Cross-species analysis of the mammalian beta-defensin gene family: presence of syntenic gene clusters and preferential expression in the male reproductive tract.
Mammalian beta-defensins are an important family of innate host defense peptides with pleiotropic activities. As a first step to study the evolutionary relationship and biological role of the beta-defensin family, we identified their complete repertoires in the human, chimpanzee, mouse, rat, and dog following systemic, genome-wide computational searches. Although most beta-defensin genes are composed of two exons separated by an intron of variable length, some contain an additional one or two exons encoding an internal pro-sequence, a segment of carboxy-terminal mature sequences or untranslated regions. Alternatively, spliced isoforms have also been found with several beta-defensins. Furthermore, all beta-defensin genes are densely clustered in four to five syntenic chromosomal regions, with each cluster spanning <1.2 Mb across the five species. Phylogenetic analysis indicated that, although the majority of beta-defensins are evolutionarily conserved across species, subgroups of gene lineages exist that are specific in certain species, implying that some beta-defensins originated after divergence of these mammals from each other, while most others arose before the last common ancestor of mammals. Surprisingly, RT-PCR revealed that all but one rat beta-defensin transcript are preferentially expressed in the male reproductive tract, particularly in epididymis and testis, except that Defb4, a human beta-defensin-2 ortholog, is more restricted to the respiratory and upper gastrointestinal tracts. Moreover, most beta-defensins expressed in the reproductive tract are developmentally regulated, with enhanced expression during sexual maturation. Existence of such a vast array of beta-defensins in the male reproductive tract suggests that these genes may play a dual role in both fertility and host defense.
Patil
Amar A
AA
Department of Animal Science, Oklahoma State University, Stillwater, Oklahoma 74078, USA.
Cai
Yibin
Y
Sang
Yongming
Y
Blecha
Frank
F
Zhang
Guolong
G
D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry; D002874:Chromosome Mapping; D016000:Cluster Analysis; D019295:Computational Biology; D023082:Defensins / Q000737:chemistry*; D004285:Dogs; D005091:Exons; D041981:Gastrointestinal Tract / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005837:Genitalia, Male / Q000378:metabolism; D023281:Genomics / Q000379:methods; D006801:Humans; D007113:Immunity, Innate; D007438:Introns; D008297:Male; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D005810:Multigene Family; D002679:Pan troglodytes; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D012984:Software; D013045:Species Specificity; D020506:Untranslated Regions; D023083:beta-Defensins / Q000378:metabolism / Q000502:physiology*
D023181:Antimicrobial Cationic Peptides; C106641:DEFB4A protein, human; D023082:Defensins; D020506:Untranslated Regions; D023083:beta-Defensins