Gene duplication and the evolution of snake venom toxins

Gene duplication is a rare event in eukaryotic genomes and has been suggested as the major source of novel genetic material. Estimates of the rate of gene duplication in vertebrates vary from 1 gene per 100 to 1 gene per 1000 per million years and the most common fate for a duplicate gene is the loss of its function. However, in some cases a duplicate gene is retained in the population and undergoes either subfunctionalisation (where the two duplicates divide the sum of the ancestral role(s) between them) or neofunctionalisation (where one of the duplicates assumes a new role, independent of the ancestral function). This latter process of evolving an entirely new function is known to be incredibly rare and there are few conclusive examples of it in the literature.

The venom of advanced snakes has been hypothesized to have originated and diversified via gene duplication. Specifically, it has been suggested that both the origin of venom and the later evolution of novelty in venom has occurred as a result of the duplication of a gene encoding a non-venom physiological or “body” protein that is subsequently recruited, via gene regulatory changes, into the venom gland, where natural selection can act on randomly occurring mutations to develop and/or increase toxicity. In short, it has been proposed that snake venom diversifies via repeated gene duplication and neofunctionalisation, a somewhat surprising finding given the apparent rarity of both of these events.

Therefore, the hypothesis concerning the evolution of snake venom is very unlikely and should be regarded with caution, it is nonetheless often assumed to be established fact, hindering research into the true origins of snake venom toxins. To critically evaluate this hypothesis Hargreaves et al. (2014) generated transcriptomic data for body tissues and salivary and venom glands from five species of venomous and non-venomous reptiles. The comparative transcriptomic analysis of these data reveals that snake venom does not evolve via the hypothesized process of duplication and recruitment of genes encoding body proteins. Instead the results show that many proposed venom toxins are in fact expressed in a wide variety of body tissues, including the salivary gland of non-venomous reptiles and that these genes have therefore been restricted to the venom gland following duplication, not recruited. Thus snake, venom evolves via the duplication and subfunctionalisation of genes encoding existing salivary proteins. These results highlight the danger of the elegant and intuitive “just-so story” in evolutionary biology

Hargreaves AD, Swain MT, Hegarty MJ, Logan DW,  Mulley JF. 2014.  Restriction and recruitment – gene duplication and the origin and evolution of snake venom toxins. Genome Biology and Evolution Advance Access10.1093/gbe/evu166.

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