看似无关的特征通常具有相同的潜在分子机制,潜在地产生多效性关系,从而选择塑造一个性状可以同时损害另一个性状。虽然这种功能权衡预计会影响进化结果,它们在自然界中的实际相关性被基因型之间的模糊联系所掩盖,表型,和健身。这里,我们描述了在捕食者-食饵系统中可能控制关键适应和协同进化动力学的功能权衡。几条吊袜带蛇(Thamnophisspp。)种群已经进化出对河豚毒素(TTX)的抗性,它们猎物体内的强大化学防御,有毒new(Tarichaspp.).蛇通过在蛇骨骼肌电压门控钠通道(NaV1.4)的孔中的毒素结合位点发生的突变来实现TTX抗性。我们假设这些突变损害了基本的NaV功能,产生分子权衡,最终应该扩大到妥协的有机性能。我们调查了两种具有独特且独立进化的突变的蛇物种的生物物理成本,这些突变赋予了TTX抗性。我们显示了电生理学证据,表明由毒素抗性等位基因编码的骨骼肌钠通道在功能上受到损害。此外,具有抗性基因型的蛇的骨骼肌表现出降低的机械性能。最后,建立这些钠通道变体的分子稳定性模型部分解释了电生理和肌肉损伤。最终,有利于毒素抗性的适应性遗传变化似乎对钠通道功能产生负面影响,骨骼肌力量,和有机表现。这些在细胞和器官水平上的功能权衡似乎是在抗性蛇中观察到的运动缺陷的基础,并且可以解释整个景观中抗毒素等位基因在种群水平上的成功差异。最终塑造了蛇-牛顿共同进化的轨迹。
Seemingly unrelated traits often share the same underlying molecular mechanisms, potentially generating a pleiotropic relationship whereby selection shaping one trait can simultaneously compromise another. While such functional trade-offs are expected to influence evolutionary outcomes, their actual relevance in nature is masked by obscure links between genotype, phenotype, and fitness. Here, we describe functional trade-offs that likely govern a key adaptation and coevolutionary dynamics in a predator-prey system. Several garter snake (Thamnophis spp.) populations have evolved resistance to tetrodotoxin (TTX), a potent chemical defense in their prey, toxic newts (Taricha spp.). Snakes achieve TTX resistance through mutations occurring at toxin-binding sites in the pore of snake skeletal muscle voltage-gated sodium channels (NaV1.4). We hypothesized that these mutations impair basic NaV functions, producing molecular trade-offs that should ultimately scale up to compromised organismal performance. We investigate biophysical costs in two snake species with unique and independently evolved mutations that confer TTX resistance. We show electrophysiological evidence that skeletal muscle sodium channels encoded by toxin-resistant alleles are functionally compromised. Furthermore, skeletal muscles from snakes with resistance genotypes exhibit reduced mechanical performance. Lastly, modeling the molecular stability of these sodium channel variants partially explains the electrophysiological and muscle impairments. Ultimately, adaptive genetic changes favoring toxin resistance appear to negatively impact sodium channel function, skeletal muscle strength, and organismal performance. These functional trade-offs at the cellular and organ levels appear to underpin locomotor deficits observed in resistant snakes and may explain variation in the population-level success of toxin-resistant alleles across the landscape, ultimately shaping the trajectory of snake-newt coevolution.