Abstract
BackgroundGene duplication followed by functional divergence has long been hypothesized to be the main source of molecular novelty. Convincing examples of neofunctionalization, however, remain rare. Snake venom phospholipase A2 genes are members of large multigene families with many diverse functions, thus they are excellent models to study the emergence of novel functions after gene duplications.ResultsHere, I show that positive Darwinian selection and neofunctionalization is common in snake venom phospholipase A2 genes. The pattern of gene duplication and positive selection indicates that adaptive molecular evolution occurs immediately after duplication events as novel functions emerge and continues as gene families diversify and are refined. Surprisingly, adaptive evolution of group-I phospholipases in elapids is also associated with speciation events, suggesting adaptation of the phospholipase arsenal to novel prey species after niche shifts. Mapping the location of sites under positive selection onto the crystal structure of phospholipase A2 identified regions evolving under diversifying selection are located on the molecular surface and are likely protein-protein interactions sites essential for toxin functions.ConclusionThese data show that increases in genomic complexity (through gene duplications) can lead to phenotypic complexity (venom composition) and that positive Darwinian selection is a common evolutionary force in snake venoms. Finally, regions identified under selection on the surface of phospholipase A2 enzymes are potential candidate sites for structure based antivenin design.
Highlights
Gene duplication followed by functional divergence has long been hypothesized to be the main source of molecular novelty
The results indicate that adaptive evolution is common in snake venom Phospholipase A2s (PLA2) genes and is associated with the evolution of new toxin functions and speciation events, demonstrating that molecular adaptation has played a pervasive role in the evolution of snakes and their venom arsenal
Gene duplication and speciation history To study the molecular evolution of snake venom PLA2 genes, I compiled a dataset of 83 group-I and 90 group-II
Summary
Gene duplication followed by functional divergence has long been hypothesized to be the main source of molecular novelty. Snake venom phospholipase A2 genes are members of large multigene families with many diverse functions, they are excellent models to study the emergence of novel functions after gene duplications. Snake venom PLA2s are members of large multigene families with diverse pharmacological activities including neurotoxic, myotoxic, cardiotoxic, anticoagulant and hemolytic effects [2]. These diverse activities evolved from an ancestral nontoxic PLA2 by a process of repeated gene duplication followed by functional divergence. The surface of PLA2s forms a scaffold for adaptive modification that has been used to generate a diverse array of pharmacological effects through a process of neofunctionalization (the generation of new protein functions that were not the primary function of the ancestral protein)
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