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Samuel Karlin

Publications and source records attributed to Samuel Karlin.

17 recordsLinked to original sources
PubMed2006

Distinguishing features of delta-proteobacterial genomes.

We analyzed several features of five currently available delta-proteobacterial genomes, including two aerobic bacteria exhibiting predatory behavior and three anaerobic sulfate-reducing bacteria. The delta genomes are distinguished from other bacteria by several properties: (i) The delta genomes contain two "giant" S1 ribosomal protein genes in contrast to all other bacterial types, which encode a single or no S1; (ii) in most delta-proteobacterial genomes the major ribosomal protein (RP) gene cluster is near the replication terminus whereas most bacterial genomes place the major RP cluster near the origin of replication; (iii) the delta genomes possess the rare combination of discriminating asparaginyl and glutaminyl tRNA synthetase (AARS) together with the amido-transferase complex (Gat CAB) genes that modify Asp-tRNA(Asn) into Asn-tRNA(Asn) and Glu-tRNA(Gln) into Gln-tRNA(Gln); (iv) the TonB receptors and ferric siderophore receptors that facilitate uptake and removal of complex metals are common among delta genomes; (v) the anaerobic delta genomes encode multiple copies of the anaerobic detoxification protein rubrerythrin that can neutralize hydrogen peroxide; and (vi) sigma(54) activators play a more important role in the delta genomes than in other bacteria. delta genomes have a plethora of enhancer binding proteins that respond to environmental and intracellular cues, often as part of two-component systems; (vii) delta genomes encode multiple copies of metallo-beta-lactamase enzymes; (viii) a host of secretion proteins emphasizing SecA, SecB, and SecY may be especially useful in the predatory activities of Myxococcus xanthus; (ix) delta proteobacteria drive many multiprotein machines in their periplasms and outer membrane, including chaperone-feeding machines, jets for slime secretion, and type IV pili. Bdellovibrio replicates in the periplasm of prey cells. The sulfate-reducing delta proteobacteria metabolize hydrogen and generate a proton gradient by electron transport. The predicted highly expressed genes from delta genomes reflect their different ecologies, metabolic strategies, and adaptations.

Amino Acyl-tRNA Synthetases↗
PubMed2006

Genomic comparisons among gamma-proteobacteria.

Predicted highly expressed (PHX) genes are compared for 16 gamma-proteobacteria and their similarities and differences are interpreted with respect to known or predicted physiological characteristics of the organisms. Predicted highly expressed genes often reflect the organism's predominant lifestyle, habitat, nutrition sources and metabolic propensities. This technique allows to predict principal metabolic activities of the microorganisms operating in their natural habitats. Among our findings is an unusually high number of PHX enzymes acting in cell wall biosynthesis, amino acid biosynthesis and replication in the ant endosymbiont Blochmannia floridanus. We ascribe the abundance of these PHX genes to specific aspects of the relationship between the bacterium and its host. Xanthomonas campestris is unique with a very high number of PHX genes acting in flagellum biosynthesis, which may play a special role during its pathogenicity. Shewanella oneidensis possesses three protein complexes which all can function as complex I in the respiratory chain but only the Na(+)-transporting NADH:ubiquinone oxidoreductase nqr-2 operon is PHX. The PHX genes of Vibrio parahaemolyticus are consistent with the microorganism's adaptation to extremely fast growth rates. Comparative analysis of PHX genes from complex environmental genomic sequences as well as from uncultured pathogenic microbes can provide a novel, useful tool to predict global flux of matter and key intermediates.

Bacterial Proteins↗
PubMed2005

Statistical signals in bioinformatics.

The Arthur M. Sackler Colloquium of the National Academy of Sciences, "Frontiers in Bioinformatics: Unsolved Problems and Challenges," organized by David Eisenberg, Russ Altman, and myself, was held October 15-17, 2004, to provide a forum for discussing concepts and methods in bioinformatics serving the biological and medical sciences. The deluge of genomic and proteomic data in the last two decades has driven the creation of tools that search and analyze biomolecular sequences and structures. Bioinformatics is highly interdisciplinary, using knowledge from mathematics, statistics, computer science, biology, medicine, physics, chemistry, and engineering.

Animals↗
PubMed2005

Protein length in eukaryotic and prokaryotic proteomes.

We analyzed length differences of eukaryotic, bacterial and archaeal proteins in relation to function, conservation and environmental factors. Comparing Eukaryotes and Prokaryotes, we found that the greater length of eukaryotic proteins is pervasive over all functional categories and involves the vast majority of protein families. The magnitude of these differences suggests that the evolution of eukaryotic proteins was influenced by processes of fusion of single-function proteins into extended multi-functional and multi-domain proteins. Comparing Bacteria and Archaea, we determined that the small but significant length difference observed between their proteins results from a combination of three factors: (i) bacterial proteomes include a greater proportion than archaeal proteomes of longer proteins involved in metabolism or cellular processes, (ii) within most functional classes, protein families unique to Bacteria are generally longer than protein families unique to Archaea and (iii) within the same protein family, homologs from Bacteria tend to be longer than the corresponding homologs from Archaea. These differences are interpreted with respect to evolutionary trends and prevailing environmental conditions within the two prokaryotic groups.

Amino Acid Sequence↗
PubMed2005

Predicted highly expressed genes in archaeal genomes.

Based primarily on 16S rRNA sequence comparisons, life has been broadly divided into the three domains of Bacteria, Archaea, and Eukarya. Archaea is further classified into Crenarchaea and Euryarchaea. Archaea generally thrive in extreme environments as assessed by temperature, pH, and salinity. For many prokaryotic organisms, ribosomal proteins (RP), transcription/translation factors, and chaperone genes tend to be highly expressed. A gene is predicted highly expressed (PHX) if its codon usage is rather similar to the average codon usage of at least one of the RP, transcription/translation factors, and chaperone gene classes and deviates strongly from the average gene of the genome. The thermosome (Ths) chaperonin family represents the most salient PHX genes among Archaea. The chaperones Trigger factor and HSP70 have overlapping functions in the folding process, but both of these proteins are lacking in most archaea where they may be substituted by the chaperone prefoldin. Other distinctive PHX proteins of Archaea, absent from Bacteria, include the proliferating cell nuclear antigen PCNA, a replication auxiliary factor responsible for tethering the catalytic unit of DNA polymerase to DNA during high-speed replication, and the acidic RP P0, which helps to initiate mRNA translation at the ribosome. Other PHX genes feature Cell division control protein 48 (Cdc48), whereas the bacterial septation proteins FtsZ and minD are lacking in Crenarchaea. RadA is a major DNA repair and recombination protein of Archaea. Archaeal genomes feature a strong Shine-Dalgarno ribosome-binding motif more pronounced in Euryarchaea compared with Crenarchaea.

Archaea↗
PubMed2005

Genomic and proteomic comparisons between bacterial and archaeal genomes and related comparisons with the yeast and fly genomes.

Bacterial, archaeal, yeast, and fly genomes are compared with respect to predicted highly expressed (PHX) genes and several genomic properties. There is a striking difference in the status of PHX ribosomal protein (RP) genes where the archaeal genome generally encodes more RP genes and fewer PHX RPs compared with bacterial genomes. The increase in RPs in archaea and eukaryotes compared with that in bacteria may reflect a more complex set of interactions in archaea and eukaryotes in regulating translation, e.g., differences in structure requiring scaffolding of longer rRNA molecules, expanded interactions with the chaperone machinery, and, in eukaryotic interactions with endoplasmic reticulum components. The yeast genome is similar to fast-growing bacteria in PHX genes but also features several cytoskeletal genes, including actin and tropomyosin, and several signal transduction regulatory proteins from the 14.3.3 family. The most PHX genes of Drosophila encode cytoskeletal and exoskeletal proteins. We found that the preference of a microorganism for an anaerobic metabolism correlates with the number of PHX enzymes of the glycolysis pathway that well exceeds the number of PHX enzymes acting in the tricarboxylic acid cycle. Conversely, if the number of PHX enzymes of the tricarboxylic acid cycle well exceeds the PHX enzymes of glycolysis, an aerobic metabolism is preferred. Where the numbers are approximately commensurate, a facultative growth behavior prevails.

Animals↗
PubMed2005

Predicting coding potential from genome sequence: application to betaherpesviruses infecting rats and mice.

Prediction of protein-coding regions and other features of primary DNA sequence have greatly contributed to experimental biology. Significant challenges remain in genome annotation methods, including the identification of small or overlapping genes and the assessment of mRNA splicing or unconventional translation signals in expression. We have employed a combined analysis of compositional biases and conservation together with frame-specific G+C representation to reevaluate and annotate the genome sequences of mouse and rat cytomegaloviruses. Our analysis predicts that there are at least 34 protein-coding regions in these genomes that were not apparent in earlier annotation efforts. These include 17 single-exon genes, three new exons of previously identified genes, a newly identified four-exon gene for a lectin-like protein (in rat cytomegalovirus), and 10 probable frameshift extensions of previously annotated genes. This expanded set of candidate genes provides an additional basis for investigation in cytomegalovirus biology and pathogenesis.

Amino Acid Sequence↗
PubMed2004

Comparative analysis of gene expression among low G+C gram-positive genomes.

We present a comparative analysis of predicted highly expressed (PHX) genes in the low G+C Gram-positive genomes of Bacillus subtilis, Bacillus halodurans, Listeria monocytogenes, Listeria innocua, Lactococcus lactis, Streptococcus pyogenes, Streptococcus pneumoniae, Staphylococcus aureus, Clostridium acetobutylicum, and Clostridium perfringens. Most enzymes acting in glycolysis and fermentation pathways are PHX in these genomes, but not those involved in the TCA cycle and respiration, suggesting that these organisms have predominantly adapted to grow rapidly in an anaerobic environment. Only B. subtilis and B. halodurans have several TCA cycle PHX genes, whereas the TCA pathway is entirely missing from the metabolic repertoire of the two Streptococcus species and is incomplete in Listeria, Lactococcus, and Clostridium. Pyruvate-formate lyase, an enzyme critical in mixed acid fermentation, is among the highest PHX genes in all these genomes except for C. acetobutylicum (not PHX), and B. subtilis, and B. halodurans (missing). Pyruvate-formate lyase is also prominently PHX in enteric gamma-proteobacteria, but not in other prokaryotes. Phosphotransferase system genes are generally PHX with selection of different substrates in different genomes. The various substrate specificities among phosphotransferase systems in different genomes apparently reflect on differences in habitat, lifestyle, and nutrient sources.

Energy Metabolism↗
PubMed2003

Predicting gene expression levels from codon biases in alpha-proteobacterial genomes.

Predicted highly expressed (PHX) genes in five currently available high G+C complete alpha-proteobacterial genomes are analyzed. These include: the nitrogen-fixing plant symbionts Sinorhizobium meliloti (SINME) and Mesorhizobium loti (MESLO), the nonpathogenic aquatic bacterium Caulobacter crescentus (CAUCR), the plant pathogen Agrobacterium tumefaciens (AGRTU), and the mammalian pathogen Brucella melitensis (BRUME). Three of these genomes, SINME, AGRTU, and BRUME, contain multiple chromosomes or megaplasmids (>1 Mb length). PHX genes in these genomes are concentrated mainly in the major (largest) chromosome with few PHX genes found in the secondary chromosomes and megaplasmids. Tricarboxylic acid cycle and aerobic respiration genes are strongly PHX in all five genomes, whereas anaerobic pathways of glycolysis and fermentation are mostly not PHX. Only in MESLO (but not SINME) and BRUME are most glycolysis genes PHX. Many flagellar genes are PHX in MESLO and CAUCR, but mostly are not PHX in SINME and AGRTU. The nonmotile BRUME also carries many flagellar genes but these are generally not PHX and all but one are located in the second chromosome. CAUCR stands out among available prokaryotic genomes with 25 PHX TonB-dependent receptors. These are putatively involved in uptake of iron ions and other nonsoluble compounds.

Agrobacterium tumefaciens↗
PubMed2003

Genome comparisons and analysis.

As we enter the post-genomic era, with the accelerating availability of complete genome sequences, new theoretical approaches and new experimental techniques, our ability to dissect cellular processes at the molecular level continues to expand. Recent advances include the application of RNA interference methods to characterize loss-of-function phenotype genes in higher eukaryotes, comparative analysis of the human and mouse genome sequences, and methods for reconciling contradictory phylogenetic reconstructions. New developments feed into the increasingly rich content of databases such as the COG database. The next phase of research will be increasingly dominated by efforts to integrate the deluge of data into our understanding of biological systems.

Amino Acid Sequence↗
PubMed2002

Associations between human disease genes and overlapping gene groups and multiple amino acid runs.

Overlapping gene groups (OGGs) arise when exons of one gene are contained within the introns of another. Typically, the two overlapping genes are encoded on opposite DNA strands. OGGs are often associated with specific disease phenotypes. In this report, we identify genes with OGG architecture and genes encoding multiple long amino acid runs and examine their relations to diseases. OGGs appear to be susceptible to genomic rearrangements as happens commonly with the loci of the DiGeorge syndrome on human chromosome 22. We also examine the degree of conservation of OGGs between human and mouse. Our analyses suggest that (i) a high proportion of genes in OGG regions are disease-associated, (ii) genomic rearrangements are likely to occur within OGGs, possibly as a consequence of anomalous sequence features prevalent in these regions, and (iii) multiple amino acid runs are also frequently associated with pathologies.

Amino Acids↗
PubMed2002

Frequent oligonucleotide motifs in genomes of three streptococci.

Complete genomes of three closely related Gram-positive bacteria Streptococcus pyogenes, Streptococcus pneumoniae and Lactococcus lactis are analyzed for abundances of short DNA sequence motifs (frequent words). The character and extent of frequent words are strikingly different among these genomes. The frequent words of S.pneumoniae split into three categories: parts of the previously characterized RUP and BOX repetitive elements and a 24 bp tandem repeat in the gene SP1772. The most abundant frequent words of L.lactis are all related to the 13 bp motif, WWNTTACTGACRR or its inverted complement YYGTCAGTAANWW. Distributional analysis of this motif, which we called highly repetitive motif (HRM), indicates its possible dual role. Frequent occurrences immediately downstream of genes suggest a possible role in transcription termination whereas spacings of consecutive HRMs consistent with the DNA helical period are indicative of a protein-binding site. Two regions of the L.lactis genome feature an intriguing pattern of several periodically occurring HRMs separated by precisely 59 bp. In a striking contrast to S.pneumoniae and L.lactis, S.pyogenes contains hardly any frequent words.

Base Sequence↗
PubMed2002

Genes, pseudogenes, and Alu sequence organization across human chromosomes 21 and 22.

Human chromosomes 21 and 22 (mainly the q-arms) were the first complete parts of the human genome released. Our analysis of genes, pseudogenes (Psig), and Alu repeats across these chromosomes include the following findings: The number of gene structures containing untranslated exons exceeds 25%; the terminal exon tends to be the largest among exons, whereas, the initial intron tends to be the largest among introns; single-exon gene length is approximately the mean gene exon number times the mean internal exon length; processed Psig lengths are on average approximately the same as single-exon gene length; and the G+C content and length of genes are uncorrelated. The counts and distribution of genes, Psig, and Alu sequences and G+C variation are evaluated with respect to clusters and overdispersions. Other assessments concern comparisons of intergenic lengths, properties of Psig sequences, and correlations between Alu and Psig sequences.

Alu Elements↗
PubMed2002

Amino acid runs in eukaryotic proteomes and disease associations.

We present a comparative proteome analysis of the five complete eukaryotic genomes (human, Drosophila melanogaster, Caenorhabditis elegans, Saccharomyces cerevisiae, Arabidopsis thaliana), focusing on individual and multiple amino acid runs, charge and hydrophobic runs. We found that human proteins with multiple long runs are often associated with diseases; these include long glutamine runs that induce neurological disorders, various cancers, categories of leukemias (mostly involving chromosomal translocations), and an abundance of Ca(2 +) and K(+) channel proteins. Many human proteins with multiple runs function in development and/or transcription regulation and are Drosophila homeotic homologs. A large number of these proteins are expressed in the nervous system. More than 80% of Drosophila proteins with multiple runs seem to function in transcription regulation. The most frequent amino acid runs in Drosophila sequences occur for glutamine, alanine, and serine, whereas human sequences highlight glutamate, proline, and leucine. The most frequent runs in yeast are of serine, glutamine, and acidic residues. Compared with the other eukaryotic proteomes, amino acid runs are significantly more abundant in the fly. This finding might be interpreted in terms of innate differences in DNA-replication processes, repair mechanisms, DNA-modification systems, and mutational biases. There are striking differences in amino acid runs for glutamine, asparagine, and leucine among the five proteomes.

Animals↗
PubMed2002

Heterogeneity of genome and proteome content in bacteria, archaea, and eukaryotes.

Our analysis compares bacteria, archaea, and eukaryota with respect to a wide assortment of genome and proteome properties. These properties include ribosomal protein gene distributions, chaperone protein contrasts, major variation of transcription/translation factors, gene encoding pathways of energy metabolism, and predicted protein expression levels. Significant differences within and between the three domains of life include protein lengths, information processing procedures, many metabolic and lipid biosynthesis pathways, cellular controls, and regulatory proteins. Differences among genomes are influenced by lifestyle, habitat, physiology, energy sources, and other factors.

Amino Acids↗
PubMed2002

Correlations between Shine-Dalgarno sequences and gene features such as predicted expression levels and operon structures.

This work assesses relationships for 30 complete prokaryotic genomes between the presence of the Shine-Dalgarno (SD) sequence and other gene features, including expression levels, type of start codon, and distance between successive genes. A significant positive correlation of the presence of an SD sequence and the predicted expression level of a gene based on codon usage biases was ascertained, such that predicted highly expressed genes are more likely to possess a strong SD sequence than average genes. Genes with AUG start codons are more likely than genes with other start codons, GUG or UUG, to possess an SD sequence. Genes in close proximity to upstream genes on the same coding strand in most genomes are significantly higher in SD presence. In light of these results, we discuss the role of the SD sequence in translation initiation and its relationship with predicted gene expression levels and with operon structure in both bacterial and archaeal genomes.

Archaeal Proteins↗