Identification, characterization, and evolution of a primate β-defensin gene cluster

Abstract

Defensins are members of a large diverse family of cationic antimicrobial peptides that share a signature pattern consisting of six conserved cysteine residues. Defensins have a wide variety of functions and their disruption has been implicated in various human diseases. Here we report the characterization of DEFB119-DEFB123, five genes in the human b-defensin cluster locus on chromosome 20q11.1. The genomic structures of DEFB121 and DEFB122 were determined in silico. Sequences of the five macaque orthologs were obtained and expression patterns of the genes were analyzed in humans and macaque by semiquantitative reverse transcription polymerase chain reaction. Expression was restricted to the male reproductive tract. The genes in this cluster are differentially regulated by androgens. Evolutionary analyses suggest that this cluster originated by a series of duplication events and by positive selection. The evolutionary forces driving the proliferation and diversification of these defensins may be related to reproductive specialization and/or the host-parasite coevolutionary process.

Comparative genomic analysis of a mammalian β-defensin gene cluster

“…Previously, we described the epididymal sperm binding protein DEFB118, a potent antibacterial agent and lead member of the ␤-defensin gene cluster on human chromosome 20q (38,54,81). Here, we report the discovery and characterization of the orthologous cluster in mouse.…”

“…With the findings of Hughes and Yeager (26) that positive selection for changes at the amino acid level are driving the evolution of mammalian defensin genes, several hypotheses have emerged to explain structure-function relationships and the evolutionary divergence of these multiclustered genes (4,5,11,40,44,48,53,54,59,60,73). Previously, we described the epididymal sperm binding protein DEFB118, a potent antibacterial agent and lead member of the ␤-defensin gene cluster on human chromosome 20q (38,54,81).…”

“…They are antimicrobial agents [reviewed by Ganz (15)] and fertility promoters (83,86). More than 40 ␤-defensins identified in humans are organized on three different chromosomes in five syntenic clusters (53,54,55,58,60). Orthologs of ␤-defensins were identified in other vertebrates including rodents, dog, ruminants, and primates by computational predictions and experimental evidence (27-29, 44, 73, 74, 85).…”

Antibacterial Activity of Four Human Beta-Defensins: HBD-19, HBD-23, HBD-27, and HBD-29

“…This study examined the antibacterial properties of four human β-defensins-HBD-19, 23, 27, and 29-that are normally expressed, at least at the RNA level, in the male reproductive tract [19][20][21]. Because the epididymis is anatomically continuous with the urethra, host defense against ascending bacterial pathogens is pertinent in the protection of spermatozoa from bacterial contamination.…”

“…These peptides were chosen based on their common origin in the epithelial cell layer of the testis and epididymis [19][20][21]. Although these peptides differ in primary structure from known β-defensin peptides, they share a conserved arrangement of six cysteine residues with previously studied β-defensins and may therefore play important roles in defense against invading microbes in the male reproductive tract.…”