The Deep Origin and Recent Loss of Venom Toxin Genes in Rattlesnakes

Abstract

SUMMARY The genetic origin of novel traits is a central but challenging puzzle in evolutionary biology. Among snakes, phospholipase A2 (PLA2)-related toxins have evolved in different lineages to function as potent neurotoxins, myotoxins, or hemotoxins. Here, we traced the genomic origin and evolution of PLA2 toxins by examining PLA2 gene number, organization, and expression in both neurotoxic and non-neurotoxic rattlesnakes. We found that even though most North American rattlesnakes do not produce neurotoxins, the genes of a specialized heterodimeric neurotoxin predate the origin of rattlesnakes and were present in their last common ancestor (~22 mya). The neurotoxin genes were then deleted independently in the lineages leading to the Western Diamondback (Crotalus atrox) and Eastern Diamondback (C. adamanteus) rattlesnakes (~6 mya), while a PLA2 myotoxin gene retained in C. atrox was deleted from the neurotoxic Mojave rattlesnake (C. scutulatus; ~4 mya). The rapid evolution of PLA2 gene number appears to be due to transposon invasion that provided a template for non-allelic homologous recombination.

Targeted Sequencing of Venom Genes from Cone Snail Genomes Improves Understanding of Conotoxin Molecular Evolution

“…S4, Supplementary Material online). This result is in line with past studies showing that gene turnover is a fundamental characteristic shaping species' genic venom content (Duda and Palumbi 1999;Chang and Duda 2012;Dowell et al 2016). We note a few limitations to the data used to examine gene turnover.…”

Rattling the border wall: Pathophysiological implications of functional and proteomic venom variation between Mexican and US subspecies of the desert rattlesnake Crotalus scutulatus

“…This study also reinforces neurotoxicity as a plesiotypic feature of C. scutulatus ssp ., as suggested elsewhere (such as Dowell et al, 2016) with populations lacking this function (such as Pima County, AZ) representing a derived state. This derived state may be considered a reversal condition back to the Type I (high levels of metalloprotease activity) from the Type II condition (neurotoxin rich) (Mackessy, 2010).…”

Venom Evolution: Gene Loss Shapes Phenotypic Adaptation

“…In a wider context, this study also provides one of only a few well-described examples of how gene loss can be associated with adaptive changes to specific phenotypes [17,18]. Dowell et al [2] go one step further by predicting the mechanism responsible for causing genotypic variation in toxin genes. They propose that non-allelic homologous recombination was likely responsible for causing the genetic rearrangements that led to both the ancestral duplication and more recent loss of rattlesnake PLA 2 genes.…”

“…Dowell et al [2] suggest that this loss of neurotoxicity is likely adaptive, and that dietary variation and/or predator/prey interactions might be responsible for driving the observed genotypic variation. This is not an unreasonable assumption given prior reports of correlations between diet and venom composition [1,19] and evidence of prey (and some predator) species developing strong resistance to viperid venoms [20].…”

“…Dowell et al [2] have addressed some of these fundamental questions by studying toxin-encoding genes in North American rattlesnakes (Viperidae: Crotalus spp.). Rattlesnakes are an ideal model for studying venom variation.…”