CALL FOR PAPERS Comparative Genomics Cross-species analysis of the mammalian -defensin gene family: presence of syntenic gene clusters and preferential expression in the male reproductive tract

Patil, Amar A., Yibin Cai, Yongming Sang, Frank Blecha, and Guolong Zhang. Cross-species analysis of the mammalian -defensin gene family: presence of syntenic gene clusters and preferential expression in the male reproductive tract. Physiol Genomics 23: 5–17, 2005. First published July 20, 2005; 10.1152/physiolgenomics.00104.2005.—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 -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 carboxyterminal mature sequences or untranslated regions. Alternatively, spliced isoforms have also been found with several -defensins. Furthermore, all -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 -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, RT-PCR revealed that all but one rat -defensin transcript 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.