Speciation of Cone Snails and Interspecific Hyperdivergence of Their Venom Peptides: Potential Evolutionary Significance of Introns^a

Abstract

All 500 species of cone snails (Conus) are venomous predators. From a biochemical/genetic perspective, differences among Conus species may be based on the 50-200 different peptides in the venom of each species. Venom is used for prey capture as well as for interactions with predators and competitors. The venom of every species has its own distinct complement of peptides. Some of the interspecific divergence observed in venom peptides can be explained by differential expression of venom peptide superfamilies in different species and of peptide superfamily branching in various Conus lineages into pharmacologic groups with different targeting specificity. However, the striking interspecific divergence of peptide sequences is the dominant factor in the differences observed between venoms. The small venom peptides (typically 10-35 amino acids in length) are processed from larger prepropeptide precursors (ca. 100 amino acids). If interspecific comparisons are made between homologous prepropeptides, the three different regions of a Conus peptide precursor (signal sequence, pro-region, mature peptide) are found to have diverged at remarkably different rates. Analysis of synonymous and nonsynonymous substitution rates for the different segments of a prepropeptide suggests that mutation frequency varies by over an order of magnitude across the segments, with the mature toxin region undergoing the highest rate. The three sections of the prepropeptide which exhibit apparently different mutation rates are separated by introns. This striking segment-specific rate of divergence of Conus prepropeptides suggests a role for introns in evolution: exons separated by introns have the potential to evolve very different mutation rates. Plausible mechanisms that could underlie differing mutational frequency in the different exons of a gene are discussed.

Transcriptomic Messiness in the Venom Duct of Conus miles Contributes to Conotoxin Diversity

“…The O superfamily has diverse pharmacology, with -, O, ␦, ␥-, and -conotoxins targeting voltage-gated calcium, sodium, and potassium channels (38). Although most biologically active O-superfamily members characterized so far are identified from fish-hunting species (17,39), the prevalence of O-superfamily toxins in worm-hunting cone snails suggests an important role in prey capture across diverse phyla.…”

ConusVenoms: A Rich Source of Novel Ion Channel-Targeted Peptides

“…In contrast, the size range of polypeptidic toxins from other venoms is typically 40 -80 amino acids. Despite their small size, there is a remarkable interspecific sequence divergence, even between homologous conopeptides from closely related Conus species (149,193). Another striking feature of conopeptides is the presence of an unusually diverse complement of posttranslationally modified amino acids, found at a high frequency in some conopeptide families (27).…”

“…The mechanisms that lead to the conservation of the signal sequences (a conservation that extends even to the third position of codons, making even silent mutations underrepresented in this region) juxtaposed with the hyperdivergence observed in the mature toxin region (149,193) remain a subject for speculation; a variety of mechanisms leading to the observed differences in the differential rate of divergence observed for the signal sequence region, the pro region, and the mature toxin region have been proposed (25,40,49,137,149).…”

Natural selection and cultural rates of change

“…On the other hand, genes experiencing positive selection may evolve more rapidly (15). For example, genes coding for sea snail venom appear to have diverged rapidly under positive selection (16). Proposed molecular signatures for positive selection include higher between-population differences, higher frequency of derived alleles, reduction of diversity within a population or species, and longer haplotypes because linked traits are carried along in selective sweeps (15,17,18).…”