Tracking the recruitment and evolution of snake toxins using the evolutionary context provided by the Bothrops jararaca genome
Tracking the recruitment and evolution of snake toxins using the evolutionary context provided by the Bothrops jararaca genome
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DOI：
10.1073/pnas.2015159118
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发表时间：
2021-05-18
影响因子：
11.1
通讯作者：
Junqueira-de-Azevedo, Inacio L. M.
中科院分区：
文献类型：
--
作者：
Almeida, Diego Dantas;Viala, Vincent Louis;Junqueira-de-Azevedo, Inacio L. M.
毒液是蛇类适应性进化的关键，而非毒液基因是如何被吸收成为毒素武器库的一部分是一个重要的进化问题。虽然这一过程已经通过毒素序列的系统发育重建进行了研究，但毒素基因的基因组背景提供的证据仍然较少探索。为了研究毒素募集的过程，我们对一种临床相关的蝰蛇Bothrops jararaca的基因组进行了测序。除了产生具有编码12个毒素家族的基因的典型结构的路线图之外，我们还推断了其位点的大多数祖先基因。我们发现的证据表明：1）蛇毒金属蛋白酶（SVMP）和磷脂酶A2（PLA 2）在基因组邻近其无毒祖先的位置上进行了扩展; 2）丝氨酸蛋白酶是通过选择一个本地基因而产生的，该基因也会产生蜥蜴吉拉毒素，然后进行扩展; 3）缓激肽增强肽起源于C型利尿钠肽基因骨架;（4）VEGF-F来自PGF样基因，而不是VEGFA。我们评估了蛇毒非毒素基因最初募集的两种情况：1）在位点祖先基因重复和2）在位点祖先基因直接共选择。第一个解释了两种重要毒素（SVMP和PLA 2）的起源，而第二个解释了大量毒液成分的出现。总的来说，我们的研究结果支持了本地组装的毒液库的想法，其中最临床相关的毒素家族通过后基因复制扩展，无论它们是否起源于复制或基因co-option。
Venom is a key adaptive innovation in snakes, and how nonvenom genes were co-opted to become part of the toxin arsenal is a significant evolutionary question. While this process has been investigated through the phylogenetic reconstruction of toxin sequences, evidence provided by the genomic context of toxin genes remains less explored. To investigate the process of toxin recruitment, we sequenced the genome of Bothrops jararaca, a clinically relevant pitviper. In addition to producing a road map with canonical structures of genes encoding 12 toxin families, we inferred most of the ancestral genes for their loci. We found evidence that 1) snake venom metalloproteinases (SVMPs) and phospholipases A2 (PLA2) have expanded in genomic proximity to their nonvenomous ancestors; 2) serine proteinases arose by co-opting a local gene that also gave rise to lizard gilatoxins and then expanded; 3) the bradykinin-potentiating peptides originated from a C-type natriuretic peptide gene backbone; and 4) VEGF-F was co-opted from a PGF-like gene and not from VEGFA. We evaluated two scenarios for the original recruitment of non toxin genes for snake venom: 1) in locus ancestral gene duplication and 2) in locus ancestral gene direct co-option. The first explains the origins of two important toxins (SVMP and PLA2), while the second explains the emergence of a greater number of venom components. Overall, our results support the idea of a locally assembled venom arsenal in which the most clinically relevant toxin families expanded through posterior gene duplications, regardless of whether they originated by duplication or gene co-option.