Discovery of five conserved beta -defensin gene clusters using a computational search strategy.
The innate immune system includes antimicrobial peptides that protect multicellular organisms from a diverse spectrum of microorganisms. beta-Defensins comprise one important family of mammalian antimicrobial peptides. The annotation of the human genome fails to reveal the expected diversity, and a recent query of the draft sequence with the blast search engine found only one new beta-defensin gene (DEFB3). To define better the beta-defensin gene family, we adopted a genomics approach that uses hmmer, a computational search tool based on hidden Markov models, in combination with blast. This strategy identified 28 new human and 43 new mouse beta-defensin genes in five syntenic chromosomal regions. Within each syntenic cluster, the gene sequences and organization were similar, suggesting each cluster pair arose from a common ancestor and was retained because of conserved functions. Preliminary analysis indicates that at least 26 of the predicted genes are transcribed. These results demonstrate the value of a genomewide search strategy to identify genes with conserved structural motifs. Discovery of these genes represents a new starting point for exploring the role of beta-defensins in innate immunity.
Schutte
Brian C
BC
Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA.
Mitros
Joseph P
JP
Bartlett
Jennifer A
JA
Walters
Jesse D
JD
Jia
Hong Peng
HP
Welsh
Michael J
MJ
Casavant
Thomas L
TL
McCray
Paul B
PB
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D003201:Computers; D017124:Conserved Sequence; D020451:Contig Mapping; D003545:Cysteine / Q000737:chemistry; D005091:Exons; D006801:Humans; D008390:Markov Chains; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D005810:Multigene Family; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid; D012984:Software; D023083:beta-Defensins / Q000737:chemistry* / Q000235:genetics*
D023083:beta-Defensins; D003545:Cysteine