Data from: Domain loss facilitates accelerated evolution and neofunctionalization of duplicate snake venom metalloproteinase toxin genes

Gene duplication is a key mechanism for the adaptive evolution and neofunctionalization of gene families. Large multi-gene families often exhibit complex evolutionary histories as a result of frequent gene duplication acting in concordance with positive selection pressures. Alterations in the domain structure of genes, causing changes in the molecular scaffold of proteins, can also result in a complex evolutionary history and has been observed in functionally diverse multi-gene toxin families. Here, we investigate the role alterations in domain structure have on the tempo of evolution and neofunctionalization of multi-gene families using the snake venom metalloproteinases (SVMPs) as a model system. Our results reveal that the evolutionary history of viperid (Serpentes: Viperidae) SVMPs is repeatedly punctuated by domain loss, with the single loss of the cysteine-rich domain, facilitating the formation of P-II class SVMPs, occurring prior to the convergent loss of the disintegrin domain to form multiple P-I SVMP structures. Notably, the majority of phylogenetic branches where domain loss was inferred to have occurred exhibited highly significant evidence of positive selection in surface-exposed amino acid residues, resulting in the neofunctionalization of P-II and P-I SVMP classes. These results provide a valuable insight into the mechanisms by which complex gene families evolve and detail how the loss of domain structures can catalyse the accelerated evolution of novel gene paralogues. The ensuing generation of differing molecular scaffolds encoded by the same multi-gene family facilitates gene neofunctionalization, whilst presenting an evolutionary advantage through the retention of multiple genes capable of encoding functionally distinct proteins.

基因复制是基因家族适应性演化与新功能化的核心机制。大型多基因家族往往因频繁的基因复制与正选择压力协同作用，演化出复杂的进化历史。基因结构域的改变会引发蛋白质分子骨架的变化，同样可导致复杂演化历史，这一现象在功能多样的多基因毒素家族中已有报道。本研究以蛇毒金属蛋白酶（snake venom metalloproteinases, SVMPs）为模型系统，探究结构域改变对多基因家族演化速率与新功能化的作用。研究结果显示，蝰科（Serpentes: Viperidae）蛇毒金属蛋白酶的演化历史反复被结构域丢失事件打断：富半胱氨酸结构域的单次丢失促成了P-II类蛇毒金属蛋白酶的形成，这一事件早于去整合素结构域的趋同丢失，进而产生多种P-I类蛇毒金属蛋白酶结构。值得注意的是，绝大多数被推断发生结构域丢失的系统发育分支，其表面暴露的氨基酸残基均呈现出极强的正选择信号，最终推动了P-II与P-I类蛇毒金属蛋白酶的新功能化。本研究结果为复杂基因家族的演化机制提供了重要见解，并详细阐明了结构域丢失如何催化新型基因旁系同源物的加速演化。同一多基因家族编码的不同分子骨架的产生，不仅推动了基因新功能化，还通过保留多个可编码功能迥异蛋白质的基因，为物种带来了演化优势。