重建复杂适应的历史并确定其起源的进化机制是进化生物学的两个主要目标。Tarichanew,其中含有高浓度的致命毒素河豚毒素(TTX)作为抗捕食者的防御,进化出了对自我中毒的抵抗力,这是一种复杂的适应,需要改变电压门控钠通道(Nav)基因家族的六个旁系同源物,TTX的生理目标。这里,我们通过对new和相关sal的整个Nav基因家族进行测序,重建了TTX自我抗性的起源。我们表明,在六个Nav旁系同源物中的三个中,sal谱系中的中度TTX抗性在早期进化,在被提议出现的河水毒性new之前,有100个My。携带TTX的new在整个Nav基因家族中具有额外的独特取代,其提供生理TTX抗性。这些替换与正选择和宽松的纯化选择的特征一致,以及基因转换事件,这可能促进了他们的进化。我们还鉴定了Nav1.4中编码表达的TTX结合位点的新外显子重复。new内的两个抗性赋予变化似乎通过非等位基因基因转换传播:在一种情况下,在旁系同源物之间复制了一个密码子,在第二个,在Nav1.4的重复外显子之间均质化多个替换。我们的结果表明,在共同的选择压力下,基因转换可以加速基因家族的协调进化。
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.