overcome this defense, largely through polymorphism at the locus SCN4A, which renders the encoded protein (Nav1.4) less vulnerable to TTX. Previous work suggests that SCN4A commonly shows extreme deviations from Hardy–Weinberg equilibrium (HWE) in these populations, which has been interpreted as the result of intense selection imposed by newts. Here we show that much of this apparent deviation can be attributed to sex linkage of SCN4A. Using genomic data and quantitative PCR, we show that SCN4A is on the Z chromosome in Thamnophis and other advanced snakes. Taking Z-linkage into account, we find that most apparent deviations from HWE can be explained by female hemizygosity rather than low heterozygosity. Sex linkage can affect mutation rates, selection, and drift, and our results suggest that Z-linkage of SCN4A may make significant contributions to the overall dynamics of the coevolutionary arms race between newts and snakes.