title: Domain loss facilitates accelerated evolution and neofunctionalization of duplicate snake venom metalloproteinase toxin genes.
abstract: Gene duplication is a key mechanism for the adaptive evolution and neofunctionalization of gene families. Large multigene families often exhibit complex evolutionary histories as a result of frequent gene duplication acting in concordance with positive selection pressures. Alterations in the domain structure of genes, causing changes in the molecular scaffold of proteins, can also result in a complex evolutionary history and has been observed in functionally diverse multigene toxin families. Here, we investigate the role alterations in domain structure have on the tempo of evolution and neofunctionalization of multigene families using the snake venom metalloproteinases (SVMPs) as a model system. Our results reveal that the evolutionary history of viperid (Serpentes: Viperidae) SVMPs is repeatedly punctuated by domain loss, with the single loss of the cysteine-rich domain, facilitating the formation of P-II class SVMPs, occurring prior to the convergent loss of the disintegrin domain to form multiple P-I SVMP structures. Notably, the majority of phylogenetic branches where domain loss was inferred to have occurred exhibited highly significant evidence of positive selection in surface-exposed amino acid residues, resulting in the neofunctionalization of P-II and P-I SVMP classes. These results provide a valuable insight into the mechanisms by which complex gene families evolve and detail how the loss of domain structures can catalyze the accelerated evolution of novel gene paralogues. The ensuing generation of differing molecular scaffolds encoded by the same multigene family facilitates gene neofunctionalization while presenting an evolutionary advantage through the retention of multiple genes capable of encoding functionally distinct proteins.
authors.affiliation: Alistair Reid Venom Research Unit, Liverpool School of Tropical Medicine, Liverpool, United Kingdom. n.r.casewell@liv.ac.uk
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Casewell
authors.forename: Simon C
authors.initials: SC
authors.lastname: Wagstaff
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrison
authors.forename: Camila
authors.initials: C
authors.lastname: Renjifo
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wüster
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D000818:Animals; D019143:Evolution, Molecular; D020440:Gene Duplication; D045726:Metalloproteases / Q000737:chemistry / Q000235:genetics*; D005810:Multigene Family; D010802:Phylogeny; D017434:Protein Structure, Tertiary / Q000235:genetics*; D012641:Selection, Genetic; D012910:Snake Venoms / Q000737:chemistry / Q000235:genetics*; D013329:Structure-Activity Relationship; D017819:Viperidae / Q000235:genetics*
chemical_list: D012910:Snake Venoms; D045726:Metalloproteases