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.
Subject(s)
Anopheles/genetics , Genes, Insect , Genome , Sequence Analysis, DNA , Animals , Anopheles/classification , Anopheles/parasitology , Anopheles/physiology , Biological Evolution , Blood , Chromosome Inversion , Chromosomes, Artificial, Bacterial , Computational Biology , DNA Transposable Elements , Digestion , Drosophila melanogaster/genetics , Enzymes/chemistry , Enzymes/genetics , Enzymes/metabolism , Expressed Sequence Tags , Feeding Behavior , Gene Expression Regulation , Genetic Variation , Haplotypes , Humans , Insect Proteins/chemistry , Insect Proteins/genetics , Insect Proteins/physiology , Insect Vectors/genetics , Insect Vectors/parasitology , Insect Vectors/physiology , Malaria, Falciparum/transmission , Molecular Sequence Data , Mosquito Control , Physical Chromosome Mapping , Plasmodium falciparum/growth & development , Polymorphism, Single Nucleotide , Proteome , Species Specificity , Transcription Factors/chemistry , Transcription Factors/genetics , Transcription Factors/physiologyABSTRACT
The compact genome of Fugu rubripes has been sequenced to over 95% coverage, and more than 80% of the assembly is in multigene-sized scaffolds. In this 365-megabase vertebrate genome, repetitive DNA accounts for less than one-sixth of the sequence, and gene loci occupy about one-third of the genome. As with the human genome, gene loci are not evenly distributed, but are clustered into sparse and dense regions. Some "giant" genes were observed that had average coding sequence sizes but were spread over genomic lengths significantly larger than those of their human orthologs. Although three-quarters of predicted human proteins have a strong match to Fugu, approximately a quarter of the human proteins had highly diverged from or had no pufferfish homologs, highlighting the extent of protein evolution in the 450 million years since teleosts and mammals diverged. Conserved linkages between Fugu and human genes indicate the preservation of chromosomal segments from the common vertebrate ancestor, but with considerable scrambling of gene order.
