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Human T cell epitopes of Mycobacterium tuberculosis are evolutionarily hyperconserved

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      Mycobacterium tuberculosis is an obligate human pathogen capable of persisting in individual hosts for decades. To determine whether antigenic variation and immune escape contribute to the success of M. tuberculosis, we determined and analyzed 22 genome sequences representative of the global diversity of the M. tuberculosis complex (MTBC). As expected, we found that essential genes in MTBC were more evolutionarily conserved than non-essential genes. Surprisingly however, most of 491 experimentally confirmed human T cell epitopes showed little sequence variation and exhibited a lower ratio of non-synonymous to synonymous changes than essential and non-essential genes. These findings are consistent with strong purifying selection acting on these epitopes, and imply that MTBC might benefit from recognition by human T cells.

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      Most cited references 53

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          MrBayes 3 performs Bayesian phylogenetic analysis combining information from different data partitions or subsets evolving under different stochastic evolutionary models. This allows the user to analyze heterogeneous data sets consisting of different data types-e.g. morphological, nucleotide, and protein-and to explore a wide variety of structured models mixing partition-unique and shared parameters. The program employs MPI to parallelize Metropolis coupling on Macintosh or UNIX clusters.

            Author and article information

            [1 ]Medical Research Council, National Institute for Medical Research, London, NW7 1AA, UK
            [2 ]New York University School of Medicine, New York, NY 10016, USA
            [3 ]The Institute for Systems Biology and the Bill and Melinda Gates Foundation, Seattle, WA 98102, USA
            [4 ]Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
            [5 ]Research Centre Borstel, Molecular Mycobacteriology, 23845 Borstel, Germany
            [6 ]Mycobacteria Reference Laboratory (CIb-LIS), National Institute for Public Health and the Environment, 3720 BA Bilthoven, The Netherlands
            [7 ]Swiss Tropical and Public Health Institute, 4002 Basel, Switzerland
            [8 ]University of Basel, 4003 Basel, Switzerland
            Author notes
            [* ]To whom correspondence should be addressed. sebastien.gagneux@ , joel.ernst@


            I.C., J.D.E. and S.G. designed the study; P.M.S., S.N., K.K. and S.G. contributed sources of M. tuberculosis DNA and demographic information; I.C., J.C. and J.G. performed DNA sequencing and bioinformatics; I.C., P.M.S., J.D.E. and S.G. wrote the manuscript with comments from all authors.

            Nat Genet
            Nat. Genet.
            Nature genetics
            1 May 2010
            23 May 2010
            June 2010
            01 December 2010
            : 42
            : 6
            : 498-503

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            Funded by: Medical Research Council :
            Award ID: U117588500(88500) || MRC_



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