The Rise and Fall of an Evolutionary Innovation: Contrasting Strategies of Venom Evolution in Ancient and Young Animals

Animal venoms are theorized to evolve under the significant influence of positive Darwinian selection in a chemical arms race scenario, where the evolution of venom resistance in prey and the invention of potent venom in the secreting animal exert reciprocal selection pressures. Venom research to date has mainly focused on evolutionarily younger lineages, such as snakes and cone snails, while mostly neglecting ancient clades (e.g., cnidarians, coleoids, spiders and centipedes). By examining genome, venom-gland transcriptome and sequences from the public repositories, we report the molecular evolutionary regimes of several centipede and spider toxin families, which surprisingly accumulated low-levels of sequence variations, despite their long evolutionary histories. Molecular evolutionary assessment of over 3500 nucleotide sequences from 85 toxin families spanning the breadth of the animal kingdom has unraveled a contrasting evolutionary strategy employed by ancient and evolutionarily young clades. We show that the venoms of ancient lineages remarkably evolve under the heavy constraints of negative selection, while toxin families in lineages that originated relatively recently rapidly diversify under the influence of positive selection. We propose that animal venoms mostly employ a ‘two-speed’ mode of evolution, where the major influence of diversifying selection accompanies the earlier stages of ecological specialization (e.g., diet and range expansion) in the evolutionary history of the species–the period of expansion, resulting in the rapid diversification of the venom arsenal, followed by longer periods of purifying selection that preserve the potent toxin pharmacopeia–the period of purification and fixation. However, species in the period of purification may re-enter the period of expansion upon experiencing a major shift in ecology or environment. Thus, we highlight for the first time the significant roles of purifying and episodic selections in shaping animal venoms.

学界普遍认为，动物毒液的演化处于达尔文正向选择（positive Darwinian selection）的强烈影响之下，该过程可类比化学军备竞赛：猎物演化出毒液抗性，分泌毒液的动物则进化出强效毒液，二者相互施加选择压力。迄今为止，毒液研究主要聚焦于蛇类、芋螺等演化历史较年轻的类群，却大多忽略了刺胞动物、头足类、蜘蛛及蜈蚣等古老演化支（clade）。本研究通过分析公共数据库中的基因组、毒液腺转录组（transcriptome）及序列数据，报道了数个蜈蚣与蜘蛛毒素家族的分子演化模式：尽管它们拥有漫长的演化历史，序列变异水平却意外偏低。本研究对覆盖整个动物界的85个毒素家族的3500余条核苷酸序列进行分子演化分析，揭示了古老与年轻演化支截然不同的演化策略。研究表明，古老类群的毒液演化受到负选择（negative selection）的强烈约束，而起源较晚的类群中的毒素家族则在正向选择的作用下快速实现序列多样化。本研究提出，动物毒液的演化大多采用“双速模式”：在物种演化历史的早期生态特化阶段（如食谱拓展与分布范围扩张），多样化选择占据主导，推动毒液武器库快速实现多样化；随后则进入更长时间的纯化选择（purifying selection）阶段，以保留强效毒素组——即纯化与固定阶段。然而，处于纯化阶段的物种若遭遇生态或环境的重大改变，可重新进入扩张阶段。综上，本研究首次阐明了纯化选择与间歇选择（episodic selection）在塑造动物毒液演化过程中的重要作用。