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Discovery of five conserved beta -defensin gene clusters using a computational search strategy.

ABSTRACT: 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.

SUBMITTER: Schutte BC

PROVIDER: S-EPMC122330 | biostudies-literature | 2002 Feb

REPOSITORIES: biostudies-literature

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Discovery of five conserved beta -defensin gene clusters using a computational search strategy.

Schutte Brian C BC 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

Proceedings of the National Academy of Sciences of the United States of America 20020201 4

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 ...[more]

PMID: 11854508

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Project description:Gene clusters are groups of genes that are co-locally conserved across various genomes, not necessarily in the same order. Their discovery and analysis is valuable in tasks such as gene annotation and prediction of gene interactions, and in the study of genome organization and evolution. The discovery of conserved gene clusters in a given set of genomes is a well studied problem, but with the rapid sequencing of prokaryotic genomes a new problem is inspired. Namely, given an already known gene cluster that was discovered and studied in one genomic dataset, to identify all the instances of the gene cluster in a given new genomic sequence. Thus, we define a new problem in comparative genomics, denoted PQ-TREE SEARCH that takes as input a PQ-tree T representing the known gene orders of a gene cluster of interest, a gene-to-gene substitution scoring function h, integer arguments [Formula: see text] and [Formula: see text], and a new sequence of genes S. The objective is to identify in S approximate new instances of the gene cluster; These instances could vary from the known gene orders by genome rearrangements that are constrained by T, by gene substitutions that are governed by h, and by gene deletions and insertions that are bounded from above by [Formula: see text] and [Formula: see text], respectively. We prove that PQ-TREE SEARCH is NP-hard and propose a parameterized algorithm that solves the optimization variant of PQ-TREE SEARCH in [Formula: see text] time, where [Formula: see text] is the maximum degree of a node in T and [Formula: see text] is used to hide factors polynomial in the input size. The algorithm is implemented as a search tool, denoted PQFinder, and applied to search for instances of chromosomal gene clusters in plasmids, within a dataset of 1,487 prokaryotic genomes. We report on 29 chromosomal gene clusters that are rearranged in plasmids, where the rearrangements are guided by the corresponding PQ-trees. One of these results, coding for a heavy metal efflux pump, is further analysed to exemplify how PQFinder can be harnessed to reveal interesting new structural variants of known gene clusters.

Dataset Information

Discovery of five conserved beta -defensin gene clusters using a computational search strategy.

Publications

Discovery of five conserved beta -defensin gene clusters using a computational search strategy.

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