RESUMO
The laboratory rat (Rattus norvegicus) is an indispensable tool in experimental medicine and drug development, having made inestimable contributions to human health. We report here the genome sequence of the Brown Norway (BN) rat strain. The sequence represents a high-quality 'draft' covering over 90% of the genome. The BN rat sequence is the third complete mammalian genome to be deciphered, and three-way comparisons with the human and mouse genomes resolve details of mammalian evolution. This first comprehensive analysis includes genes and proteins and their relation to human disease, repeated sequences, comparative genome-wide studies of mammalian orthologous chromosomal regions and rearrangement breakpoints, reconstruction of ancestral karyotypes and the events leading to existing species, rates of variation, and lineage-specific and lineage-independent evolutionary events such as expansion of gene families, orthology relations and protein evolution.
Assuntos
Evolução Molecular , Genoma , Genômica , Ratos Endogâmicos BN/genética , Animais , Composição de Bases , Centrômero/genética , Cromossomos de Mamíferos/genética , Ilhas de CpG/genética , Elementos de DNA Transponíveis/genética , DNA Mitocondrial/genética , Duplicação Gênica , Humanos , Íntrons/genética , Masculino , Camundongos , Modelos Moleculares , Mutagênese , Polimorfismo de Nucleotídeo Único/genética , Sítios de Splice de RNA/genética , RNA não Traduzido/genética , Ratos , Sequências Reguladoras de Ácido Nucleico/genética , Retroelementos/genética , Análise de Sequência de DNA , Telômero/genéticaRESUMO
Comparison of the genomes and proteomes of the two diptera Anopheles gambiae and Drosophila melanogaster, which diverged about 250 million years ago, reveals considerable similarities. However, numerous differences are also observed; some of these must reflect the selection and subsequent adaptation associated with different ecologies and life strategies. Almost half of the genes in both genomes are interpreted as orthologs and show an average sequence identity of about 56%, which is slightly lower than that observed between the orthologs of the pufferfish and human (diverged about 450 million years ago). This indicates that these two insects diverged considerably faster than vertebrates. Aligned sequences reveal that orthologous genes have retained only half of their intron/exon structure, indicating that intron gains or losses have occurred at a rate of about one per gene per 125 million years. Chromosomal arms exhibit significant remnants of homology between the two species, although only 34% of the genes colocalize in small "microsyntenic" clusters, and major interarm transfers as well as intra-arm shuffling of gene order are detected.
Assuntos
Anopheles/genética , Drosophila melanogaster/genética , Genoma , Proteoma , Animais , Anopheles/química , Anopheles/fisiologia , Evolução Biológica , Inversão Cromossômica , Cromossomos/genética , Análise por Conglomerados , Mecanismo Genético de Compensação de Dose , Proteínas de Drosophila/química , Proteínas de Drosophila/genética , Proteínas de Drosophila/fisiologia , Drosophila melanogaster/química , Drosophila melanogaster/fisiologia , Éxons , Ordem dos Genes , Genes de Insetos , Proteínas de Insetos/química , Proteínas de Insetos/genética , Proteínas de Insetos/fisiologia , Íntrons , Mapeamento Físico do Cromossomo , Estrutura Terciária de Proteína , Pseudogenes , Homologia de Sequência do Ácido Nucleico , Especificidade da Espécie , SinteniaRESUMO
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.