Nachtigall Pedro G, Nystrom Gunnar S, Broussard Emilie M, Wray Kenneth P, Junqueira-de-Azevedo Inácio L M, Parkinson Christopher L, Margres Mark J, Rokyta Darin R
Department of Biological Science, Florida State University, Tallahassee, FL, USA.
Laboratório de Toxinologia Aplicada, CeTICS, Instituto Butantan, São Paulo, SP, Brazil.
Mol Biol Evol. 2025 Apr 1;42(4). doi: 10.1093/molbev/msaf058.
Of all mutational mechanisms contributing to phenotypic variation, structural variants are both among the most capable of causing major effects as well as the most technically challenging to identify. Intraspecific variation in snake venoms is widely reported, and one of the most dramatic patterns described is the parallel evolution of streamlined neurotoxic rattlesnake venoms from hemorrhagic ancestors by means of deletion of snake venom metalloproteinase (SVMP) toxins and recruitment of neurotoxic dimeric phospholipase A2 (PLA2) toxins. While generating a haplotype-resolved, chromosome-level genome assembly for the eastern diamondback rattlesnake (Crotalus adamanteus), we discovered that our genome animal was heterozygous for a ∼225 Kb deletion containing six SVMP genes, paralleling one of the two steps involved in the origin of neurotoxic rattlesnake venoms. Range-wide population-genomic analysis revealed that, although this deletion is rare overall, it is the dominant homozygous genotype near the northwestern periphery of the species' range, where this species is vulnerable to extirpation. Although major SVMP deletions have been described in at least five other rattlesnake species, C. adamanteus is unique in not additionally gaining neurotoxic PLA2s. Previous work established a superficially complementary north-south gradient in myotoxin (MYO) expression based on copy number variation with high expression in the north and low in the south, yet we found that the SVMP and MYO genotypes vary independently, giving rise to an array of diverse, novel venom phenotypes across the range. Structural variation, therefore, forms the basis for the major axes of geographic venom variation for C. adamanteus.
在所有导致表型变异的突变机制中，结构变异既能产生重大影响，识别起来在技术上又最具挑战性。蛇毒的种内变异被广泛报道，其中描述的最显著模式之一是，通过缺失蛇毒金属蛋白酶（SVMP）毒素并招募神经毒性二聚体磷脂酶A2（PLA2）毒素，出血性祖先的蛇毒平行进化为简化的神经毒性响尾蛇毒。在为东部菱斑响尾蛇（Crotalus adamanteus）生成单倍型解析的染色体水平基因组组装时，我们发现我们的基因组动物对于一个包含六个SVMP基因的约225 Kb缺失是杂合的，这与神经毒性响尾蛇毒起源所涉及的两个步骤之一相似。全范围的群体基因组分析表明，虽然这种缺失总体上很罕见，但它是该物种分布范围西北边缘附近的主要纯合基因型，在那里该物种易受灭绝影响。虽然在至少其他五个响尾蛇物种中也描述过主要的SVMP缺失，但东部菱斑响尾蛇的独特之处在于没有额外获得神经毒性PLA2。先前的研究基于拷贝数变异建立了一个表面上互补的南北肌毒素（MYO）表达梯度，北部高表达，南部低表达，但我们发现SVMP和MYO基因型独立变化，在整个分布范围内产生了一系列多样的、新颖的毒液表型。因此，结构变异构成了东部菱斑响尾蛇地理毒液变异主要轴的基础。
