THE HUMAN BETA-DEFENSIN-1 AND ALPHA-DEFENSINS ARE ENCODED BY ADJACENTGENES - 2 PEPTIDE FAMILIES WITH DIFFERING DISULFIDE TOPOLOGY SHARE A COMMON ANCESTRY

We clotted a novel human beta-defensin gene and determined its full-le ngth cDNA sequence. The entire gene spanned more than 7 kb and include d a large 6962-bp intron. The 362-bp cDNA encoded a prepropeptide that corresponded precisely to the recently identified human beta-defensin HBD-1, an antimicrobial peptide implicated in the resistance of epith elial surfaces to microbial colonization. By two-color fluorescence in situ hybridization on both metaphase chromosome and released chromati n fiber, HBD-1 gene (DEFB1 in HUGO/GDB nomenclature) mapped to chromos omal region 8p23.1-p23.2 in close proximity (within 100-150 kb) to the gene for the human neutrophil alpha-defensin HNP-1 (DEFA1). Thus, des pite a complete lack of DNA sequence similarity and despite difference s in their disulfide-pairing pattern, the alpha- and beta-families app ear to have evolved from a common premammalian defensin gene. (C) 1997 Academic Press.