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The distributed-genome hypothesis (DGH) states that pathogenic bacteria possess a supragenome that is much larger than the genome of any single bacterium and that these pathogens utilize genetic recombination and a large, noncore set of genes as a means of diversity generation. We sequenced the genomes of eight nasopharyngeal strains of Streptococcus pneumoniae isolated from pediatric patients with upper respiratory symptoms and performed quantitative genomic analyses among these and nine publicly available pneumococcal strains. Coding sequences from all strains were grouped into 3,170 orthologous gene clusters, of which 1,454 (46%) were conserved among all 17 strains. The majority of the gene clusters, 1,716 (54%), were not found in all strains. Genic differences per strain pair ranged from 35 to 629 orthologous clusters, with each strain's genome containing between 21 and 32% noncore genes. The distribution of the orthologous clusters per genome for the 17 strains was entered into the finite-supragenome model, which predicted that (i) the S. pneumoniae supragenome contains more than 5,000 orthologous clusters and (ii) 99% of the orthologous clusters (ϳ3,000) that are represented in the S. pneumoniae population at frequencies of >0.1 can be identified if 33 representative genomes are sequenced. These extensive genic diversity data support the DGH and provide a basis for understanding the great differences in clinical phenotype associated with various pneumococcal strains. When these findings are taken together with previous studies that demonstrated the presence of a supragenome for Streptococcus agalactiae and Haemophilus influenzae, it appears that the possession of a distributed genome is a common host interaction strategy.Streptococcus pneumoniae is a gram-positive bacterium commonly found in the nasopharynges of healthy persons, predominantly children. In addition to its commensal form, S. pneumoniae is also a major cause of morbidity and mortality worldwide. S. pneumoniae infection can cause meningitis and bacteremia, as well as many mucosal diseases such as pneumonia, sinusitis, and otitis media (OM). Worldwide, S. pneumoniae infections are estimated to result in 1.1 million deaths a year, predominantly from pneumonia, and even in the United States pneumococcus disease is one of the top 10 causes of death (21). The economic burden associated with S. pneumoniae infections is tremendous, because it is the causative agent for 30 to 50% of OM infections worldwide, and in the United States alone the cost of OM, which is the most prevalent infectious disease among children, is estimated at $5 billion annually (5, 12).S. pneumoniae played a critical role in the demonstration that DNA is the hereditary genetic material. In 1944 Avery and colleagues showed that DNA is the transforming factor identified by Griffith as being capable of making avirulent S. pneumoniae lethal (1). Since then, S. pneumoniae has served as a model organism for the study of bacterial transformation. It contains an inducible system for the...

FLAN (short for FLu ANnotation), the NCBI web server for genome annotation of influenza virus (http://www.ncbi.nlm.nih.gov/genomes/FLU/Database/annotation.cgi) is a tool for user-provided influenza A virus or influenza B virus sequences. It can validate and predict protein sequences encoded by an input flu sequence. The input sequence is BLASTed against a database containing influenza sequences to determine the virus type (A or B), segment (1 through 8) and subtype for the hemagglutinin and neuraminidase segments of influenza A virus. For each segment/subtype of the viruses, a set of sample protein sequences is maintained. The input sequence is then aligned against the corresponding protein set with a ‘Protein to nucleotide alignment tool’ (ProSplign). The translated product from the best alignment to the sample protein sequence is used as the predicted protein encoded by the input sequence. The output can be a feature table that can be used for sequence submission to GenBank (by Sequin or tbl2asn), a GenBank flat file, or the predicted protein sequences in FASTA format. A message showing the length of the input sequence, the predicted virus type, segment and subtype for the hemagglutinin and neuraminidase segments of Influenza A virus will also be displayed.

As more and more complete bacterial genome sequences become available, the genome annotation of previously sequenced genomes may become quickly outdated. This is primarily due to the discovery and functional characterization of new genes. We have reannotated the recently published genome of Shewanella oneidensis with the following results: 51 new genes have been identified, and functional annotation has been added to the 97 genes, including 15 new and 82 existing ones with previously unassigned function. The identification of new genes was achieved by predicting the protein coding regions using the HMM-based program GeneMark.hmm. Subsequent comparison of the predicted gene products to the non-redundant protein database using BLAST and the COG (Clusters of Orthologous Groups) database using COGNITOR provided for the functional annotation.

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