Origin and evolution of a deadly neurotoxin in pitviper venom

Garcia, Ramses Alejandro Rosales

ramsesr@clemson.edu

Parkinson, Christopher L

Department of Biological Sciences

Clemson University

Clemson, South Carolina USA

The Phospholipases A2 (PLA2s) toxin family is a primary component of the venom of many snakes. These toxins, along with other venom components, are organized via tandem repeats between sets of conserved surrounding genes. This organization suggests that PLA2s have undergone several gene duplications and losses, complicating the tracking of their evolutionary origins, especially in the absence of genomic data. Various processes, including the potential influence of Transposable Elements (TEs), have been proposed to drive the gain and loss of these toxin genes. The evolutionary origin of Crotoxin-like neurotoxic PLA2s is a topic of ongoing debate. Crotoxin-like neurotoxins are found in several genera in the Americas and one in Asia (Gloydius). The prevailing hypothesis suggests a single origin of these neurotoxins in the most recent common ancestor (MRCA) of Gloydius and New World pitvipers, followed by multiple losses. However, the possibility of multiple independent origins has also been proposed, though data supporting this are limited. To investigate the origin of Crotoxin-like neurotoxin genes, we analyzed existing and newly sequenced genomes, encompassing most of the genera known to express these toxins. Our results do not support the classification of Crotoxin subunit genes as independent orthogroups, thus supporting the hypothesis of multiple origins. Phylogenetic analysis indicates at least two independent origins for each subunit. Additionally, we found that, similar to Snake Venom Serine Proteases (SVMPs), TEs are associated with the expression control regions of PLA2s.