Evolution of primate α and θ defensins revealed by analysis of genomes

Defensins are endogenous peptides with cysteine-rich antimicrobial ability that contribute to host defence against bacterial, fungal and viral infections. There are three subfamilies of defensins in primates: alpha, beta and theta-defensins. alpha-defensins are most present in neutrophils and Paneth cells; beta-defensins are involved in protecting the skin and the mucous membranes of the respiratory, genitourinary and gastrointestinal tracts; and theta-defensins are physically distinguished as the only known fully-cyclic peptides of animal origin, which are first isolated from rhesus macaques. All three kinds of defensins have six conserved cysteines, three intramolecular disulfide bonds, a net positive charge, and beta-sheet regions. alpha and theta-defensins are closely related, comparative amino acid sequences showed that the difference between them is that theta-defensins have an additional stop codon limits the initial defensin domain peptides to 12 residues. Humans, chimpanzees and gorillas do not produce theta-defensin peptides due to a premature stop codon present in the signal sequence of all theta-defensin pseudogenes. By using comprehensive computational searches, here we report the discovery of complete repertoires of the alpha and theta-defensin gene family in ten primate species. Consistent with previous studies, our phylogenetic analyses showed all primate theta-defensins evident formed one distinct clusters evolved from alpha-defensins. beta-defensins are ancestors of both alpha and theta-defensins. Human has two copies of DEFA1 and DEFT1P, and two extra DEFA3 and DEFA10P genes compared with gorilla. As different primates inhabit in quite different ecological niches, the production of species-specific alpha and theta-defensins and these highly evolved theta-defensins in old world monkeys would presumably allow them to better respond to the specific microbial challenges that they face.