Primate β-defensins - Structure, Function and Evolution

Sergio      Crovella; Nikolinka      Antcheva; Igor      Zelezetsky; Michele      Boniotto; Sabrina      Pacor; Maria   Vittoria Verga   Falzacappa; Alessandro      Tossi

Abstract

Host defense peptides (HDPs) are endogenous antibiotics that play a multifunctional role in the innate immunity of mammals. Among these, βdefensins contribute to mucosal and epithelial defense, also acting as signal molecules for cellular components of innate and adaptive immunity. Numerous members of this family have been identified in mammalian and avian species, and genomic studies in human and mouse indicate a considerable complexity in their gene organization. Recent reports on the evolution of primate and rodent members of this family indicate quite a complex pattern of variation. In this review we briefly discuss the evolution of mammalian βdefensins in relation to other types of defensins, and then concentrate on the evolution of βdefensins 1 to 4 in primates. In particular, the surprisingly varied patterns of evolution, which range from neutral or weakly purifying, to positive selection to a high level of conservation are analyzed in terms of possible genetics, structural or functional implications, as well as to observed variations on the antimicrobial activity in vitro. The role of polymorphisms in the genes encoding for these host defense peptides in determining susceptibility to human diseases are also briefly considered.

Keywords: defensin, antimicrobial peptide, host defense, innate immunity, molecular evolution

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