Cross-species analysis of the mammalian beta-defensin gene family: presence of syntenic gene clusters and preferential expression in the male reproductive tract

Physiol Genomics. 2005 Sep 21;23(1):5-17. doi: 10.1152/physiolgenomics.00104.2005. Epub 2005 Jul 20.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antimicrobial Cationic Peptides / chemistry
  • Chromosome Mapping
  • Cluster Analysis
  • Computational Biology
  • Defensins / chemistry*
  • Dogs
  • Exons
  • Gastrointestinal Tract / metabolism
  • Gene Expression Regulation, Developmental
  • Genitalia, Male / metabolism
  • Genomics / methods
  • Humans
  • Immunity, Innate
  • Introns
  • Male
  • Mice
  • Models, Genetic
  • Molecular Sequence Data
  • Multigene Family
  • Pan troglodytes
  • Phylogeny
  • Protein Structure, Tertiary
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Software
  • Species Specificity
  • Untranslated Regions
  • beta-Defensins / metabolism
  • beta-Defensins / physiology*


  • Antimicrobial Cationic Peptides
  • DEFB4A protein, human
  • Defensins
  • Untranslated Regions
  • beta-Defensins