Molecular mechanisms underlying early functional divergence in snake venom inferred from the genomes of two pitviper...

The molecular mechanisms that underlie adaptive divergence in complex traits can be assessed in traits like animal venoms where variation in gene sequence and expression levels can be directly linked to functional divergence in phenotypes. We used novel metrics for measuring functional divergence based on amino acid variation to assess the impact of coding sequence evolution, gene duplication and loss, and expression variation on the divergence in venom between sister species in two lineages of pitvipers.

In both lineages, coding sequence and expression variation made significant contributions to overall functional divergence whereas genic variation was less important. Locus-specific analyses of two multigene families that encode important venom proteins (serine proteases and metalloproteases) showed that (1) There were differences between lineages in the distributions of locus effect size on functional divergence between Sistrurus (many loci with similar effects) and Bothrops (loci with either small or large effects); (2) A small number of loci were under strong positive selection, but only in serine proteases was the intensity of selection positively correlated with contributions to functional divergence in venom. (3) Patterns of overall serine protease and metalloprotease expression differed between lineages, but there was no association between expression levels of individual genes and contributions to divergence.

Our results show that the genetic underpinnings of early adaptive divergence in snake venoms are multifaceted and vary across lineages. Broadly, sequence and expression divergence both have substantial effects on functional divergence and each of these mechanisms has greater impacts than genic variation.