A highly conserved family of inactivated archaeal B family DNA polymerases

<p>Abstract</p> <p>A widespread and highly conserved family of apparently inactivated derivatives of archaeal B-family DNA polymerases is described. Phylogenetic analysis shows that the inactivated forms comprise a distinct clade among archaeal B-family polymerases and that, within this clade, Euryarchaea and Crenarchaea are clearly separated from each other and from a small group of bacterial homologs. These findings are compatible with an ancient duplication of the DNA polymerase gene followed by inactivation and parallel loss in some of the lineages although contribution of horizontal gene transfer cannot be ruled out. The inactivated derivative of the archaeal DNA polymerase could form a complex with the active paralog and play a structural role in DNA replication.</p> <p>Reviewers</p> <p>This article was reviewed by Purificacion Lopez-Garcia and Chris Ponting. For the full reviews, please go to the Reviewers' Reports section.</p

Evolution of DNA polymerases: an inactivated polymerase-exonuclease module in Pol ε and a chimeric origin of eukaryotic polymerases from two classes of archaeal ancestors

Background: Evolution of DNA polymerases, the key enzymes of DNA replication and repair, is central to any reconstruction of the history of cellular life. However, the details of the evolutionary relationships between DNA polymerases of archaea and eukaryotes remain unresolved. Results: We performed a comparative analysis of archaeal, eukaryotic, and bacterial B-family DNA polymerases, which are the main replicative polymerases in archaea and eukaryotes, combined with an analysis of domain architectures. Surprisingly, we found that eukaryotic Polymerase ε consists of two tandem exonuclease-polymerase modules, the active N-terminal module and a C-terminal module in which both enzymatic domains are inactivated. The two modules are only distantly related to each other, an observation that suggests the possibility that Pol ε evolved as a result of insertion and subsequent inactivation of a distinct polymerase, possibly, of bacterial descent, upstream of the C-terminal Zn-fingers, rather than by tandem duplication. The presence of an inactivated exonuclease-polymerase module in Pol ε parallels a similar inactivation of both enzymatic domains in a distinct family of archaeal B-family polymerases. The results of phylogenetic analysis indicate that eukaryotic B-family polymerases, most likely, originate from two distantly related archaeal B-family polymerases, one form giving rise to Pol ε, and the other one to the common ancestor of Pol α, Pol δ, and Pol ζ. The C-terminal Zn-fingers that are present in all eukaryotic B-family polymerases, unexpectedly, are homologous to the Zn-finger of archaeal D-family DNA polymerases that are otherwise unrelated to the B family. The Zn-finger of Polε shows a markedly greater similarity to the counterpart in archaeal PolD than the Zn-fingers of other eukaryotic B-family polymerases. Conclusion: Evolution of eukaryotic DNA polymerases seems to have involved previously unnoticed complex events. We hypothesize that the archaeal ancestor of eukaryotes encoded three DNA polymerases, namely, two distinct B-family polymerases and a D-family polymerase all of which contributed to the evolution of the eukaryotic replication machinery. The Zn-finger might have been acquired from PolD by the B-family form that gave rise to Pol ε prior to or in the course of eukaryogenesis, and subsequently, was captured by the ancestor of the other B-family eukaryotic polymerases. The inactivated polymerase-exonuclease module of Pol ε might have evolved by fusion with a distinct polymerase, rather than by duplication of the active module of Pol ε, and is likely to play an important role in the assembly of eukaryotic replication and repair complexes. Reviewers: This article was reviewed by Patrick Forterre, Arcady Mushegian, and Chris Ponting. For the full reviews, pleas

Psychopatological symptomatics in patients with alcoholic psychosis at the stationary treatment stage in the emergency department of narcological care

The paper presents the results of a psychopathological study of alcoholic patients undergoing treatment in the emergency department of narcology for alcoholic psychosis. The analysis of the socio-demographic characteristics of patients, their narcological profile was carried out. Revealed the clinical and dynamic characteristics of the staging of the psychotic process.В работе представлены результаты психопатологического исследования больных алкоголизмом, проходящих лечение в отделении неотложной наркологии по поводу алкогольного психоза. Проведен анализ социально-демографических характеристик пациентов, их наркологический профиль. Выявлены клинико-динамические характеристики стадийности психотического процесс

Elite opinion and foreign policy in post-communist Russia

Russian elite opinion on matters of foreign policy may be classified as ‘Liberal Westerniser’, ‘Pragmatic Nationalist’ and ‘Fundamentalist Nationalist’, terms that reflect longstanding debates about the country’s relationship with the outside world. An analysis of press statements and election manifestoes together with a programme of elite interviews between 2004 and 2006 suggests a clustering of opinion on a series of strategic issues. Liberal Westernisers seek the closest possible relationship with Europe, and favour eventual membership of the EU and NATO. Pragmatic Nationalists are more inclined to favour practical co-operation, and do not assume an identity of values or interests with the Western countries. Fundamentalist Nationalists place more emphasis on the other former Soviet republics, and on Asia as much as Europe, and see the West as a threat to Russian values as well as to its state interests. Each of these positions, in turn, draws on an identifiable set of domestic constituencies: Liberal Westernisers on the promarket political parties, Pragmatic Nationalists on the presidential administration and defence and security ministries, and Fundamentalist Nationalists on the Orthodox Church and Communists

Mycoplasma hyopneumoniae Transcription Unit Organization: Genome Survey and Prediction

Mycoplasma hyopneumoniae is associated with swine respiratory diseases. Although gene organization and regulation are well known in many prokaryotic organisms, knowledge on mycoplasma is limited. This study performed a comparative analysis of three strains of M. hyopneumoniae (7448, J and 232), with a focus on genome organization and gene comparison for open read frame (ORF) cluster (OC) identification. An in silico analysis of gene organization demonstrated 117 OCs and 34 single ORFs in M. hyopneumoniae 7448 and J, while 116 OCs and 36 single ORFs were identified in M. hyopneumoniae 232. Genomic comparison revealed high synteny and conservation of gene order between the OCs defined for 7448 and J strains as well as for 7448 and 232 strains. Twenty-one OCs were chosen and experimentally confirmed by reverse transcription–PCR from M. hyopneumoniae 7448 genome, validating our prediction. A subset of the ORFs within an OC could be independently transcribed due to the presence of internal promoters. Our results suggest that transcription occurs in ‘run-on’ from an upstream promoter in M. hyopneumoniae, thus forming large ORF clusters (from 2 to 29 ORFs in the same orientation) and indicating a complex transcriptional organization

Hypermutable Non-Synonymous Sites Are under Stronger Negative Selection

Mutation rate varies greatly between nucleotide sites of the human genome and depends both on the global genomic location and the local sequence context of a site. In particular, CpG context elevates the mutation rate by an order of magnitude. Mutations also vary widely in their effect on the molecular function, phenotype, and fitness. Independence of the probability of occurrence of a new mutation's effect has been a fundamental premise in genetics. However, highly mutable contexts may be preserved by negative selection at important sites but destroyed by mutation at sites under no selection. Thus, there may be a positive correlation between the rate of mutations at a nucleotide site and the magnitude of their effect on fitness. We studied the impact of CpG context on the rate of human–chimpanzee divergence and on intrahuman nucleotide diversity at non-synonymous coding sites. We compared nucleotides that occupy identical positions within codons of identical amino acids and only differ by being within versus outside CpG context. Nucleotides within CpG context are under a stronger negative selection, as revealed by their lower, proportionally to the mutation rate, rate of evolution and nucleotide diversity. In particular, the probability of fixation of a non-synonymous transition at a CpG site is two times lower than at a CpG site. Thus, sites with different mutation rates are not necessarily selectively equivalent. This suggests that the mutation rate may complement sequence conservation as a characteristic predictive of functional importance of nucleotide sites

Study of the stochastic clustering on the refractory material surface under the effect of plasma load in the PLM device

Tungsten plates were tested in stationary helium discharges in the PLM device. The duration of discharges in the PLM reached 200 minutes. A distinctive feature of this device is the stationary plasma confinement, which is advantageous for testing fusion materials, including materials of the divertor and first wall of a fusion reactor. During plasma irradiation in the PLM, the thermal load on the surface of the tested plates was more than 1 MW/m(2). The temperature of the tested plates amounted to 1000 degrees C and more. Stochastic nanostructures with dimensions of the structural elements of less than 50 nm, including fuzz-type structures, were observed on the processed surfaces of the samples

Sm/Lsm Genes Provide a Glimpse into the Early Evolution of the Spliceosome

The spliceosome, a sophisticated molecular machine involved in the removal of intervening sequences from the coding sections of eukaryotic genes, appeared and subsequently evolved rapidly during the early stages of eukaryotic evolution. The last eukaryotic common ancestor (LECA) had both complex spliceosomal machinery and some spliceosomal introns, yet little is known about the early stages of evolution of the spliceosomal apparatus. The Sm/Lsm family of proteins has been suggested as one of the earliest components of the emerging spliceosome and hence provides a first in-depth glimpse into the evolving spliceosomal apparatus. An analysis of 335 Sm and Sm-like genes from 80 species across all three kingdoms of life reveals two significant observations. First, the eukaryotic Sm/Lsm family underwent two rapid waves of duplication with subsequent divergence resulting in 14 distinct genes. Each wave resulted in a more sophisticated spliceosome, reflecting a possible jump in the complexity of the evolving eukaryotic cell. Second, an unusually high degree of conservation in intron positions is observed within individual orthologous Sm/Lsm genes and between some of the Sm/Lsm paralogs. This suggests that functional spliceosomal introns existed before the emergence of the complete Sm/Lsm family of proteins; hence, spliceosomal machinery with considerably fewer components than today's spliceosome was already functional