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Author: Jean Weissenbach (113)



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Aug
2017

Experimental validation of enzyme function is crucial for genome interpretation, but it remains challenging because it cannot be scaled up to accommodate the constant accumulation of genome sequences. We tackled this issue for the MetA and MetX enzyme families, phylogenetically unrelated families of acyl-L-homoserine transferases involved in L-methionine biosynthesis. Members of these families are prone to incorrect annotation because MetX and MetA enzymes are assumed to always use acetyl-CoA and succinyl-CoA, respectively.

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Aug
2017

One-carbon metabolism is an ubiquitous metabolic pathway that encompasses the reactions transferring formyl-, hydroxymethyl- and methyl-groups bound to tetrahydrofolate for the synthesis of purine nucleotides, thymidylate, methionine and dehydropantoate, the precursor of coenzyme A. An alternative cyclic pathway was designed that substitutes 4-hydroxy-2-oxobutanoic acid (HOB), a compound absent from known metabolism, for the amino acids serine and glycine as one-carbon donors. It involves two novel reactions, the transamination of l-homoserine and the transfer of a one-carbon unit from HOB to tetrahydrofolate releasing pyruvate as coproduct.

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Dec
1969

Chlordecone (Kepone®) is a synthetic organochlorine insecticide (C10Cl10O) used worldwide mostly during the 1970 and 1980s. Its intensive application in the French West Indies to control the banana black weevil Cosmopolites sordidus led to a massive environmental pollution. Persistence of chlordecone in soils and water for numerous decades even centuries causes global public health and socio-economic concerns.

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Nov
2016

[Microbiotes and metagenomics].

Med Sci (Paris) 2016 Nov 23;32(11):937-943. Epub 2016 Dec 23.
Jean Weissenbach, Abdelghani Sghir
Major technical advances were introduced in the study of microflora and microbial communities in the nineties. These are essentially analytical approaches conducted as frequently by brute force. What conclusions can be drawn from these analyses twenty years later? In terms of microbial compositions, monitoring and diagnosis, the results are impressive.

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Nov
2016

The rise of genomics.

C R Biol 2016 Jul-Aug;339(7-8):231-9. Epub 2016 Jun 2.
Jean Weissenbach
A brief history of the development of genomics is provided. Complete sequencing of genomes of uni- and multicellular organisms is based on important progress in sequencing and bioinformatics. Evolution of these methods is ongoing and has triggered an explosion in data production and analysis.

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Apr
2016

The biological carbon pump is the process by which CO2 is transformed to organic carbon via photosynthesis, exported through sinking particles, and finally sequestered in the deep ocean. While the intensity of the pump correlates with plankton community composition, the underlying ecosystem structure driving the process remains largely uncharacterized. Here we use environmental and metagenomic data gathered during the Tara Oceans expedition to improve our understanding of carbon export in the oligotrophic ocean.

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May
2015

Species interaction networks are shaped by abiotic and biotic factors. Here, as part of the Tara Oceans project, we studied the photic zone interactome using environmental factors and organismal abundance profiles and found that environmental factors are incomplete predictors of community structure. We found associations across plankton functional types and phylogenetic groups to be nonrandomly distributed on the network and driven by both local and global patterns.

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May
2015

Microbes are dominant drivers of biogeochemical processes, yet drawing a global picture of functional diversity, microbial community structure, and their ecological determinants remains a grand challenge. We analyzed 7.2 terabases of metagenomic data from 243 Tara Oceans samples from 68 locations in epipelagic and mesopelagic waters across the globe to generate an ocean microbial reference gene catalog with >40 million nonredundant, mostly novel sequences from viruses, prokaryotes, and picoeukaryotes.

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Jul
2015

To gain an in-depth insight into the diversity and the distribution of genes under the particular evolutionary pressure of an arsenic-rich acid mine drainage (AMD), the genes involved in bacterial arsenic detoxification (arsB, ACR3) and arsenite oxidation (aioA) were investigated in sediment from Carnoulès (France), in parallel to the diversity and global distribution of the metabolically active bacteria. The metabolically active bacteria were affiliated mainly to AMD specialists, i.e.

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Nov
2014

Microbial metabolism of plant polysaccharides is an important part of environmental carbon cycling, human nutrition, and industrial processes based on cellulosic bioconversion. Here we demonstrate a broadly applicable method to analyze how microbes catabolize plant polysaccharides that integrates carbohydrate-active enzyme (CAZyme) assays, RNA sequencing (RNA-seq), and anaerobic growth screening. We apply this method to study how the bacterium Clostridium phytofermentans ferments plant biomass components including glucans, mannans, xylans, galactans, pectins, and arabinans.

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Dec
1969

Expansive knowledge of bacterial metabolism has been gained from genome sequencing output, but the high proportion of genes lacking a proper functional annotation in a given genome still impedes the accurate prediction of the metabolism of a cell. To access to a more global view of the functioning of the soil bacterium Acinetobacter baylyi ADP1, we adopted a multi 'omics' approach. Application of RNA-seq transcriptomics and LC/MS-based metabolomics, along with the systematic phenotyping of the complete collection of single-gene deletion mutants of A.

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Aug
2014

Microbes hold the key to life. They hold the secrets to our past (as the descendants of the earliest forms of life) and the prospects for our future (as we mine their genes for solutions to some of the planet's most pressing problems, from global warming to antibiotic resistance). However, the piecemeal approach that has defined efforts to study microbial genetic diversity for over 20 years and in over 30,000 genome projects risks squandering that promise.

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Jan
2014

Millions of protein database entries are not assigned reliable functions, preventing the full understanding of chemical diversity in living organisms. Here, we describe an integrated strategy for the discovery of various enzymatic activities catalyzed within protein families of unknown or little known function. This approach relies on the definition of a generic reaction conserved within the family, high-throughput enzymatic screening on representatives, structural and modeling investigations and analysis of genomic and metabolic context.

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Aug
2013

Loss of sexual reproduction is considered an evolutionary dead end for metazoans, but bdelloid rotifers challenge this view as they appear to have persisted asexually for millions of years. Neither male sex organs nor meiosis have ever been observed in these microscopic animals: oocytes are formed through mitotic divisions, with no reduction of chromosome number and no indication of chromosome pairing. However, current evidence does not exclude that they may engage in sex on rare, cryptic occasions.

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Mar
2013

Red seaweeds are key components of coastal ecosystems and are economically important as food and as a source of gelling agents, but their genes and genomes have received little attention. Here we report the sequencing of the 105-Mbp genome of the florideophyte Chondrus crispus (Irish moss) and the annotation of the 9,606 genes. The genome features an unusual structure characterized by gene-dense regions surrounded by repeat-rich regions dominated by transposable elements.

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Dec
1969

High-quality annotation of microsporidian genomes is essential for understanding the biological processes that govern the development of these parasites. Here we present an improved structural annotation method using transcriptional DNA signals. We apply this method to re-annotate four previously annotated genomes, which allow us to detect annotation errors and identify a significant number of unpredicted genes.

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Aug
2012

Bananas (Musa spp.), including dessert and cooking types, are giant perennial monocotyledonous herbs of the order Zingiberales, a sister group to the well-studied Poales, which include cereals. Bananas are vital for food security in many tropical and subtropical countries and the most popular fruit in industrialized countries.

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Jun
2012

African Green Monkeys (AGM) are amongst the most frequently used nonhuman primate models in clinical and biomedical research, nevertheless only few genomic resources exist for this species. Such information would be essential for the development of dedicated new generation technologies in fundamental and pre-clinical research using this model, and would deliver new insights into primate evolution.
We have exhaustively sequenced an Expression Sequence Tag (EST) library made from a pool of Peripheral Blood Mononuclear Cells from sixteen Chlorocebus sabaeus monkeys.

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May
2012

Despite the current wealth of sequencing data, one-third of all biochemically characterized metabolic enzymes lack a corresponding gene or protein sequence, and as such can be considered orphan enzymes. They represent a major gap between our molecular and biochemical knowledge, and consequently are not amenable to modern systemic analyses. As 555 of these orphan enzymes have metabolic pathway neighbours, we developed a global framework that utilizes the pathway and (meta)genomic neighbour information to assign candidate sequences to orphan enzymes.

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Feb
2012

Polyploidization is an important process in the evolution of eukaryotic genomes, but ensuing molecular mechanisms remain to be clarified. Autopolyploidization or whole-genome duplication events frequently are resolved in resulting lineages by the loss of single genes from most duplicated pairs, causing transient gene dosage imbalance and accelerating speciation through meiotic infertility. Allopolyploidization or formation of interspecies hybrids raises the problem of genetic incompatibility (Bateson-Dobzhansky-Muller effect) and may be resolved by the accumulation of mutational changes in resulting lineages.

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Dec
1969

Taking advantage of the massive genome sequencing effort made on thermophilic prokaryotes, thermal adaptation has been extensively studied by analysing amino acid replacements and codon usage in these unicellular organisms. In most cases, adaptation to thermophily is associated with greater residue hydrophobicity and more charged residues. Both of these characteristics are positively correlated with the optimal growth temperature of prokaryotes.

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Nov
2011

The Medicago genome provides insight into the evolution of rhizobial symbioses.

Nature 2011 Nov 16;480(7378):520-4. Epub 2011 Nov 16.
Nevin D Young, Frédéric Debellé, Giles E D Oldroyd, Rene Geurts, Steven B Cannon, Michael K Udvardi, Vagner A Benedito, Klaus F X Mayer, Jérôme Gouzy, Heiko Schoof, Yves Van de Peer, Sebastian Proost, Douglas R Cook, Blake C Meyers, Manuel Spannagl, Foo Cheung, Stéphane De Mita, Vivek Krishnakumar, Heidrun Gundlach, Shiguo Zhou, Joann Mudge, Arvind K Bharti, Jeremy D Murray, Marina A Naoumkina, Benjamin Rosen, Kevin A T Silverstein, Haibao Tang, Stephane Rombauts, Patrick X Zhao, Peng Zhou, Valérie Barbe, Philippe Bardou, Michael Bechner, Arnaud Bellec, Anne Berger, Hélène Bergès, Shelby Bidwell, Ton Bisseling, Nathalie Choisne, Arnaud Couloux, Roxanne Denny, Shweta Deshpande, Xinbin Dai, Jeff J Doyle, Anne-Marie Dudez, Andrew D Farmer, Stéphanie Fouteau, Carolien Franken, Chrystel Gibelin, John Gish, Steven Goldstein, Alvaro J González, Pamela J Green, Asis Hallab, Marijke Hartog, Axin Hua, Sean J Humphray, Dong-Hoon Jeong, Yi Jing, Anika Jöcker, Steve M Kenton, Dong-Jin Kim, Kathrin Klee, Hongshing Lai, Chunting Lang, Shaoping Lin, Simone L Macmil, Ghislaine Magdelenat, Lucy Matthews, Jamison McCorrison, Erin L Monaghan, Jeong-Hwan Mun, Fares Z Najar, Christine Nicholson, Céline Noirot, Majesta O'Bleness, Charles R Paule, Julie Poulain, Florent Prion, Baifang Qin, Chunmei Qu, Ernest F Retzel, Claire Riddle, Erika Sallet, Sylvie Samain, Nicolas Samson, Iryna Sanders, Olivier Saurat, Claude Scarpelli, Thomas Schiex, Béatrice Segurens, Andrew J Severin, D Janine Sherrier, Ruihua Shi, Sarah Sims, Susan R Singer, Senjuti Sinharoy, Lieven Sterck, Agnès Viollet, Bing-Bing Wang, Keqin Wang, Mingyi Wang, Xiaohong Wang, Jens Warfsmann, Jean Weissenbach, Doug D White, Jim D White, Graham B Wiley, Patrick Wincker, Yanbo Xing, Limei Yang, Ziyun Yao, Fu Ying, Jixian Zhai, Liping Zhou, Antoine Zuber, Jean Dénarié, Richard A Dixon, Gregory D May, David C Schwartz, Jane Rogers, Francis Quétier, Christopher D Town, Bruce A Roe
Legumes (Fabaceae or Leguminosae) are unique among cultivated plants for their ability to carry out endosymbiotic nitrogen fixation with rhizobial bacteria, a process that takes place in a specialized structure known as the nodule. Legumes belong to one of the two main groups of eurosids, the Fabidae, which includes most species capable of endosymbiotic nitrogen fixation. Legumes comprise several evolutionary lineages derived from a common ancestor 60 million years ago (Myr ago).

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Oct
2011

The structure, robustness, and dynamics of ocean plankton ecosystems remain poorly understood due to sampling, analysis, and computational limitations. The Tara Oceans consortium organizes expeditions to help fill this gap at the global level.

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Dec
1969

Ramlibacter tataouinensis TTB310(T) (strain TTB310), a betaproteobacterium isolated from a semi-arid region of South Tunisia (Tataouine), is characterized by the presence of both spherical and rod-shaped cells in pure culture. Cell division of strain TTB310 occurs by the binary fission of spherical "cyst-like" cells ("cyst-cyst" division). The rod-shaped cells formed at the periphery of a colony (consisting mainly of cysts) are highly motile and colonize a new environment, where they form a new colony by reversion to cyst-like cells.

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Sep
2011

Streptomyces cattleya, a producer of the antibiotics thienamycin and cephamycin C, is one of the rare bacteria known to synthesize fluorinated metabolites. The genome consists of two linear replicons. The genes involved in fluorine metabolism and in the biosynthesis of the antibiotic thienamycin were mapped on both replicons.

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Oct
2011

The human metagenome: our other genome?

Hum Mol Genet 2011 Oct 12;20(R2):R142-8. Epub 2011 Aug 12.
Thomas Brüls, Jean Weissenbach
For about a decade, the human microbiota has been investigated using molecular procedures that are now systematized via metagenomics. Several large scale studies are underway with the goal of establishing a set of reference data, such as catalogues of genes, microbial species and complete genome sequences of strains colonizing the various body sites. A first series of conclusions can be drawn from this 'natural history' approach that will also lay the ground for further studies aiming at understanding--in an ecological perspective--the mechanisms ensuring stable operation of the microbiota in healthy individuals, and how changes in its composition (dysbiosis) may result in diseases.

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Dec
1969

Bacteria are key components in all ecosystems. However, our knowledge of bacterial metabolism is based solely on the study of cultivated organisms which represent just a tiny fraction of microbial diversity. To access new enzymatic reactions and new or alternative pathways, we investigated bacterial metabolism through analyses of uncultivated bacterial consortia.

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Aug
2011

The exponential increase in genome sequencing output has led to the accumulation of thousands of predicted genes lacking a proper functional annotation. Among this mass of hypothetical proteins, enzymes catalyzing new reactions or using novel ways to catalyze already known reactions might still wait to be identified. Here, we provide a structural and biochemical characterization of the 3-keto-5-aminohexanoate cleavage enzyme (Kce), an enzymatic activity long known as being involved in the anaerobic fermentation of lysine but whose catalytic mechanism has remained elusive so far.

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Nov
2011

By their metabolic activities, microorganisms have a crucial role in the biogeochemical cycles of elements. The complete understanding of these processes requires, however, the deciphering of both the structure and the function, including synecologic interactions, of microbial communities. Using a metagenomic approach, we demonstrated here that an acid mine drainage highly contaminated with arsenic is dominated by seven bacterial strains whose genomes were reconstructed.

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May
2011

Enterotypes of the human gut microbiome.

Nature 2011 May 20;473(7346):174-80. Epub 2011 Apr 20.
Manimozhiyan Arumugam, Jeroen Raes, Eric Pelletier, Denis Le Paslier, Takuji Yamada, Daniel R Mende, Gabriel R Fernandes, Julien Tap, Thomas Bruls, Jean-Michel Batto, Marcelo Bertalan, Natalia Borruel, Francesc Casellas, Leyden Fernandez, Laurent Gautier, Torben Hansen, Masahira Hattori, Tetsuya Hayashi, Michiel Kleerebezem, Ken Kurokawa, Marion Leclerc, Florence Levenez, Chaysavanh Manichanh, H Bjørn Nielsen, Trine Nielsen, Nicolas Pons, Julie Poulain, Junjie Qin, Thomas Sicheritz-Ponten, Sebastian Tims, David Torrents, Edgardo Ugarte, Erwin G Zoetendal, Jun Wang, Francisco Guarner, Oluf Pedersen, Willem M de Vos, Søren Brunak, Joel Doré, , María Antolín, François Artiguenave, Hervé M Blottiere, Mathieu Almeida, Christian Brechot, Carlos Cara, Christian Chervaux, Antonella Cultrone, Christine Delorme, Gérard Denariaz, Rozenn Dervyn, Konrad U Foerstner, Carsten Friss, Maarten van de Guchte, Eric Guedon, Florence Haimet, Wolfgang Huber, Johan van Hylckama-Vlieg, Alexandre Jamet, Catherine Juste, Ghalia Kaci, Jan Knol, Omar Lakhdari, Severine Layec, Karine Le Roux, Emmanuelle Maguin, Alexandre Mérieux, Raquel Melo Minardi, Christine M'rini, Jean Muller, Raish Oozeer, Julian Parkhill, Pierre Renault, Maria Rescigno, Nicolas Sanchez, Shinichi Sunagawa, Antonio Torrejon, Keith Turner, Gaetana Vandemeulebrouck, Encarna Varela, Yohanan Winogradsky, Georg Zeller, Jean Weissenbach, S Dusko Ehrlich, Peer Bork
Our knowledge of species and functional composition of the human gut microbiome is rapidly increasing, but it is still based on very few cohorts and little is known about variation across the world. By combining 22 newly sequenced faecal metagenomes of individuals from four countries with previously published data sets, here we identify three robust clusters (referred to as enterotypes hereafter) that are not nation or continent specific. We also confirmed the enterotypes in two published, larger cohorts, indicating that intestinal microbiota variation is generally stratified, not continuous.

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Dec
2010

Genomes of animals as different as sponges and humans show conservation of global architecture. Here we show that multiple genomic features including transposon diversity, developmental gene repertoire, physical gene order, and intron-exon organization are shattered in the tunicate Oikopleura, belonging to the sister group of vertebrates and retaining chordate morphology. Ancestral architecture of animal genomes can be deeply modified and may therefore be largely nonadaptive.

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Feb
2011

To gain molecular insight into kidney function, we performed a high-resolution quantitative analysis of gene expression in glomeruli and nine different nephron segments dissected from mouse kidney using Serial Analysis of Gene Expression (SAGE). We also developed dedicated bioinformatics tools and databases to annotate mRNA tags as transcripts. Over 800,000 mRNA SAGE tags were sequenced corresponding to >20,000 different mRNA tags present at least twice in at least one library.

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Nov
2010

Alvinella pompejana is a representative of Annelids, a key phylum for evo-devo studies that is still poorly studied at the sequence level. A. pompejana inhabits deep-sea hydrothermal vents and is currently known as one of the most thermotolerant Eukaryotes in marine environments, withstanding the largest known chemical and thermal ranges (from 5 to 105°C).

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Oct
2010

Clostridium sticklandii belongs to a cluster of non-pathogenic proteolytic clostridia which utilize amino acids as carbon and energy sources. Isolated by T.C.

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Dec
1969

Diatoms represent the predominant group of eukaryotic phytoplankton in the oceans and are responsible for around 20% of global photosynthesis. Two whole genome sequences are now available. Notwithstanding, our knowledge of diatom biology remains limited because only around half of their genes can be ascribed a function based onhomology-based methods.

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Nov
2010

Autosomal dominant hypercholesterolemia (ADH) is characterized by isolated increase in plasmatic low-density lipoprotein (LDL) cholesterol levels associated with high risk of premature cardiovascular disease. Mutations in LDLR, APOB, and PCSK9 genes have been shown to cause ADH. We now report further genetic heterogeneity of ADH through the study of a large French family in which the involvement of these three genes was excluded.

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Mar
2010

Only three biological pathways are known to produce oxygen: photosynthesis, chlorate respiration and the detoxification of reactive oxygen species. Here we present evidence for a fourth pathway, possibly of considerable geochemical and evolutionary importance. The pathway was discovered after metagenomic sequencing of an enrichment culture that couples anaerobic oxidation of methane with the reduction of nitrite to dinitrogen.

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Feb
2010

Bacteria of the Thiomonas genus are ubiquitous in extreme environments, such as arsenic-rich acid mine drainage (AMD). The genome of one of these strains, Thiomonas sp. 3As, was sequenced, annotated, and examined, revealing specific adaptations allowing this bacterium to survive and grow in its highly toxic environment.

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Aug
2010

A culture-independent molecular phylogenetic approach was used to study prokaryotic diversity in an anoxic activated sludge from a municipal wastewater treatment plant. Two 16S rRNA gene libraries were constructed using total genomic DNA and amplified by polymerase chain reaction using primers specific for archaeal or bacterial domains. Phylogenetic analysis of 132 and 249 almost full-length 16S rRNA genes for Archaea and Bacteria, respectively, was done using the ARB software package.

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Oct
2009

Information produced by the annotation of an 'average bacterial genome' can be separated into three parts. One-third represents what we know, another third what we think we know, and the last third what we know we do not know. Knowledge of metabolism is also described by this three thirds rule.

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Oct
2009

Our knowledge of yeast genomes remains largely dominated by the extensive studies on Saccharomyces cerevisiae and the consequences of its ancestral duplication, leaving the evolution of the entire class of hemiascomycetes only partly explored. We concentrate here on five species of Saccharomycetaceae, a large subdivision of hemiascomycetes, that we call "protoploid" because they diverged from the S. cerevisiae lineage prior to its genome duplication.

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Dec
1969

Methylotrophy describes the ability of organisms to grow on reduced organic compounds without carbon-carbon bonds. The genomes of two pink-pigmented facultative methylotrophic bacteria of the Alpha-proteobacterial genus Methylobacterium, the reference species Methylobacterium extorquens strain AM1 and the dichloromethane-degrading strain DM4, were compared.
The 6.

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May
2009

For the ornithine fermentation pathway, described more than 70 years ago, genetic and biochemical information are still incomplete. We present here the experimental identification of the last four missing genes of this metabolic pathway. They encode L-ornithine racemase, (2R,4S)-2,4-diaminopentanoate dehydrogenase, and the two subunits of 2-amino-4-ketopentanoate thiolase.

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Jun
2009

The microbial consortium involved in anaerobic digestion has not yet been precisely characterized and this process remains a 'black box' with limited efficiency. In this study, seven anaerobic sludge digesters were selected based on technology, type of sludge, process and water quality. The prokaryotic community of these digesters was examined by constructing and analysing a total of 9890 16S rRNA gene clones.

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Nov
2008

Syncytin-2 is an envelope gene from the human endogenous retrovirus FRD (HERV-FRD) co-opted by an ancestral primate host, conserved in evolution over >40 Myr, specifically expressed in the placenta, and with a cell-cell fusogenic activity likely contributing to placenta morphogenesis. Here, using the GeneBridge4 human/Chinese hamster radiation hybrid panel, we mapped and identified the human receptor for syncytin-2. This receptor-namely Major Facilitator Superfamily Domain Containing 2 (MFSD2)-belongs to a large family of presumptive carbohydrate transporters with 10-12 membrane-spanning domains, is located at chromosomal position 1p34.

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