Draft genome of the filarial nematode parasite Brugia malayi - PubMed (original) (raw)

Comparative Study

. 2007 Sep 21;317(5845):1756-60.

doi: 10.1126/science.1145406.

Shiliang Wang, David Spiro, Elisabet Caler, Qi Zhao, Jonathan Crabtree, Jonathan E Allen, Arthur L Delcher, David B Guiliano, Diego Miranda-Saavedra, Samuel V Angiuoli, Todd Creasy, Paolo Amedeo, Brian Haas, Najib M El-Sayed, Jennifer R Wortman, Tamara Feldblyum, Luke Tallon, Michael Schatz, Martin Shumway, Hean Koo, Steven L Salzberg, Seth Schobel, Mihaela Pertea, Mihai Pop, Owen White, Geoffrey J Barton, Clotilde K S Carlow, Michael J Crawford, Jennifer Daub, Matthew W Dimmic, Chris F Estes, Jeremy M Foster, Mehul Ganatra, William F Gregory, Nicholas M Johnson, Jinming Jin, Richard Komuniecki, Ian Korf, Sanjay Kumar, Sandra Laney, Ben-Wen Li, Wen Li, Tim H Lindblom, Sara Lustigman, Dong Ma, Claude V Maina, David M A Martin, James P McCarter, Larry McReynolds, Makedonka Mitreva, Thomas B Nutman, John Parkinson, José M Peregrín-Alvarez, Catherine Poole, Qinghu Ren, Lori Saunders, Ann E Sluder, Katherine Smith, Mario Stanke, Thomas R Unnasch, Jenna Ware, Aguan D Wei, Gary Weil, Deryck J Williams, Yinhua Zhang, Steven A Williams, Claire Fraser-Liggett, Barton Slatko, Mark L Blaxter, Alan L Scott

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Comparative Study

Draft genome of the filarial nematode parasite Brugia malayi

Elodie Ghedin et al. Science. 2007.

Abstract

Parasitic nematodes that cause elephantiasis and river blindness threaten hundreds of millions of people in the developing world. We have sequenced the approximately 90 megabase (Mb) genome of the human filarial parasite Brugia malayi and predict approximately 11,500 protein coding genes in 71 Mb of robustly assembled sequence. Comparative analysis with the free-living, model nematode Caenorhabditis elegans revealed that, despite these genes having maintained little conservation of local synteny during approximately 350 million years of evolution, they largely remain in linkage on chromosomal units. More than 100 conserved operons were identified. Analysis of the predicted proteome provides evidence for adaptations of B. malayi to niches in its human and vector hosts and insights into the molecular basis of a mutualistic relationship with its Wolbachia endosymbiont. These findings offer a foundation for rational drug design.

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Figures

Fig. 1

Fig. 1

Genome organization of B. malayi in comparison with C. elegans. (A) Genes on the eight largest B. malayi scaffolds. The upper part of each scaffold cartoon represents genes in conserved operons (black) or _B. malayi_–specific operons (red) or genes not in operons (gray). The lower part indicates genes with orthologs in C. elegans, colored to indicate the C. elegans chromosome on which the ortholog is located. (B) Numbers of genes on the longest B. malayi scaffolds that have orthologs on each of the six C. elegans chromosomes. (C) Distribution on the six chromosomes of C. elegans of orthologs of B. malayi genes. Orthologs map to both the conserved, central cores of the autosomes and to the less well conserved genes on the autosome arms. (D) Relative arrangements of the genes on B. malayi scaffold 14979 and their orthologs on C. elegans chromosome 3. Forward-and reverse-strand genes are distinguished (forward on top, reverse below). Red rectangles correspond to putative B. malayi operons, and black rectangles correspond to conserved operon structures.

Fig. 2

Fig. 2

Operon diversity in the genome of Brugia malayi. The cartoon shows the structure of four putative B. malayi operons (scale is shown in base pairs). Gene transcriptional orientations are shown with colored arrows, and the C. elegans chromosome on which the ortholog is contained is indicated (II, green; IV, dark purple; V, light purple, or none, grey), along with the peptide identification number (table S2). C. elegans orthologs are aligned below the B. malayi contigs, and their gene names and operon identifiers are shown. The angled double bars show gaps in the C. elegans genomic DNA; the relative size of the gap is indicated. (A) Four predicted B. malayi genes, annotated as “hypothetical,” have orthologs in a C. elegans operon. The C. elegans ortholog of the second gene is found on a different chromosome; the ortholog of E02H1.4 has not been identified within the B. malayi genome sequence. (B) In C. elegans, the orthologs of these genes are found in operons adjacent to each other but in opposing transcriptional orientations. (C) The C. elegans orthologs of genes found in this operon are relatively close to each other but are not in an operon. (D) The C. elegans ortholog of the first gene is not in the operon while the downstream gene (independently verified GenBank accession CAD22104) has no identifiable C. elegans ortholog.

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