Data from: Convergent adaptation to dangerous prey proceeds through the same first-step mutation in the garter snake Thamnophis sirtalis

Convergent phenotypes often result from similar underlying genetics, but recent work suggests convergence may also occur in the historical order of substitutions en route to an adaptive outcome. We characterized convergence in the mutational steps to two independent outcomes of tetrodotoxin (TTX) resistance in separate geographic lineages of the common garter snake (Thamnophis sirtalis) that coevolved with toxic newts. Resistance is largely conferred by amino acid changes in the skeletal muscle sodium channel (NaV1.4) that interfere with TTX-binding. We sampled variation in NaV1.4 throughout western North America and found clear evidence that TTX-resistant changes in both lineages began with the same isoleucine-valine mutation (I1561V) within the outer pore of NaV1.4. Other point mutations in the pore, shown to confer much greater resistance, accumulate later in the evolutionary progression and always occur together with the initial I1561V change. A gene tree of NaV1.4 suggests the I1561V mutations in each lineage are not identical-by-decent, but rather they arose independently. Convergence in the evolution of channel resistance is likely the result of shared biases in the two lineages of Th. sirtalis – only a few mutational routes can confer TTX resistance while maintaining the conserved function of voltage-gated sodium channels.趋同表型（convergent phenotypes）通常由相似的潜在遗传机制所产生，但近期研究表明，在通往适应性结果的演化路径中，氨基酸替换发生的历史顺序也可能出现趋同现象。我们对与有毒蝾螈协同演化的普通束带蛇（Thamnophis sirtalis）两个独立地理支系中，河豚毒素（tetrodotoxin, TTX）抗性的两种独立演化结局的突变步骤趋同性进行了表征。该抗性主要由骨骼肌钠通道（NaV1.4）中的氨基酸替换所介导，此类替换可干扰河豚毒素的结合。我们在北美西部全域采样了NaV1.4的序列变异，结果明确显示，两个支系的河豚毒素抗性相关突变均起始于NaV1.4孔道区域内的同一种异亮氨酸-缬氨酸突变（I1561V）。后续演化进程中积累的其他孔道区点突变虽可赋予更强的抗性，但始终与初始的I1561V突变相伴出现。NaV1.4的基因树分析表明，两个支系中的I1561V突变并非由共同祖先遗传而来，而是独立起源的。束带蛇两个支系的通道抗性演化出现趋同，大概率源于二者共有的演化偏向性：在维持电压门控钠通道（voltage-gated sodium channels）保守功能的前提下，仅存在少数几种可赋予河豚毒素抗性的突变路径。