For the past 20 years, the Clusters of Orthologous Genes (COG) database had been a popular tool for microbial genome annotation and comparative genomics. Initially created for the purpose of evolutionary classification of protein families, the COG have been used, apart from straightforward functional annotation of sequenced genomes, for such tasks as (i) unification of genome annotation in groups of related organisms; (ii) identification of missing and/or undetected genes in complete microbial genomes; (iii) analysis of genomic neighborhoods, in many cases allowing prediction of novel functional systems; (iv) analysis of metabolic pathways and prediction of alternative forms of enzymes; (v) comparison of organisms by COG functional categories; and (vi) prioritization of targets for structural and functional characterization. Here we review the principles of the COG approach and discuss its key advantages and drawbacks in microbial genome analysis.

UNLABELLED: An analysis of the distribution of the Na(+)-translocating ATPases/ATP synthases among microbial genomes identified an atypical form of the F(1)F(o)-type ATPase that is present in the archaea Methanosarcina barkeri and M. acetivorans, in a number of phylogenetically diverse marine and halotolerant bacteria and in pathogens Burkholderia spp. In complete genomes, representatives of this form (referred to here as N-ATPase) are always present as second copies, in addition to the typical proton-translocating ATP synthases. The N-ATPase is encoded by a highly conserved atpDCQRBEFAG operon and its subunits cluster separately from the equivalent subunits of the typical F-type ATPases. N-ATPase c subunits carry a full set of sodium-binding residues, indicating that most of these enzymes are Na(+)-translocating ATPases that likely confer on their hosts the ability to extrude Na(+) ions. Other distinctive properties of the N-ATPase operons include the absence of the delta subunit from its cytoplasmic sector and the presence of two additional membrane subunits, AtpQ (formerly gene 1) and AtpR (formerly gene X). We argue that N-ATPases are an early-diverging branch of membrane ATPases that, similarly to the eukaryotic V-type ATPases, do not synthesize ATP. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

UNLABELLED: Sporulation in low-G+C gram-positive bacteria (Firmicutes) is an important survival mechanism that involves up to 150 genes, acting in a highly regulated manner. Many sporulation genes have close homologs in non-sporulating bacteria, including cyanobacteria, proteobacteria and spirochaetes, indicating that their products play a wider biological role. Most of them have been characterized as regulatory proteins or enzymes of peptidoglycan turnover; functions of others remain unknown but they are likely to have a general role in cell division and/or development. We have compiled a list of such widely conserved sporulation and germination proteins with poorly characterized functions, ranked them by the width of their phylogenetic distribution, and performed detailed sequence analysis and, where possible, structural modeling aimed at estimating their potential functions. Here we report the results of sequence analysis of Bacillus subtilis spore germination protein GerM, suggesting that it is a widespread cell development protein, whose function might involve binding to peptidoglycan. GerM consists of two tandem copies of a new domain (designated the GERMN domain) that forms phylum-specific fusions with two other newly described domains, GERMN-associated domains 1 and 2 (GMAD1 and GMAD2). Fold recognition reveals a beta-propeller fold for GMAD1, while ab initio modeling suggests that GMAD2 adopts a fibronectin type III fold. SpoVS is predicted to adopt the AlbA archaeal chromatin protein fold, which suggests that it is a DNA-binding protein, most likely a novel transcriptional regulator. SUPPLEMENTARY INFORMATION: Supplementary data are available at ftp://ftp.ncbi.nih.gov/pub/galperin/Sporulation.html.

Recent studies identified c-di-GMP as a universal bacterial secondary messenger regulating biofilm formation, motility, production of extracellular polysaccharide and multicellular behavior in diverse bacteria. However, except for cellulose synthase, no protein has been shown to bind c-di-GMP and the targets for c-di-GMP action remain unknown. Here we report identification of the PilZ ("pills") domain (Pfam domain PF07238) in the sequences of bacterial cellulose synthases, alginate biosynthesis protein Alg44, proteins of enterobacterial YcgR and firmicute YpfA families, and other proteins encoded in bacterial genomes and present evidence indicating that this domain is (part of) the long-sought c-di-GMP-binding protein. Association of the PilZ domain with a variety of other domains, including likely components of bacterial multidrug secretion system, could provide clues to multiple functions of the c-di-GMP in bacterial pathogenesis and cell development.

The cyanobacterium Anabaena (Nostoc) PCC 7120 responds to starvation for nitrogen compounds by differentiating approximately every 10th cell in the filament into nitrogen-fixing cells called heterocysts. Heterocyst formation is subject to complex regulation, which involves an unusual response regulator PatA that contains a CheY-like phosphoacceptor (receiver, REC) domain at its C-terminus. PatA-like response regulators are widespread in cyanobacteria; one of them regulates phototaxis in Synechocystis PCC 6803. Sequence analysis of PatA revealed, in addition to the REC domain, a previously undetected, conserved domain, which we named PATAN (after PatA N-terminus), and a potential helix-turn-helix (HTH) domain. PATAN domains are encoded in a variety of environmental bacteria and archaea, often in several copies per genome, and are typically associated with REC, Roadblock and other signal transduction domains, or with DNA-binding HTH domains. Many PATAN domains contain insertions of a small additional domain, termed alpha-clip, which is predicted to form a four-helix bundle. PATAN domains appear to participate in protein-protein interactions that regulate gliding motility and processes of cell development and differentiation in cyanobacteria and some proteobacteria, such as Myxococcus xanthus and Geobacter sulfurreducens.

Article Free Access Share on Genome analysis using clusters of orthologous groups (COGs) Authors: Eugene V. Koonin National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MDView Profile , Roman L. Tatusov National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MDView Profile , Michael Y. Galperin National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MDView Profile , Michael N. Rosanov National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MDView Profile Authors Info & Claims RECOMB '98: Proceedings of the second annual international conference on Computational molecular biologyMarch 1998 Pages 135–139https://doi.org/10.1145/279069.279106Published:01 March 1998Publication History 1citation518DownloadsMetricsTotal Citations1Total Downloads518Last 12 Months27Last 6 weeks3 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF