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)
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)
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DOI：
10.1038/s41437-020-0300-5
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发表时间：
2020-02
期刊：
影响因子：
3.8
通讯作者：
Kerry L. Gendreau;Michael T. J. Hague;C. Feldman;Edmund D. Brodie;Edmund D. Brodie;J. McGlothlin
中科院分区：
文献类型：
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作者：
Kerry L. Gendreau;Michael T. J. Hague;C. Feldman;Edmund D. Brodie;Edmund D. Brodie;J. McGlothlin
北美西部带有河豚毒素的太平洋蝾螈(Taricha)和它们的吊带蛇捕食者(Thamnopits)之间的军备竞赛已成为共同进化的经典例子，揭示了捕食者-猎物动力学、适应的分子基础和收敛进化模式。河豚毒素(TTX)是一种神经毒素，它与电压门控钠通道(NavProteins)结合，阻止神经和肌肉的电活动，使潜在的捕食者瘫痪。然而，普通系带蛇(T.sirtalis)的种群已经克服了这种防御，主要是通过SCN4A位点的多态，这使得编码的蛋白质(Nav1.4)不太容易受到TTX的影响。以前的工作表明，在这些种群中，SCN4A通常表现出对Hardy-Weinberg平衡(HWE)的极端偏离，这被解释为蝾螈施加的密集选择的结果。在这里，我们表明，这种明显的偏差很大程度上可以归因于SCN4A的性别连锁。利用基因组数据和定量聚合酶链式反应，我们证明SCN4A位于Z染色体上，在食蟹类和其他高级蛇中。考虑到Z-连锁，我们发现最明显的HWE偏差可以用女性的半合子来解释，而不是低杂合度。性别连锁可以影响突变率、选择和漂移，我们的结果表明，SCN4A的Z连锁可能对纽鸟和蛇之间共同进化的军备竞赛的整体动态做出重大贡献。
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 (Navproteins), 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 locusSCN4A, which renders the encoded protein (Nav1.4) less vulnerable to TTX. Previous work suggests thatSCN4Acommonly 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 ofSCN4A. Using genomic data and quantitative PCR, we show thatSCN4Ais on the Z chromosome inThamnophisand 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 ofSCN4Amay make significant contributions to the overall dynamics of the coevolutionary arms race between newts and snakes.