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Chan C.-M.,University of Hong Kong | Danchin A.,AMAbiotics SAS | Marliere P.,Genoscope Center National Of Sequencage | Sekowska A.,AMAbiotics SAS
Environmental Microbiology | Year: 2014

Metabolism is prone to produce analogs of essential building blocks in the cell (here named paralogous metabolism). The variants result from lack of absolute accuracy in enzyme-templated reactions as well as from molecular aging. If variants were left to accumulate, the earth would be covered by chemical waste. The way bacteria cope with this situation is essentially unexplored. To gain a comprehensive understanding of Bacillus subtilis sulphur paralogous metabolism, we used expression profiling with DNA arrays to investigate the changes in gene expression in the presence of S-methyl-cysteine (SMeC) and its close analog, methionine, as sole sulphur source. Altogether, more than 200 genes whose relative strength of induction was significantly different depending on the sulphur source used were identified. This allowed us to pinpoint operon ytmItcyJKLMNytmO_ytnIJ_rbfK_ytnLM as controlling the pathway cycling SMeC directly to cysteine, without requiring sulphur oxygenation. Combining genetic and physiological experiments, we deciphered the corresponding pathway that begins with protection of the metabolite by acetylation. Oxygenation of the methyl group then follows, and after deprotection (deacetylation), N-formyl cysteine is produced. This molecule is deformylated by the second deformylase present in B.subtilisDefB, yielding cysteine. This pathway appears to be present in plant-associated microbes. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd. Source


Davis E.E.,Duke University | Zhang Q.,University of Pennsylvania | Liu Q.,University of Pennsylvania | Diplas B.H.,Duke University | And 46 more authors.
Nature Genetics | Year: 2011

Ciliary dysfunction leads to a broad range of overlapping phenotypes, collectively termed ciliopathies. This grouping is underscored by genetic overlap, where causal genes can also contribute modifier alleles to clinically distinct disorders. Here we show that mutations in TTC21B, which encodes the retrograde intraflagellar transport protein IFT139, cause both isolated nephronophthisis and syndromic Jeune asphyxiating thoracic dystrophy. Moreover, although resequencing of TTC21B in a large, clinically diverse ciliopathy cohort and matched controls showed a similar frequency of rare changes, in vivo and in vitro evaluations showed a significant enrichment of pathogenic alleles in cases (P < 0.003), suggesting that TTC21B contributes pathogenic alleles to ∼5% of ciliopathy cases. Our data illustrate how genetic lesions can be both causally associated with diverse ciliopathies and interact in trans with other disease-causing genes and highlight how saturated resequencing followed by functional analysis of all variants informs the genetic architecture of inherited disorders. © 2011 Nature America, Inc. All rights reserved. Source


Gangloff B.,CNRS Chize Center for Biological Studies | Zino F.,Freiras Associacao Para A Conservacao e Proteccao da Natureza | Shirihai H.,c o Ausserdorfstrasse 6 | Gonzalez-Solis J.,University of Barcelona | And 3 more authors.
Molecular Ecology | Year: 2013

Macaronesia (north-east Atlantic archipelagos) has been host to complex patterns of colonization and differentiation in many groups of organisms including seabirds such as gadfly petrels (genus Pterodroma). Considering the subspecies of widely distributed soft-plumaged petrel for many years, the taxonomic status of the three gadfly petrel taxa breeding in Macaronesia is not yet settled, some authors advocating the presence of three, two or one species. These birds have already been the subject of genetic studies with only one mtDNA gene and relatively modest sample sizes. In this study, using a total of five genes (two mitochondrial genes and three nuclear introns), we investigated the population and phylogeographical histories of petrel populations breeding on Madeira and Cape Verde archipelagos. Despite confirming complete lineage sorting with mtDNA, analyses with nucDNA failed to reveal any population structuring and Isolation with Migration analysis revealed the absence of gene flow during the differentiation process of these populations. It appears that the three populations diverged in the late Pleistocene in the last 150 000 years, that is 10 times more recently than previous estimates based solely on one mtDNA gene. Finally, our results suggest that the Madeira petrel population is ancestral rather than that from Cape Verde. This study strongly advocates the use of nuclear loci in addition to mtDNA in demographical and phylogeographical history studies. © 2012 Blackwell Publishing Ltd. Source


Silberfeld T.,University Pierre and Marie Curie | Leigh J.W.,University Paris Diderot | Verbruggen H.,Ghent University | Cruaud C.,Genoscope Center National Of Sequencage | And 2 more authors.
Molecular Phylogenetics and Evolution | Year: 2010

The most conspicuous feature in previous phaeophycean phylogenies is a large polytomy known as the brown algal crown radiation (BACR). The BACR encompasses 10 out of the 17 currently recognized brown algal orders. A recent study has been able to resolve a few nodes of the BACR, suggesting that it may be a soft polytomy caused by a lack of signal in molecular markers. The present work aims to refine relationships within the BACR and investigate the nature and timeframe of the diversification in question using a dual approach. A multi-marker phylogeny of the brown algae was built from 10 mitochondrial, plastid and nuclear loci (>10,000 nt) of 72 phaeophycean taxa, resulting in trees with well-resolved inter-ordinal relationships within the BACR. Using Bayesian relaxed molecular clock analysis, it is shown that the BACR is likely to represent a gradual diversification spanning most of the Lower Cretaceous rather than a sudden radiation. Non-molecular characters classically used in ordinal delimitation were mapped on the molecular topology to study their evolutionary history. © 2010 Elsevier Inc. All rights reserved. Source


Heilig R.,Genoscope Center National Of Sequencage
Seminars in Thrombosis and Hemostasis | Year: 2011

Glanzmann thrombasthenia (GT) is the most widely studied inherited disorder of platelets; it is caused by the absence of platelet aggregation due to quantitative and/or qualitative deficiencies of the IIb3 integrin coded by the ITGA2B and ITGB3 genes located at 17q2123. Although platelet count and platelet volume (and morphology) are normal in classic GT, some reports have inferred a role for IIb3 in megakaryocytopoiesis and some novel but rare point mutations in either of the ITGA2B and ITGB3 genes have been associated with an altered platelet production and selective deficiencies in platelet function. This was brought to light by the discovery of mutations at Arg995 in IIb and Asp723 in 3 that lead to platelet anisotropy (increased size variation) and thrombocytopenia. Significantly, Arg995 and Asp723 form a salt linkage binding the cytoplasmic tails of IIb3 together keeping the integrin in a bent resting state. Mutations weakening this link (if not abolishing it) increase the activation state of IIb3 and interfere with megakaryocytopoiesis. Other mutations affecting platelet production involve extracellular but membrane proximal domains of 3. Our purpose is to review the mutations in the ITGA2B and ITGB3 genes that lead to anisotropy and to discuss mechanisms by which this can be brought about. Copyright © 2011 by Thieme Medical Publishers, Inc. Source

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