Accelerated evolution of toxin genes: Exonization and intronization in snake venom disintegrin/metalloprotease genes

• Published in: Toxicon (Oxford) Vol. 148; pp. 16 - 25
• Main Author: Kini, R. Manjunatha
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 15-06-2018
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Disintegrins - genetics; Evolution of reptile genes; Evolution, Molecular; Exons - genetics; Introns - genetics; Metalloproteases - genetics; Neofunctionalization; Origin of exons; Origin of intron; Rapid evolution of proteins; Viper Venoms - chemistry; Viper Venoms - genetics; Viperidae - genetics; Origin of exons; Evolution of reptile genes; Neofunctionalization; Origin of intron; Rapid evolution of proteins
• ISSN: 0041-0101; 1879-3150
• DOI: 10.1016/j.toxicon.2018.04.005

Toxin genes in animals undergo accelerated evolution compared to non-toxin genes to be effective and competitive in prey capture, as well as to enhance their predator defense. Several mechanisms have been proposed to explain this unusual phenomenon. These include (a) frequent mutations in exons compared to introns and nonsynonymous substitutions in exons; (b) high frequency of point mutations are due to the presence of more unstable triplets in exons compared to introns; (c) Accelerated Segment Switch in Exons to alter Targeting (ASSET); (d) Rapid Accumulation of Variations in Exposed Residues (RAVERs); (e) alteration in intron-exon boundary; (f) deletion of exon; and (g) loss/gain of domains through recombination. By systematic analyses of snake venom disintegrin/metalloprotease genes, I describe a new mechanism in the evolution of these genes through exonization and intronization. In the evolution of RTS/KTS disintegrins, a new exon (10a) is formed in intron 10 of the disintegrin/metalloprotease gene. Unlike more than 90% new exons that are from repetitive elements in introns, exon 10a originated from a non-repetitive element. To incorporate exon 10a, part of the exon 11 is intronized to retain the open reading frame. This is the first case of simultaneous exonization and intronization within a single gene. This new mechanism alters the function of toxins through drastic changes to the molecular surface via insertion of new exons and deletion of exons.
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•The first instance of exonization and intronization in the evolution of disintegrin/metalloprotease genes in snakes.•May explain sudden alteration of the molecular surface of the toxin and hence, its function.•This phenomenon will have significant impact on the evolution and neofunctionalization of toxins.