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Anatoly Yambartsev, Michael A Perlin, Yevgeniy Kovchegov, Natalia Shulzhenko, Karina L Mine, Xiaoxi Dong, Andrey Morgun
BACKGROUND: Gene covariation networks are commonly used to study biological processes. The inference of gene covariation networks from observational data can be challenging, especially considering the large number of players involved and the small number of biological replicates available for analysis. RESULTS: We propose a new statistical method for estimating the number of erroneous edges in reconstructed networks that strongly enhances commonly used inference approaches...
October 13, 2016: Biology Direct
Itamar Sela, Yuri I Wolf, Eugene V Koonin
Bacteria and archaea typically possess small genomes that are tightly packed with protein-coding genes. The compactness of prokaryotic genomes is commonly perceived as evidence of adaptive genome streamlining caused by strong purifying selection in large microbial populations. In such populations, even the small cost incurred by nonfunctional DNA because of extra energy and time expenditure is thought to be sufficient for this extra genetic material to be eliminated by selection. However, contrary to the predictions of this model, there exists a consistent, positive correlation between the strength of selection at the protein sequence level, measured as the ratio of nonsynonymous to synonymous substitution rates, and microbial genome size...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
Jaime Iranzo, Eugene V Koonin, David Prangishvili, Mart Krupovic
: Archaea and particularly hyperthermophilic crenarchaea are hosts to many unusual viruses with diverse virion shapes and distinct gene compositions. As is typical of viruses in general, there are no universal genes in the archaeal virosphere. Therefore, to obtain a comprehensive picture of the evolutionary relationships between viruses, network analysis methods are more productive than traditional phylogenetic approaches. Here we present a comprehensive comparative analysis of genomes and proteomes from all currently known taxonomically classified and unclassified, cultivated and uncultivated archaeal viruses...
September 28, 2016: Journal of Virology
Eszter Tóth, Nóra Weinhardt, Petra Bencsura, Krisztina Huszár, Péter I Kulcsár, András Tálas, Elfrieda Fodor, Ervin Welker
BACKGROUND: Cpf1 nucleases have recently been repurposed for site-specific genome modification. Two members of the Cpf1 family, the AsCpf1 from Acidaminococcus sp. and the LbCpf1 from Lachnospiraceae bacterium were shown to induce higher indel frequencies than SpCas9 when examining four randomly-selected target sequences for each type of nuclease. Whether they are a real match for Cas9 nucleases, however, remains to be verified. RESULTS: Here, we used AsCpf1 and LbCpf1 to induce homology directed repair, either single strand annealing (SSA) or homologous recombination (HR), in N2a mouse neuroblastoma cells...
2016: Biology Direct
Eugene V Koonin
The wide spread of gene exchange and loss in the prokaryotic world has prompted the concept of 'lateral genomics' to the point of an outright denial of the relevance of phylogenetic trees for evolution. However, the pronounced coherence congruence of the topologies of numerous gene trees, particularly those for (nearly) universal genes, translates into the notion of a statistical tree of life (STOL), which reflects a central trend of vertical evolution. The STOL can be employed as a framework for reconstruction of the evolutionary processes in the prokaryotic world...
2016: F1000Research
Jaime Iranzo, Pere Puigbo, Alexander E Lobkovsky, Yuri I Wolf, Eugene V Koonin
Almost all cellular life forms are hosts to diverse genetic parasites with various levels of autonomy including plasmids, transposons and viruses. Theoretical modeling of the evolution of primordial replicators indicates that parasites ('cheaters') necessarily evolve in such systems and can be kept at bay primarily via compartmentalization. Given the (near) ubiquity, abundance and diversity of genetic parasites, the question becomes pertinent: are such parasites intrinsic to life? At least in prokaryotes, the persistence of parasites is linked to the rate of horizontal gene transfer (HGT)...
August 8, 2016: Genome Biology and Evolution
Prarthana Mohanraju, Kira S Makarova, Bernd Zetsche, Feng Zhang, Eugene V Koonin, John van der Oost
Adaptive immunity had been long thought of as an exclusive feature of animals. However, the discovery of the CRISPR-Cas defense system, present in almost half of prokaryotic genomes, proves otherwise. Because of the everlasting parasite-host arms race, CRISPR-Cas has rapidly evolved through horizontal transfer of complete loci or individual modules, resulting in extreme structural and functional diversity. CRISPR-Cas systems are divided into two distinct classes that each consist of three types and multiple subtypes...
August 5, 2016: Science
Jaime Iranzo, Mart Krupovic, Eugene V Koonin
UNLABELLED: Virus genomes are prone to extensive gene loss, gain, and exchange and share no universal genes. Therefore, in a broad-scale study of virus evolution, gene and genome network analyses can complement traditional phylogenetics. We performed an exhaustive comparative analysis of the genomes of double-stranded DNA (dsDNA) viruses by using the bipartite network approach and found a robust hierarchical modularity in the dsDNA virosphere. Bipartite networks consist of two classes of nodes, with nodes in one class, in this case genomes, being connected via nodes of the second class, in this case genes...
2016: MBio
Guilhem Faure, Aleksey Y Ogurtsov, Svetlana A Shabalina, Eugene V Koonin
Specific structures in mRNA modulate translation rate and thus can affect protein folding. Using the protein structures from two eukaryotes and three prokaryotes, we explore the connections between the protein compactness, inferred from solvent accessibility, and mRNA structure, inferred from mRNA folding energy (ΔG). In both prokaryotes and eukaryotes, the ΔG value of the most stable 30 nucleotide segment of the mRNA (ΔGmin) strongly, positively correlates with protein solvent accessibility. Thus, mRNAs containing exceptionally stable secondary structure elements typically encode compact proteins...
July 27, 2016: Nucleic Acids Research
Eugene V Koonin
The history of life is punctuated by evolutionary transitions which engender emergence of new levels of biological organization that involves selection acting at increasingly complex ensembles of biological entities. Major evolutionary transitions include the origin of prokaryotic and then eukaryotic cells, multicellular organisms and eusocial animals. All or nearly all cellular life forms are hosts to diverse selfish genetic elements with various levels of autonomy including plasmids, transposons and viruses...
August 19, 2016: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
Chris A Van Beneden, Harald Pietz, Robert D Kirkcaldy, Lisa M Koonin, Timothy M Uyeki, Alexandra M Oster, Deborah A Levy, Maleeka Glover, Matthew J Arduino, Toby L Merlin, David T Kuhar, Christine Kosmos, Beth P Bell
In response to the 2014-2016 Ebola virus disease (Ebola) epidemic in West Africa, CDC prepared for the potential introduction of Ebola into the United States. The immediate goals were to rapidly identify and isolate any cases of Ebola, prevent transmission, and promote timely treatment of affected patients. CDC's technical expertise and the collaboration of multiple partners in state, local, and municipal public health departments; health care facilities; emergency medical services; and U.S. government agencies were essential to the domestic preparedness and response to the Ebola epidemic and relied on longstanding partnerships...
2016: MMWR Supplements
Richard H Smith, Claus V Hallwirth, Michael Westerman, Nicola A Hetherington, Yu-Shan Tseng, Sylvain Cecchini, Tamas Virag, Mona-Larissa Ziegler, Igor B Rogozin, Eugene V Koonin, Mavis Agbandje-McKenna, Robert M Kotin, Ian E Alexander
Germline endogenous viral elements (EVEs) genetically preserve viral nucleotide sequences useful to the study of viral evolution, gene mutation, and the phylogenetic relationships among host organisms. Here, we describe a lineage-specific, adeno-associated virus (AAV)-derived endogenous viral element (mAAV-EVE1) found within the germline of numerous closely related marsupial species. Molecular screening of a marsupial DNA panel indicated that mAAV-EVE1 occurs specifically within the marsupial suborder Macropodiformes (present-day kangaroos, wallabies, and related macropodoids), to the exclusion of other Diprotodontian lineages...
2016: Scientific Reports
Omar O Abudayyeh, Jonathan S Gootenberg, Silvana Konermann, Julia Joung, Ian M Slaymaker, David B T Cox, Sergey Shmakov, Kira S Makarova, Ekaterina Semenova, Leonid Minakhin, Konstantin Severinov, Aviv Regev, Eric S Lander, Eugene V Koonin, Feng Zhang
The clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated genes (Cas) adaptive immune system defends microbes against foreign genetic elements via DNA or RNA-DNA interference. We characterize the class 2 type VI CRISPR-Cas effector C2c2 and demonstrate its RNA-guided ribonuclease function. C2c2 from the bacterium Leptotrichia shahii provides interference against RNA phage. In vitro biochemical analysis shows that C2c2 is guided by a single CRISPR RNA and can be programmed to cleave single-stranded RNA targets carrying complementary protospacers...
August 5, 2016: Science
Gayatri Ramakrishnan, Abha Jain, Nagasuma Chandra, Narayanaswamy Srinivasan
UNLABELLED: Evolutionary relationship between class III nucleotide cyclases and an uncharacterized set of bacterial proteins from Actinobacteria, Bacteroidetes and Proteobacteria has been recognized and analyzed. Detailed analyses of sequence and structural features resulted in the recognition of potential cyclase function conferring residues and presence of signature topological motif (βααββαβ) in the uncharacterized set of bacterial proteins. Lack of transmembrane domains and signal peptide cleavage sites is suggestive of their cytosolic subcellular localization...
2016: Biology Direct
Daria Lavysh, Maria Sokolova, Leonid Minakhin, Maria Yakunina, Tatjana Artamonova, Sergei Kozyavkin, Kira S Makarova, Eugene V Koonin, Konstantin Severinov
Bacteriophage AR9 and its close relative PBS1 have been extensively used to construct early Bacillus subtilis genetic maps. Here, we present the 251,042bp AR9 genome, a linear, terminally redundant double-stranded DNA containing deoxyuridine instead of thymine. Multiple AR9 genes are interrupted by non-coding sequences or sequences encoding putative endonucleases. We show that these sequences are group I and group II self-splicing introns. Eight AR9 proteins are homologous to fragments of bacterial RNA polymerase (RNAP) subunits β/β'...
August 2016: Virology
Kira S Makarova, Eugene V Koonin, Sonja-Verena Albers
Many surface structures in archaea including various types of pili and the archaellum (archaeal flagellum) are homologous to bacterial type IV pili systems (T4P). The T4P consist of multiple proteins, often with poorly conserved sequences, complicating their identification in sequenced genomes. Here we report a comprehensive census of T4P encoded in archaeal genomes using sensitive methods for protein sequence comparison. This analysis confidently identifies as T4P components about 5000 archaeal gene products, 56% of which are currently annotated as hypothetical in public databases...
2016: Frontiers in Microbiology
Alon Diament, Tamir Tuller
BACKGROUND: Ribosome profiling (or Ribo-seq) is currently the most popular methodology for studying translation; it has been employed in recent years to decipher various fundamental gene expression regulation aspects. The main promise of the approach is its ability to detect ribosome densities over an entire transcriptome in high resolution of single codons. Indeed, dozens of ribo-seq studies have included results related to local ribosome densities in different parts of the transcript; nevertheless, the performance of Ribo-seq has yet to be quantitatively evaluated and reported in a large-scale multi-organismal and multi-protocol study of currently available datasets...
2016: Biology Direct
Takashi Yamano, Hiroshi Nishimasu, Bernd Zetsche, Hisato Hirano, Ian M Slaymaker, Yinqing Li, Iana Fedorova, Takanori Nakane, Kira S Makarova, Eugene V Koonin, Ryuichiro Ishitani, Feng Zhang, Osamu Nureki
Cpf1 is an RNA-guided endonuclease of a type V CRISPR-Cas system that has been recently harnessed for genome editing. Here, we report the crystal structure of Acidaminococcus sp. Cpf1 (AsCpf1) in complex with the guide RNA and its target DNA at 2.8 Å resolution. AsCpf1 adopts a bilobed architecture, with the RNA-DNA heteroduplex bound inside the central channel. The structural comparison of AsCpf1 with Cas9, a type II CRISPR-Cas nuclease, reveals both striking similarity and major differences, thereby explaining their distinct functionalities...
May 5, 2016: Cell
Theodor O Diener
The discovery of the viroid in 1971, which initiated the third major expansion of the biosphere towards smaller living entities-after discovery of the "subvisual" microorganisms in 1675 and that of the "submicroscopic" viruses in 1892-has been officially endorsed by the International Committee on Virus Taxonomy as a new order called subviral agents.In 1989, I proposed that, based on their respective molecular properties, viroids are more plausible "living fossils" of the hypothetical RNA World (widely assumed to have existed prior to the evolution of DNA or proteins) than are intron-derived RNAs, which were, at that time, suggested as putative survivors...
2016: Biology Direct
Eugene V Koonin, Petro Starokadomskyy
The question whether or not "viruses are alive" has caused considerable debate over many years. Yet, the question is effectively without substance because the answer depends entirely on the definition of life or the state of "being alive" that is bound to be arbitrary. In contrast, the status of viruses among biological entities is readily defined within the replicator paradigm. All biological replicators form a continuum along the selfishness-cooperativity axis, from the completely selfish to fully cooperative forms...
October 2016: Studies in History and Philosophy of Biological and Biomedical Sciences
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