Helical Chirality: a Link between Local Interactions and Global Topology in DNA

DNA supercoiling plays a major role in many cellular functions. The global DNA conformation is however intimately linked to local DNA-DNA interactions influencing both the physical properties and the biological functions of the supercoiled molecule. Juxtaposition of DNA double helices in ubiquitous crossover arrangements participates in multiple functions such as recombination, gene regulation and DNA packaging. However, little is currently known about how the structure and stability of direct DNA-DNA interactions influence the topological state of DNA. Here, a crystallographic analysis shows that due to the intrinsic helical chirality of DNA, crossovers of opposite handedness exhibit markedly different geometries. While right-handed crossovers are self-fitted by sequence-specific groove-backbone interaction and bridging Mg2+ sites, left-handed crossovers are juxtaposed by groove-groove interaction. Our previous calculations have shown that the different geometries result in differential stabilisation in solution, in the presence of divalent cations. The present study reveals that the various topological states of the cell are associated with different inter-segmental interactions. While the unstable left-handed crossovers are exclusively formed in negatively supercoiled DNA, stable right-handed crossovers constitute the local signature of an unusual topological state in the cell, such as the positively supercoiled or relaxed DNA. These findings not only provide a simple mechanism for locally sensing the DNA topology but also lead to the prediction that, due to their different tertiary intra-molecular interactions, supercoiled molecules of opposite signs must display markedly different physical properties. Sticky inter-segmental interactions in positively supercoiled or relaxed DNA are expected to greatly slow down the slithering dynamics of DNA. We therefore suggest that the intrinsic helical chirality of DNA may have oriented the early evolutionary choices for DNA topology

Patterns and Collective Behavior in Granular Media: Theoretical Concepts

Granular materials are ubiquitous in our daily lives. While they have been a subject of intensive engineering research for centuries, in the last decade granular matter attracted significant attention of physicists. Yet despite a major efforts by many groups, the theoretical description of granular systems remains largely a plethora of different, often contradicting concepts and approaches. Authors give an overview of various theoretical models emerged in the physics of granular matter, with the focus on the onset of collective behavior and pattern formation. Their aim is two-fold: to identify general principles common for granular systems and other complex non-equilibrium systems, and to elucidate important distinctions between collective behavior in granular and continuum pattern-forming systems.Comment: Submitted to Reviews of Modern Physics. Full text with figures (2Mb pdf) avaliable at http://mti.msd.anl.gov/AransonTsimringReview/aranson_tsimring.pdf Community responce is appreciated. Comments/suggestions send to [email protected]

Phylogenetic and Phyletic Studies of Informational Genes in Genomes Highlight Existence of a 4th Domain of Life Including Giant Viruses

The discovery of Mimivirus, with its very large genome content, made it possible to identify genes common to the three domains of life (Eukarya, Bacteria and Archaea) and to generate controversial phylogenomic trees congruent with that of ribosomal genes, branching Mimivirus at its root. Here we used sequences from metagenomic databases, Marseillevirus and three new viruses extending the Mimiviridae family to generate the phylogenetic trees of eight proteins involved in different steps of DNA processing. Compared to the three ribosomal defined domains, we report a single common origin for Nucleocytoplasmic Large DNA Viruses (NCLDV), DNA processing genes rooted between Archaea and Eukarya, with a topology congruent with that of the ribosomal tree. As for translation, we found in our new viruses, together with Mimivirus, five proteins rooted deeply in the eukaryotic clade. In addition, comparison of informational genes repertoire based on phyletic pattern analysis supports existence of a clade containing NCLDVs clearly distinct from that of Eukarya, Bacteria and Archaea. We hypothesize that the core genome of NCLDV is as ancient as the three currently accepted domains of life

Microtubules in Bacteria: Ancient Tubulins Build a Five-Protofilament Homolog of the Eukaryotic Cytoskeleton

Microtubules play crucial roles in cytokinesis, transport, and motility, and are therefore superb targets for anti-cancer drugs. All tubulins evolved from a common ancestor they share with the distantly related bacterial cell division protein FtsZ, but while eukaryotic tubulins evolved into highly conserved microtubule-forming heterodimers, bacterial FtsZ presumably continued to function as single homopolymeric protofilaments as it does today. Microtubules have not previously been found in bacteria, and we lack insight into their evolution from the tubulin/FtsZ ancestor. Using electron cryomicroscopy, here we show that the tubulin homologs BtubA and BtubB form microtubules in bacteria and suggest these be referred to as “bacterial microtubules” (bMTs). bMTs share important features with their eukaryotic counterparts, such as straight protofilaments and similar protofilament interactions. bMTs are composed of only five protofilaments, however, instead of the 13 typical in eukaryotes. These and other results suggest that rather than being derived from modern eukaryotic tubulin, BtubA and BtubB arose from early tubulin intermediates that formed small microtubules. Since we show that bacterial microtubules can be produced in abundance in vitro without chaperones, they should be useful tools for tubulin research and drug screening

Reduced stability of mRNA secondary structure near the translation-initiation site in dsDNA viruses

<p>Abstract</p> <p>Background</p> <p>Recent studies have demonstrated a selection pressure for reduced mRNA secondary-structure stability near the start codon of coding sequences. This selection pressure can be observed in bacteria, archaea, and eukaryotes, and is likely caused by the requirement of efficient translation initiation in cellular organism.</p> <p>Results</p> <p>Here, we surveyed the complete genomes of 650 dsDNA virus strains for signals of reduced stability of mRNA secondary structure near the start codon. Our analysis included viruses infecting eukaryotic, prokaryotic, and archaeic hosts. We found that many viruses showed evidence for reduced mRNA secondary-structure stability near the start codon. The effect was most pronounced in viruses infecting prokaryotes, but was also observed in viruses infecting eukaryotes and archaea. The reduction in stability generally increased with increasing genomic GC content. For bacteriophage, the reduction was correlated with a corresponding reduction of stability in the phage hosts.</p> <p>Conclusions</p> <p>We conclude that reduced stability of the mRNA secondary structure near the start codon is a common feature for dsDNA viruses, likely driven by the same selective pressures that cause it in cellular organisms.</p

Detection of Biochemical Pathways by Probabilistic Matching of Phyletic Vectors

A phyletic vector, also known as a phyletic (or phylogenetic) pattern, is a binary representation of the presences and absences of orthologous genes in different genomes. Joint occurrence of two or more genes in many genomes results in closely similar binary vectors representing these genes, and this similarity between gene vectors may be used as a measure of functional association between genes. Better understanding of quantitative properties of gene co-occurrences is needed for systematic studies of gene function and evolution. We used the probabilistic iterative algorithm Psi-square to find groups of similar phyletic vectors. An extended Psi-square algorithm, in which pseudocounts are implemented, shows better sensitivity in identifying proteins with known functional links than our earlier hierarchical clustering approach. At the same time, the specificity of inferring functional associations between genes in prokaryotic genomes is strongly dependent on the pathway: phyletic vectors of the genes involved in energy metabolism and in de novo biosynthesis of the essential precursors tend to be lumped together, whereas cellular modules involved in secretion, motility, assembly of cell surfaces, biosynthesis of some coenzymes, and utilization of secondary carbon sources tend to be identified with much greater specificity. It appears that the network of gene coinheritance in prokaryotes contains a giant connected component that encompasses most biosynthetic subsystems, along with a series of more independent modules involved in cell interaction with the environment

Mth10b, a Unique Member of the Sac10b Family, Does Not Bind Nucleic Acid

The Sac10b protein family is regarded as a group of nucleic acid-binding proteins that are highly conserved and widely distributed within archaea. All reported members of this family are basic proteins that exist as homodimers in solution and bind to DNA and/or RNA without apparent sequence specificity in vitro. Here, we reported a unique member of the family, Mth10b from Methanobacterium thermoautotrophicum ΔH, whose amino acid sequence shares high homology with other Sac10b family proteins. However, unlike those proteins, Mth10b is an acidic protein; its potential isoelectric point is only 4.56, which is inconsistent with the characteristics of a nucleic acid-binding protein. In this study, Mth10b was expressed in Escherichia coli and purified using a three-column chromatography purification procedure. Biochemical characterization indicated that Mth10b should be similar to typical Sac10b family proteins with respect to its secondary and tertiary structure and in its preferred oligomeric forms. However, an electrophoretic mobility shift analysis (EMSA) showed that neither DNA nor RNA bound to Mth10b in vitro, indicating that either Mth10b likely has a physiological function that is distinct from those of other Sac10b family members or nucleic acid-binding ability may not be a fundamental factor to the actual function of the Sac10b family

From essential to persistent genes: a functional approach to constructing synthetic life

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