Contains, data, code, and figures for "Many options, few solutions: over 60 million years snakes converged on a few optimal venom formulations"
Gene expression changes contribute to complex trait variations in both individuals and populations. However, the evolution of gene expression underlying complex traits over macroevolutionary timescales remains poorly understood. Being comprised of proteinaceous cocktails, snake venoms are unique in that the expression of each toxin can be quantified and mapped to a distinct genomic locus and traced for up to tens of millions of years. Using a phylogenetic generalized linear mixed model we analysed expression data of toxin genes from 52 snake species spanning the three venomous snake families, and estimated phylogenetic covariance, which acts as a measure of evolutionary constraint. We find that evolution of toxin combinations is not constrained. However, while all combinations are in principle possible, the actual dimensionality of phylomorphic space is low, with envenomation strategies focused around only four major toxin families: metalloproteases, three-finger toxins, serine proteases, and phospholipases A2. While most extant snakes prioritize either a single or a combination of major toxin families they are repeatedly recruited and lost. We find that over macroevolutionary timescales the venom phenotypes was not shaped by phylogenetic constraints, which include important microevolutionary constraints such as epistasis and pleiotropy, but more likely by ecological filtering that permits a small number of optimal solutions. As a result, phenotypic optima were repeatedly attained by distantly related species. These results indicate that venoms evolve by selection on biochemistry of prey envenomation, which permit diversity through parallelism, and impose strong limits, since only a few of the theoretically possible strategies seem to work well and are observed in extant snakes.
Keywords: gene expression, generalized linear mixed model, macroevolution, parallel evolution, venom