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 et al. (2020), 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), Dryad, Dataset, https://doi.org/10.5061/dryad.x95x69pf1
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.
qPCR data measured from genomic DNA from 6 Thamnophis sirtalis individuals (3 males and 3 females). Here, we compare ortholog copy numbers in females versus males for all 9 members of the voltage-gated sodium channel (SCN) gene family, known Z-linked gene TANC2, as well as the gene GH1, which is physically linked to SCN4A, using single-copy gene EEF1A1 as a normalizer. These data are summarized in Figure 1 of the paper.
qPCR data measured from genomic DNA from 10 Thamnophis sirtalis individuals (5 males and 5 females) from different populations in the western United States with varying levels of tetrodotoxin resistance. Here, we compare ortholog copy numbers in females versus males for voltage-gated sodium channel (SCN) genes SCN4A and SCN9A and known Z-linked gene TANC2, using single-copy gene EEF1A1 as a normalizer. These data are summarized in Figure 2 of the paper.
Summary of the sexes and genotypes at the tetrodotoxin binding region (DIV p-loop) of the SCN4A gene obtained from DNA samples of 270 Thamnophis sirtalis individuals from 16 different populations in the western United States. These data are summarized in Figure 3 of the paper. DNA sequences can be found in the NCBI PopSet database (https://www.ncbi.nlm.nih.gov/popset) under accession numbers MT043460 - MT043727.
Society for the Study of Evolution, Award: PAV23GAA
National Science Foundation, Award: DEB 1601296
National Science Foundation, Award: IOS 1355221
National Science Foundation, Award: DEB 0922251
National Science Foundation, Award: DEB 1457463