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 VEGF-A. We evaluated two scenarios for the original recruitment of nontoxin 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.

毒液是蛇的一项关键的适应性创新，非毒液基因如何成为毒素库的一部分是一个重要的进化问题。虽然这个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很少被探索。为了研究毒素招募的过程，我们对一种临床相关的蝰蛇（Bothrops jararaca）的基因组进行了测序。除了生成包含编码 12 个毒素家族的基因规范结构的路线图外，我们还推断出其基因座的大部分祖先基因。我们发现的证据表明：1) 蛇毒金属蛋白酶 (SVMP) 和磷脂酶 A ₂ (PLA2) 在基因组上已扩大到与其无毒祖先的接近程度； 2）丝氨酸蛋白酶是通过选择一个本地基因而产生的，该基因也产生蜥蜴吉拉毒素，然后扩展； 3)源自C型利尿钠肽基因骨架的缓激肽增强肽； 4) VEGF-F 是从 PGF 样基因中选出的，而不是从 VEGF-A 中选出的。我们评估了蛇毒非毒素基因最初招募的两种情况：1）基因座祖先基因复制和2）基因座祖先基因直接选择。第一个解释了两种重要毒素（SVMP 和 PLA2）的起源，而第二个解释了更多毒液成分的出现。总体而言，我们的结果支持局部组装毒液库的想法，其中临床上最相关的毒素家族通过后基因复制而扩展，无论它们是源于复制还是基因共选。