Snake venoms are integrated systems, but abundant venom proteins evolve more rapidly.

Steven D Aird,Mandy Man-Ying Tin,Alejandro Villar-Briones,Alexander S Mikheyev,Kouki Terada,Shikha Aggarwal

doi:10.1186/s12864-015-1832-6

Abstract

BackgroundWhile many studies have shown that extracellular proteins evolve rapidly, how selection acts on them remains poorly understood. We used snake venoms to understand the interaction between ecology, expression level, and evolutionary rate in secreted protein systems. Venomous snakes employ well-integrated systems of proteins and organic constituents to immobilize prey. Venoms are generally optimized to subdue preferred prey more effectively than non-prey, and many venom protein families manifest positive selection and rapid gene family diversification. Although previous studies have illuminated how individual venom protein families evolve, how selection acts on venoms as integrated systems, is unknown.ResultsUsing next-generation transcriptome sequencing and mass spectrometry, we examined microevolution in two pitvipers, allopatrically separated for at least 1.6 million years, and their hybrids. Transcriptomes of parental species had generally similar compositions in regard to protein families, but for a given protein family, the homologs present and concentrations thereof sometimes differed dramatically. For instance, a phospholipase A2 transcript comprising 73.4 % of the Protobothrops elegans transcriptome, was barely present in the P. flavoviridis transcriptome (<0.05 %). Hybrids produced most proteins found in both parental venoms. Protein evolutionary rates were positively correlated with transcriptomic and proteomic abundances, and the most abundant proteins showed positive selection. This pattern holds with the addition of four other published crotaline transcriptomes, from two more genera, and also for the recently published king cobra genome, suggesting that rapid evolution of abundant proteins may be generally true for snake venoms. Looking more broadly at Protobothrops, we show that rapid evolution of the most abundant components is due to positive selection, suggesting an interplay between abundance and adaptation.ConclusionsGiven log-scale differences in toxin abundance, which are likely correlated with biosynthetic costs, we hypothesize that as a result of natural selection, snakes optimize return on energetic investment by producing more of venom proteins that increase their fitness. Natural selection then acts on the additive genetic variance of these components, in proportion to their contributions to overall fitness. Adaptive evolution of venoms may occur most rapidly through changes in expression levels that alter fitness contributions, and thus the strength of selection acting on specific secretome components.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1832-6) contains supplementary material, which is available to authorized users.

Highlights

While many studies have shown that extracellular proteins evolve rapidly, how selection acts on them remains poorly understood
Extracellular proteins may play a larger role in evolutionary interactions with the environment and other organisms, which should make them more likely targets of positive selection [10, 11], as predicted by coevolutionary theory [12, 13]
We benefitted from the dynamic range and accuracy of transcriptomics, while proteomic data distinguished between proteins secreted into the venom, and non-venom components, allowing us to contrast evolutionary patterns in the two classes of genes

Summary

Introduction

While many studies have shown that extracellular proteins evolve rapidly, how selection acts on them remains poorly understood. A dominant pattern observed in studies of diverse model systems, ranging from yeast to mammals, is that secreted proteins evolve faster than intracellular proteins [7,8,9,10,11]. Reasons for this phenomenon remain poorly understood. Non-adaptive explanations posit that extracellular proteins experience relaxed selection, and are more tolerant of mutations for structural, ecological, or evolutionary reasons [8, 9]. Extracellular proteins may play a larger role in evolutionary interactions with the environment and other organisms, which should make them more likely targets of positive selection [10, 11], as predicted by coevolutionary theory [12, 13]

Methods

Results

Conclusion