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-Defensin Gene Family: Presence of Syntenic Gene Clusters and Preferential Expression in the Male Reproductive Tract
1 Department of Animal Science, Oklahoma State University, Stillwater, OK, USA
2 Department of Anatomy and Physiology, Kansas State University, Manhattan, KS, USA
* To whom correspondence should be addressed. E-mail: zguolon{at}okstate.edu.
Mammalian 
-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 -defensin family, we identified their complete repertoires in the human, chimpanzee, mouse, rat, and dog following systemic, genome-wide computational searches. Although most -defensins genes are composed of two exons separated by an intron of variable length, some contain additional one or two exons encoding an internal pro-sequence, a segment of carboxyl terminal mature sequences or untranslated regions. Alternatively spliced isoforms have also been found with several -defensins. Furthermore, all -defensin genes are densely clustered in 4-5 syntenic chromosomal regions with each cluster spanning <1.2 Mb across the five species. Phylogenetic analysis indicated that, although the majority of -defensins are evolutionarily conserved across species, subgroups of gene lineages exist that are specific in certain species, implying that some -defensins originated after divergence of these mammals from each other, while most others arose before the last common ancestor of mammals. Surprisingly, reverse transcriptase-PCR revealed that all but one rat -defensin transcripts are preferentially expressed in the male reproductive tract particularly in epididymis and testis, except that Defb4, a human -defensin-2 ortholog, is more restricted to the respiratory and upper gastrointestinal tracts. Moreover, most -defensins expressed in the reproductive tract are developmentally regulated with enhanced expression during sexual maturation. Existence of such a vast array of -defensins in the male reproductive tract suggests that these genes may play a dual role in both fertility and host defense.
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