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      The genome sequence of the malaria mosquito Anopheles gambiae.

      Science (New York, N.Y.)

      Animals, Anopheles, classification, genetics, parasitology, physiology, Biological Evolution, Blood, Chromosome Inversion, Chromosomes, Artificial, Bacterial, Computational Biology, DNA Transposable Elements, Digestion, Drosophila melanogaster, Enzymes, chemistry, metabolism, Expressed Sequence Tags, Feeding Behavior, Gene Expression Regulation, Genes, Insect, Genetic Variation, Genome, Haplotypes, Humans, Insect Proteins, Insect Vectors, Malaria, Falciparum, transmission, Molecular Sequence Data, Mosquito Control, Physical Chromosome Mapping, Plasmodium falciparum, growth & development, Polymorphism, Single Nucleotide, Proteome, Sequence Analysis, DNA, Species Specificity, Transcription Factors

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          Abstract

          Anopheles gambiae is the principal vector of malaria, a disease that afflicts more than 500 million people and causes more than 1 million deaths each year. Tenfold shotgun sequence coverage was obtained from the PEST strain of A. gambiae and assembled into scaffolds that span 278 million base pairs. A total of 91% of the genome was organized in 303 scaffolds; the largest scaffold was 23.1 million base pairs. There was substantial genetic variation within this strain, and the apparent existence of two haplotypes of approximately equal frequency ("dual haplotypes") in a substantial fraction of the genome likely reflects the outbred nature of the PEST strain. The sequence produced a conservative inference of more than 400,000 single-nucleotide polymorphisms that showed a markedly bimodal density distribution. Analysis of the genome sequence revealed strong evidence for about 14,000 protein-encoding transcripts. Prominent expansions in specific families of proteins likely involved in cell adhesion and immunity were noted. An expressed sequence tag analysis of genes regulated by blood feeding provided insights into the physiological adaptations of a hematophagous insect.

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          Most cited references 40

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          Comparative genomics of the eukaryotes.

          A comparative analysis of the genomes of Drosophila melanogaster, Caenorhabditis elegans, and Saccharomyces cerevisiae-and the proteins they are predicted to encode-was undertaken in the context of cellular, developmental, and evolutionary processes. The nonredundant protein sets of flies and worms are similar in size and are only twice that of yeast, but different gene families are expanded in each genome, and the multidomain proteins and signaling pathways of the fly and worm are far more complex than those of yeast. The fly has orthologs to 177 of the 289 human disease genes examined and provides the foundation for rapid analysis of some of the basic processes involved in human disease.
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            G protein-coupled receptors in Anopheles gambiae.

            We used bioinformatic approaches to identify a total of 276 G protein-coupled receptors (GPCRs) from the Anopheles gambiae genome. These include GPCRs that are likely to play roles in pathways affecting almost every aspect of the mosquito's life cycle. Seventy-nine candidate odorant receptors were characterized for tissue expression and, along with 76 putative gustatory receptors, for their molecular evolution relative to Drosophila melanogaster. Examples of lineage-specific gene expansions were observed as well as a single instance of unusually high sequence conservation.
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              Immunity-related genes and gene families in Anopheles gambiae.

              We have identified 242 Anopheles gambiae genes from 18 gene families implicated in innate immunity and have detected marked diversification relative to Drosophila melanogaster. Immune-related gene families involved in recognition, signal modulation, and effector systems show a marked deficit of orthologs and excessive gene expansions, possibly reflecting selection pressures from different pathogens encountered in these insects' very different life-styles. In contrast, the multifunctional Toll signal transduction pathway is substantially conserved, presumably because of counterselection for developmental stability. Representative expression profiles confirm that sequence diversification is accompanied by specific responses to different immune challenges. Alternative RNA splicing may also contribute to expansion of the immune repertoire.
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                Author and article information

                Journal
                12364791
                10.1126/science.1076181

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