Abstract：
The evolution of venom and the selection pressures that act on toxins have been increasingly researched within toxinology in the last two decades, in part due to the exceptionally high rates of diversifying selection observed in animal toxins. In 2015, Sungar and Moran proposed the \'two-speed\' model of toxin evolution linking evolutionary age of a group to the rates of selection acting on toxins but due to a lack of data, mammals were not included as less than 30 species of venomous mammal have been recorded, represented by elusive species which produce small amounts of venom. Due to advances in genomics and transcriptomics, the availability of toxin sequences from venomous mammals has been increasing. Using branch- and site-specific selection models, we present the rates of both episodic and pervasive selection acting upon venomous mammal toxins as a group for the first time. We identified seven toxin groups present within venomous mammals, representing Chiroptera, Eulipotyphla and Monotremata: KLK1, Plasminogen Activator, Desmallipins, PACAP, CRiSP, Kunitz Domain One and Kunitz Domain Two. All but one group (KLK1) was identified by our results to be evolving under both episodic and pervasive diversifying selection with four toxin groups having sites that were implicated in the fitness of the animal by TreeSAAP (Selection on Amino Acid Properties). Our results suggest that venomous mammal ecology, behaviour or genomic evolution are the main drivers of selection, although evolutionary age may still be a factor. Our conclusion from these results indicates that mammalian toxins are following the two-speed model of selection, evolving predominately under diversifying selection, fitting in with other younger venomous taxa like snakes and cone snails-with high amounts of accumulating mutations, leading to more novel adaptions in their toxins.
摘要：
在过去的二十年中，毒液的进化和作用于毒素的选择压力在毒理学中得到了越来越多的研究，部分原因是在动物毒素中观察到的多样化选择比率异常高。2015年，Sungar和Moran提出了毒素进化的“两速”模型，将群体的进化年龄与作用于毒素的选择率联系起来，但由于缺乏数据，哺乳动物不包括在内，因为记录的有毒哺乳动物少于30种，以产生少量毒液的难以捉摸的物种为代表。由于基因组学和转录组学的进步，有毒哺乳动物的毒素序列的可用性一直在增加。使用分支和特定地点的选择模型，我们首次将对有毒哺乳动物毒素起作用的偶发性和广泛性选择的比率作为一个群体来呈现。我们确定了有毒哺乳动物中存在的七个毒素组，代表翼翅目，原脂型和单纯性：KLK1，纤溶酶原激活剂，Desmallipins，PACAP,CRiSP,Kunitz域1和Kunitz域2。根据我们的结果，除一组（KLK1）外，所有一组（KLK1）都在发生和普遍多样化选择下发展，其中四个毒素组的位点与TreeSAAP（氨基酸特性选择）的动物适应性有关。我们的结果表明，有毒哺乳动物的生态，行为或基因组进化是选择的主要驱动因素，虽然进化年龄可能仍然是一个因素。我们从这些结果得出的结论表明，哺乳动物毒素遵循两速选择模型，主要在多样化选择下演变，与其他年轻的有毒类群如蛇和锥蜗牛相适应，具有大量积累的突变，导致毒素更新颖的适应。
