Medically important differences in snake venom composition are dictated by distinct postgenomic mechanisms

TLDR

The toxic composition of snake venom varies between species, with major medical implications for treating snakebite victims, largely due to differences in toxin‑encoding genes in the genome or venom gland. The study investigates how postgenomic mechanisms influence venom composition. It analyzes transcription, translation, and posttranslational modifications of toxin genes. Venom variation between related species results from a complex interaction of genetic and postgenomic factors, leading to significant differences in venom‑induced pathology, lethality, and antivenom efficacy.

Abstract

Significance The toxic composition of snake venom varies between species. Such variation can have major medical implications for the treatment of human snakebite victims. Venom variation is largely attributed to differences in toxin-encoding genes present in the genome or venom gland of snakes. Here, we demonstrate that mechanisms affecting the transcription, translation, and posttranslational modification of toxins also significantly contribute to the diversity of venom protein composition. Venom variation observed between related snake species is therefore the result of a complex interaction between a variety of genetic and postgenomic factors acting on toxin genes. Ultimately, this variation results in significant differences in venom-induced pathology and lethality and can undermine the efficacy of antivenom therapies used to treat human snakebite victims.