Lynch Vincent J
Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT 06511, USA.
BMC Evol Biol. 2007 Jan 18;7:2. doi: 10.1186/1471-2148-7-2.
Gene duplication followed by functional divergence has long been hypothesized to be the main source of molecular novelty. Convincing examples of neofunctionalization, however, remain rare. Snake venom phospholipase A2 genes are members of large multigene families with many diverse functions, thus they are excellent models to study the emergence of novel functions after gene duplications.
Here, I show that positive Darwinian selection and neofunctionalization is common in snake venom phospholipase A2 genes. The pattern of gene duplication and positive selection indicates that adaptive molecular evolution occurs immediately after duplication events as novel functions emerge and continues as gene families diversify and are refined. Surprisingly, adaptive evolution of group-I phospholipases in elapids is also associated with speciation events, suggesting adaptation of the phospholipase arsenal to novel prey species after niche shifts. Mapping the location of sites under positive selection onto the crystal structure of phospholipase A2 identified regions evolving under diversifying selection are located on the molecular surface and are likely protein-protein interactions sites essential for toxin functions.
These data show that increases in genomic complexity (through gene duplications) can lead to phenotypic complexity (venom composition) and that positive Darwinian selection is a common evolutionary force in snake venoms. Finally, regions identified under selection on the surface of phospholipase A2 enzymes are potential candidate sites for structure based antivenin design.
长期以来,人们一直推测基因复制后功能分化是分子新奇性的主要来源。然而,新功能化的令人信服的例子仍然很少。蛇毒磷脂酶A2基因是具有多种不同功能的大型多基因家族的成员,因此它们是研究基因复制后新功能出现的优秀模型。
在这里,我表明正达尔文选择和新功能化在蛇毒磷脂酶A2基因中很常见。基因复制和正选择的模式表明,随着新功能的出现,适应性分子进化在复制事件后立即发生,并随着基因家族的多样化和精细化而持续。令人惊讶的是,眼镜蛇科中I组磷脂酶的适应性进化也与物种形成事件相关,这表明在生态位转移后,磷脂酶库适应了新的猎物物种。将正选择位点的位置映射到磷脂酶A2的晶体结构上,确定在多样化选择下进化的区域位于分子表面,可能是毒素功能所必需的蛋白质-蛋白质相互作用位点。
这些数据表明,基因组复杂性的增加(通过基因复制)可以导致表型复杂性(毒液组成),并且正达尔文选择是蛇毒中常见的进化力量。最后,在磷脂酶A2酶表面选择下确定的区域是基于结构的抗蛇毒血清设计的潜在候选位点。