Venom toxin genes are tandem-arrayed beyond gene-family-size expectations in four venomous bilaterian species

Abstract

Toxin genes of venomous animals often lie in tandem arrays, but large gene families cluster whatever their function, so how much of this architecture is specific to toxins is unclear. We asked whether toxin genes cluster more than non-toxin gene families of the same size and, if so, what carries the excess. Across five venomous genomes, anchored on a new chromosome-level genome of the centipede Scolopendra mutilans with a 12-individual venom-gland proteome, the clustering enrichment of toxin genes fell from 14-31-fold against random genes to about 2-6-fold against size-matched non-toxin families in the four bilaterian species (centipede, snake, spider, scorpion), but did not disappear: the matched odds ratio remained above 1 across three gene-family definitions and, under the primary definition, windows of 25-200 kb, matching on within-family sequence similarity and, in the snake, a published venom-gene annotation, whereas evidence in the sea anemone was insufficient to establish an excess. The excess was spread across many toxin families and was carried mainly by homologous copies lying next to one another. In evaluable families, phylogenetically closest copies were physically closer than their families' layout predicts in toxin and non-toxin tandem families alike; tandem toxin copies did not differ detectably in expression output; and a pre-specified congener comparison had too little information to be evaluated. Toxin genes are thus tandem-arrayed beyond family-size expectations in the four sampled bilaterian species, and the excess lies mainly in homologous arrays; the present comparisons do not distinguish whether such arrays form more often or persist longer.