Genomic insights into tuberculosis

Prevalent since pre-history, human tuberculosis — caused by the pathogen Mycobacterium tuberculosis — remains a major source of death worldwide. Moreover, increasing drug resistance poses the threat of disease resurgence. However, the expanding application of genomic techniques is providing new avenues for combating this old foe. Whole-genome sequencing, comparative genomics and systems biology are generating new insights into the origins and ongoing evolution of M. tuberculosis, as well as the molecular basis for its pathogenicity. These have important implications for our perspective of the disease, development of new drugs and vaccines, and treatment of patients using existing therapeutics.

[1]  C. Nusbaum,et al.  ALLPATHS: de novo assembly of whole-genome shotgun microreads. , 2008, Genome research.

[2]  Stefan Niemann,et al.  High Functional Diversity in Mycobacterium tuberculosis Driven by Genetic Drift and Human Demography , 2008, PLoS biology.

[3]  W. Doolittle,et al.  Lateral gene transfer and the origins of prokaryotic groups. , 2003, Annual review of genetics.

[4]  I. Comas,et al.  A role for systems epidemiology in tuberculosis research. , 2011, Trends in microbiology.

[5]  N. Ahmed,et al.  Tuberculosis in seals caused by a novel member of the Mycobacterium tuberculosis complex: Mycobacterium pinnipedii sp. nov. , 2003, International journal of systematic and evolutionary microbiology.

[6]  M. Moroni,et al.  Spoligotyping andMycobacterium tuberculosis , 2005 .

[7]  Stephen D. Bentley,et al.  Microevolution of extensively drug-resistant tuberculosis in Russia. , 2012, Genome research.

[8]  Marcel A. Behr,et al.  Mycobacterium avium in the Postgenomic Era , 2007, Clinical Microbiology Reviews.

[9]  Amit Singh,et al.  Mycobacterium tuberculosis WhiB3 Maintains Redox Homeostasis by Regulating Virulence Lipid Anabolism to Modulate Macrophage Response , 2009, PLoS pathogens.

[10]  Timothy P. L. Smith,et al.  Reducing assembly complexity of microbial genomes with single-molecule sequencing , 2013, Genome Biology.

[11]  S. Gagneux,et al.  Does M. tuberculosis genomic diversity explain disease diversity? , 2010, Drug discovery today. Disease mechanisms.

[12]  Thomas R. Ioerger,et al.  Genome Analysis of Multi- and Extensively-Drug-Resistant Tuberculosis from KwaZulu-Natal, South Africa , 2009, PloS one.

[13]  G. Migliori,et al.  First tuberculosis cases in Italy resistant to all tested drugs. , 2007, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[14]  S. Fortune The surprising diversity of Mycobacterium tuberculosis: change you can believe in. , 2012, The Journal of infectious diseases.

[15]  Julian Parkhill,et al.  The complete genome sequence of Mycobacterium bovis , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[16]  B. Rothschild,et al.  Hyperdisease in the late Pleistocene: validation of an early 20th century hypothesis , 2006, Naturwissenschaften.

[17]  C. Roberts,et al.  Genotype of a historic strain of Mycobacterium tuberculosis , 2012, Proceedings of the National Academy of Sciences.

[18]  M. Behr Mycobacterium du jour: what's on tomorrow's menu? , 2008, Microbes and infection.

[19]  Zimmerman Mr Pulmonary and osseous tuberculosis in an Egyptian mummy. , 1979 .

[20]  Mi‐jeong Kim,et al.  Foamy macrophages and the progression of the human tuberculosis granuloma , 2009, Nature Immunology.

[21]  M. Daffé,et al.  Clinical characteristics of the smooth tubercle bacilli 'Mycobacterium canettii' infection suggest the existence of an environmental reservoir. , 2011, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[22]  Stefan Niemann,et al.  Whole-genome sequencing of rifampicin-resistant Mycobacterium tuberculosis strains identifies compensatory mutations in RNA polymerase genes , 2011 .

[23]  P. Bennett Genome plasticity: insertion sequence elements, transposons and integrons, and DNA rearrangement. , 2004, Methods in molecular biology.

[24]  C. Roberts,et al.  The Bioarchaeology of Tuberculosis: A Global View on a Reemerging Disease , 2003 .

[25]  James H. Bullard,et al.  A hybrid approach for the automated finishing of bacterial genomes , 2012, Nature Biotechnology.

[26]  R. Brosch,et al.  Ancient Origin and Gene Mosaicism of the Progenitor of Mycobacterium tuberculosis , 2005, PLoS pathogens.

[27]  Stanislas Leibler,et al.  Dynamic Persistence of Antibiotic-Stressed Mycobacteria , 2013, Science.

[28]  Y. Balabanova,et al.  Drug-resistant tuberculosis, clinical virulence, and the dominance of the Beijing strain family in Russia. , 2005, JAMA.

[29]  K. Derbyshire,et al.  IS6110, a Mycobacterium tuberculosis Complex-Specific Insertion Sequence, Is Also Present in the Genome of Mycobacterium smegmatis, Suggestive of Lateral Gene Transfer among Mycobacterial Species , 2008, Journal of bacteriology.

[30]  W. Bishai,et al.  Mechanisms of latency in Mycobacterium tuberculosis. , 1998, Trends in microbiology.

[31]  Barun Mathema,et al.  Molecular Epidemiology of Tuberculosis: Current Insights , 2006, Clinical Microbiology Reviews.

[32]  Allen D. Delaney,et al.  Genome-wide profiles of STAT1 DNA association using chromatin immunoprecipitation and massively parallel sequencing , 2007, Nature Methods.

[33]  J. Butterton,et al.  Spontaneous tandem amplification and deletion of the Shiga toxin operon in Shigella dysenteriae 1 , 1999, Molecular microbiology.

[34]  A. Nerlich,et al.  Molecular study on human tuberculosis in three geographically distinct and time delineated populations from ancient Egypt , 2003, Epidemiology and Infection.

[35]  D. Andersson,et al.  Dynamics of Antibiotic Resistant Mycobacterium tuberculosis during Long-Term Infection and Antibiotic Treatment , 2011, PloS one.

[36]  G. Schoolnik,et al.  Comparative genomics of BCG vaccines by whole-genome DNA microarray. , 1999, Science.

[37]  Clifton E. Barry,et al.  DnaE2 Polymerase Contributes to In Vivo Survival and the Emergence of Drug Resistance in Mycobacterium tuberculosis , 2003, Cell.

[38]  S. Cole,et al.  Identification of variable regions in the genomes of tubercle bacilli using bacterial artificial chromosome arrays , 1999, Molecular microbiology.

[39]  D. van Soolingen,et al.  DNA fingerprinting of Mycobacterium tuberculosis: from phage typing to whole-genome sequencing. , 2012, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[40]  P. Deschavanne,et al.  Horizontally acquired genomic islands in the tubercle bacilli. , 2008, Trends in microbiology.

[41]  T. Whittam,et al.  Restricted structural gene polymorphism in the Mycobacterium tuberculosis complex indicates evolutionarily recent global dissemination. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[42]  R. Barrangou,et al.  CRISPR Provides Acquired Resistance Against Viruses in Prokaryotes , 2007, Science.

[43]  R M Warren,et al.  IS6110-Mediated Deletion Polymorphism in the Direct Repeat Region of Clinical Isolates of Mycobacterium tuberculosis , 2003, Journal of bacteriology.

[44]  I. Smith,et al.  Cholesterol metabolism increases the metabolic pool of propionate in Mycobacterium tuberculosis. , 2009, Biochemistry.

[45]  Marcus W Feldman,et al.  Stable association between strains of Mycobacterium tuberculosis and their human host populations. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[46]  S. Gagneux Host–pathogen coevolution in human tuberculosis , 2012, Philosophical Transactions of the Royal Society B: Biological Sciences.

[47]  C. D. Long,et al.  The Competitive Cost of Antibiotic Resistance in Mycobacterium tuberculosis , 2006, Science.

[48]  Z. Udwadia,et al.  Totally drug-resistant tuberculosis (TDR-TB) in India: every dark cloud has a silver lining , 2012, Journal of Epidemiology & Community Health.

[49]  H. Swerdlow,et al.  A tale of three next generation sequencing platforms: comparison of Ion Torrent, Pacific Biosciences and Illumina MiSeq sequencers , 2012, BMC Genomics.

[50]  D. Minnikin,et al.  Detection and Molecular Characterization of 9000-Year-Old Mycobacterium tuberculosis from a Neolithic Settlement in the Eastern Mediterranean , 2008, PloS one.

[51]  D. Russell,et al.  Mycobacterium tuberculosis and the environment within the phagosome , 2007, Immunological reviews.

[52]  I. Miklós,et al.  Dynamics of Genome Rearrangement in Bacterial Populations , 2008, PLoS genetics.

[53]  Wolfgang M Prodinger,et al.  Characterization of Mycobacterium caprae Isolates from Europe by Mycobacterial Interspersed Repetitive Unit Genotyping , 2005, Journal of Clinical Microbiology.

[54]  B. Ludes,et al.  Identification of Mycobacterium DNA in an Egyptian Pott's disease of 5,400 years old. , 1998, Comptes rendus de l'Academie des sciences. Serie III, Sciences de la vie.

[55]  Parissa Farnia,et al.  Emergence of new forms of totally drug-resistant tuberculosis bacilli: super extensively drug-resistant tuberculosis or totally drug-resistant strains in iran. , 2009, Chest.

[56]  K. Holt,et al.  Out-of-Africa migration and Neolithic co-expansion of Mycobacterium tuberculosis with modern humans , 2013, Nature Genetics.

[57]  R. Chaisson,et al.  Tuberculosis drug resistance: a global threat. , 2003, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[58]  W. Stead,et al.  The history of tuberculosis as a global epidemic. , 1993, The Medical clinics of North America.

[59]  J. Mittler,et al.  A replication clock for Mycobacterium tuberculosis , 2009, Nature Medicine.

[60]  Yves Van de Peer,et al.  The Mycobacterium tuberculosis regulatory network and hypoxia , 2013, Nature.

[61]  Aaron L. Halpern,et al.  Consensus generation and variant detection by Celera Assembler , 2008, Bioinform..

[62]  J. McInerney,et al.  Fatty acid biosynthesis in Mycobacterium tuberculosis: Lateral gene transfer, adaptive evolution, and gene duplication , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[63]  Z. F. Zainuddin,et al.  Characterization of a Mycobacterium tuberculosis insertion sequence belonging to the IS3 family , 1990, Molecular microbiology.

[64]  Markus R. Wenk,et al.  Triacylglycerol Utilization Is Required for Regrowth of In Vitro Hypoxic Nonreplicating Mycobacterium bovis Bacillus Calmette-Guerin , 2009, Journal of bacteriology.

[65]  M. Zimmerman Pulmonary and osseous tuberculosis in an Egyptian mummy. , 1979, Bulletin of the New York Academy of Medicine.

[66]  S. Niemann,et al.  The Beijing genotype is a major cause of drug-resistant tuberculosis in Kazakhstan. , 2005, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[67]  Beatriz Galán,et al.  Characterization of the KstR-dependent promoter of the gene for the first step of the cholesterol degradative pathway in Mycobacterium smegmatis. , 2011, Microbiology.

[68]  M. Reed,et al.  Massive Gene Duplication Event among Clinical Isolates of the Mycobacterium tuberculosis W/Beijing Family , 2010, Journal of bacteriology.

[69]  Gilles Vergnaud,et al.  Molecular characteristics of "Mycobacterium canettii" the smooth Mycobacterium tuberculosis bacilli. , 2010, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[70]  Daniel R Zerbino,et al.  Using the Velvet de novo Assembler for Short‐Read Sequencing Technologies , 2010, Current protocols in bioinformatics.

[71]  A. Nerlich,et al.  Molecular history of tuberculosis from ancient mummies and skeletons , 2007 .

[72]  M. Chase,et al.  Use of whole genome sequencing to estimate the mutation rate of Mycobacterium tuberculosis during latent infection , 2011, Nature Genetics.

[73]  D. Russell The evolutionary pressures that have molded Mycobacterium tuberculosis into an infectious adjuvant. , 2013, Current opinion in microbiology.

[74]  D. Cousins,et al.  Tuberculosis in imported hyrax (Procavia capensis) caused by an unusual variant belonging to the Mycobacterium tuberculosis complex. , 1994, Veterinary microbiology.

[75]  S. Gillespie,et al.  Physiological Cost of Rifampin Resistance Induced In Vitro in Mycobacterium tuberculosis , 1999, Antimicrobial Agents and Chemotherapy.

[76]  U. Alon Network motifs: theory and experimental approaches , 2007, Nature Reviews Genetics.

[77]  P. V. van Helden,et al.  Novel Mycobacterium tuberculosis Complex Pathogen, M. mungi , 2010, Emerging infectious diseases.

[78]  Jun Yu,et al.  BIGrat: a repeat resolver for pyrosequencing-based re-sequencing with Newbler , 2012, BMC Research Notes.

[79]  A. Nerlich,et al.  Molecular analysis of skeletal tuberculosis in an ancient Egyptian population. , 2001, Journal of medical microbiology.

[80]  P. Bourgine,et al.  Topological and causal structure of the yeast transcriptional regulatory network , 2002, Nature Genetics.

[81]  M. Elowitz,et al.  Functional Roles of Pulsing in Genetic Circuits , 2013, Science.

[82]  V. Formicola,et al.  Evidence of spinal tuberculosis at the beginning of the fourth millennium BC from Arene Candide cave (Liguria, Italy). , 1987, American journal of physical anthropology.

[83]  M. Drancourt,et al.  Imported extensively drug-resistant Mycobacterium tuberculosis Beijing genotype, Marseilles, France, 2011. , 2011, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[84]  E. Böttger,et al.  Fitness Cost of Chromosomal Drug Resistance-Conferring Mutations , 2002, Antimicrobial Agents and Chemotherapy.

[85]  S. Cole,et al.  Effect of katG Mutations on the Virulence of Mycobacterium tuberculosis and the Implication for Transmission in Humans , 2002, Infection and Immunity.

[86]  E. Muñoz-Elías,et al.  Mycobacterium tuberculosis isocitrate lyases 1 and 2 are jointly required for in vivo growth and virulence , 2005, Nature Medicine.

[87]  H. Ochman,et al.  Lateral gene transfer and the nature of bacterial innovation , 2000, Nature.

[88]  A. Aufderheide,et al.  Identification of Mycobacterium tuberculosis DNA in a pre-Columbian Peruvian mummy. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[89]  Markus Sköld,et al.  Tuberculosis and HIV Co-Infection , 2012, PLoS pathogens.

[90]  M. Behr,et al.  Mycobacterium avium subsp. paratuberculosis and M. avium subsp. avium Are Independently Evolved Pathogenic Clones of a Much Broader Group of M. avium Organisms , 2008, Journal of bacteriology.

[91]  Falk Hildebrand,et al.  Origin, Spread and Demography of the Mycobacterium tuberculosis Complex , 2008, PLoS pathogens.

[92]  P. V. van Helden,et al.  IS6110-Mediated Deletion Polymorphism in Isogenic Strains of Mycobacterium tuberculosis , 2004, Journal of Clinical Microbiology.

[93]  Julian Parkhill,et al.  Insights from the complete genome sequence of Mycobacterium marinum on the evolution of Mycobacterium tuberculosis. , 2008, Genome research.

[94]  P. V. van Helden,et al.  Drug-resistant tuberculosis epidemic in the Western Cape driven by a virulent Beijing genotype strain. , 2010, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[95]  J. Collins,et al.  Role of reactive oxygen species in antibiotic action and resistance. , 2009, Current opinion in microbiology.

[96]  J. Galagan,et al.  Human T cell epitopes of Mycobacterium tuberculosis are evolutionarily hyperconserved , 2010, Nature Genetics.

[97]  Midori Kato-Maeda,et al.  Functional and evolutionary genomics of Mycobacterium tuberculosis: insights from genomic deletions in 100 strains. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[98]  J. Emile,et al.  Foamy Macrophages from Tuberculous Patients' Granulomas Constitute a Nutrient-Rich Reservoir for M. tuberculosis Persistence , 2008, PLoS pathogens.

[99]  A. Regev,et al.  Impulse Control: Temporal Dynamics in Gene Transcription , 2011, Cell.

[100]  C. Buchrieser,et al.  A new evolutionary scenario for the Mycobacterium tuberculosis complex , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[101]  T. M. Daniel,et al.  Old Testament biblical references to tuberculosis. , 1999, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[102]  E. Willery,et al.  Genome analysis of smooth tubercle bacilli provides insights into ancestry and pathoadaptation of the etiologic agent of tuberculosis , 2013, Nature Genetics.

[103]  M. Moroni,et al.  Spoligotyping and Mycobacterium tuberculosis , 2005, Emerging infectious diseases.

[104]  Sebastien Gagneux,et al.  Global phylogeography of Mycobacterium tuberculosis and implications for tuberculosis product development. , 2007, The Lancet. Infectious diseases.

[105]  U. Schaible,et al.  The Granuloma in Tuberculosis: Dynamics of a Host–Pathogen Collusion , 2012, Front. Immun..

[106]  J. Musser,et al.  Negligible genetic diversity of mycobacterium tuberculosis host immune system protein targets: evidence of limited selective pressure. , 2000, Genetics.

[107]  B. Rothschild,et al.  Did ice-age bovids spread tuberculosis? , 2006, Naturwissenschaften.

[108]  J. Sacchettini,et al.  The non-clonality of drug resistance in Beijing-genotype isolates of Mycobacterium tuberculosis from the Western Cape of South Africa , 2010, BMC Genomics.

[109]  M. Behr,et al.  The rise and fall of the Mycobacterium tuberculosis genome. , 2011, Trends in microbiology.

[110]  David G. Russell,et al.  Mycobacterium tuberculosis: here today, and here tomorrow , 2001, Nature Reviews Molecular Cell Biology.

[111]  B. Robertson,et al.  Comparison of Mycobacterium Tuberculosis Genomes Reveals Frequent Deletions in a 20 kb Variable Region in Clinical Isolates , 2000, Yeast.

[112]  Nalin Rastogi,et al.  Characterization of Mycobacterium tuberculosis Complex DNAs from Egyptian Mummies by Spoligotyping , 2003, Journal of Clinical Microbiology.

[113]  B. Wang,et al.  Outbreak of tuberculosis in a 2000-year-old Chinese population. , 2003, Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases.

[114]  M. DePristo,et al.  Sublethal antibiotic treatment leads to multidrug resistance via radical-induced mutagenesis. , 2010, Molecular cell.

[115]  Floyd E. Romesberg,et al.  Induction and Inhibition of Ciprofloxacin Resistance-Conferring Mutations in Hypermutator Bacteria , 2006, Antimicrobial Agents and Chemotherapy.

[116]  P. V. van Helden,et al.  Putative Compensatory Mutations in the rpoC Gene of Rifampin-Resistant Mycobacterium tuberculosis Are Associated with Ongoing Transmission , 2012, Antimicrobial Agents and Chemotherapy.

[117]  E. Rocha,et al.  After the bottleneck: Genome-wide diversification of the Mycobacterium tuberculosis complex by mutation, recombination, and natural selection. , 2012, Genome research.

[118]  Alicia Aranaz,et al.  Genomic deletions suggest a phylogeny for the Mycobacterium tuberculosis complex. , 2002, The Journal of infectious diseases.

[119]  David G. Russell,et al.  Mycobacterium and the coat of many lipids , 2002, The Journal of cell biology.

[120]  Nalin Rastogi,et al.  Proposal for Standardization of Optimized Mycobacterial Interspersed Repetitive Unit-Variable-Number Tandem Repeat Typing of Mycobacterium tuberculosis , 2006, Journal of Clinical Microbiology.

[121]  Sharon L. Kendall,et al.  Cholesterol utilization in mycobacteria is controlled by two TetR-type transcriptional regulators: kstR and kstR2 , 2010, Microbiology.

[122]  L. Marraffini,et al.  CRISPR Interference Limits Horizontal Gene Transfer in Staphylococci by Targeting DNA , 2008, Science.

[123]  D. Russell Mycobacterium tuberculosis and the intimate discourse of a chronic infection , 2011, Immunological reviews.

[124]  C. Locht,et al.  Linkage disequilibrium between minisatellite loci supports clonal evolution of Mycobacterium tuberculosis in a high tuberculosis incidence area , 2003, Molecular microbiology.

[125]  Stefan Niemann,et al.  Variable host-pathogen compatibility in Mycobacterium tuberculosis. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[126]  S. Gordon,et al.  Mycobacterial Lineages Causing Pulmonary and Extrapulmonary Tuberculosis, Ethiopia , 2013, Emerging infectious diseases.

[127]  D. van Soolingen,et al.  The re-emergence of tuberculosis: what have we learnt from molecular epidemiology? , 2013, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[128]  Marisa Klopper,et al.  Emergence and Spread of Extensively and Totally Drug-Resistant Tuberculosis, South Africa , 2013, Emerging infectious diseases.

[129]  Guido N. J. Tytgat,et al.  Genomic Analysis Reveals Variation between Mycobacterium tuberculosis H37Rv and the Attenuated M. tuberculosis H37Ra Strain , 1999 .

[130]  H. Meller,et al.  Rib lesions in skeletons from early neolithic sites in Central Germany: on the trail of tuberculosis at the onset of agriculture. , 2012, American journal of physical anthropology.

[131]  Q. Gao,et al.  Phylogeny of Mycobacterium tuberculosis Beijing Strains Constructed from Polymorphisms in Genes Involved in DNA Replication, Recombination and Repair , 2011, PloS one.

[132]  P. V. van Helden,et al.  Mutation rate and the emergence of drug resistance in Mycobacterium tuberculosis. , 2014, The Journal of antimicrobial chemotherapy.

[133]  P. Deschavanne,et al.  Contribution of horizontally acquired genomic islands to the evolution of the tubercle bacilli. , 2007, Molecular biology and evolution.

[134]  C. Boesch,et al.  Novel Mycobacterium tuberculosis Complex Isolate from a Wild Chimpanzee , 2013, Emerging infectious diseases.

[135]  R. Sharan,et al.  Protein networks in disease. , 2008, Genome research.

[136]  G. Besra,et al.  A novel pathogenic taxon of the Mycobacterium tuberculosis complex, Canetti: characterization of an exceptional isolate from Africa. , 1997, International journal of systematic bacteriology.

[137]  Omar E. Cornejo,et al.  The Role of Selection in Shaping Diversity of Natural M. tuberculosis Populations , 2013, PLoS pathogens.

[138]  Yang Liu,et al.  Transcriptional Adaptation of Mycobacterium tuberculosis within Macrophages , 2003, The Journal of experimental medicine.

[139]  Irina Kolesnikova,et al.  A Thiolase of Mycobacterium tuberculosis Is Required for Virulence and Production of Androstenedione and Androstadienedione from Cholesterol , 2009, Infection and Immunity.

[140]  Weidong Tian,et al.  Dynamic population changes in Mycobacterium tuberculosis during acquisition and fixation of drug resistance in patients. , 2012, The Journal of infectious diseases.

[141]  K. Dooley,et al.  Tuberculosis and diabetes mellitus: convergence of two epidemics. , 2009, The Lancet. Infectious diseases.

[142]  T. Mikkelsen,et al.  Genome-wide maps of chromatin state in pluripotent and lineage-committed cells , 2007, Nature.

[143]  A. Gnirke,et al.  ALLPATHS 2: small genomes assembled accurately and with high continuity from short paired reads , 2009, Genome Biology.

[144]  Dr. Susumu Ohno Evolution by Gene Duplication , 1970, Springer Berlin Heidelberg.

[145]  H. Maamar,et al.  Mycobacterium tuberculosis Uses Host Triacylglycerol to Accumulate Lipid Droplets and Acquires a Dormancy-Like Phenotype in Lipid-Loaded Macrophages , 2011, PLoS pathogens.

[146]  A. Nerlich,et al.  Paleopathology of Human Tuberculosis and the Potential Role of Climate , 2009, Interdisciplinary perspectives on infectious diseases.

[147]  B. Arriaza,et al.  Pre-Columbian tuberculosis in northern Chile: molecular and skeletal evidence. , 1995, American journal of physical anthropology.

[148]  A. Mortazavi,et al.  Genome-Wide Mapping of in Vivo Protein-DNA Interactions , 2007, Science.

[149]  J. Collins,et al.  Microbial persistence and the road to drug resistance. , 2013, Cell host & microbe.

[150]  Monographies,et al.  MRSA: A Global Threat , 2012 .

[151]  Steven J. M. Jones,et al.  Whole-genome sequencing and social-network analysis of a tuberculosis outbreak. , 2011, The New England journal of medicine.

[152]  M. Moroni,et al.  Comparison between spoligotyping and IS6110 restriction fragment length polymorphisms in molecular genotyping analysis of Mycobacterium tuberculosis strains. , 2005, Molecular and cellular probes.

[153]  S. Gillespie,et al.  Comparison of fitness of two isolates of Mycobacterium tuberculosis, one of which had developed multi-drug resistance during the course of treatment. , 2000, The Journal of infection.

[154]  Serge Mostowy,et al.  The origin and evolution of Mycobacterium tuberculosis. , 2005, Clinics in chest medicine.

[155]  B. Birren,et al.  Independent Large Scale Duplications in Multiple M. tuberculosis Lineages Overlapping the Same Genomic Region , 2012, PloS one.

[156]  T. Whittam,et al.  Is Mycobacterium tuberculosis 15,000 years old? , 1994, The Journal of infectious diseases.

[157]  V. Møller-Christensen,et al.  A case of spondylitis tuberculosa in the Danish Neolithic Age. , 1972, Danish medical bulletin.

[158]  E. Böttger,et al.  Fitness of antibiotic-resistant microorganisms and compensatory mutations , 1998, Nature Medicine.

[159]  P. Farnham Insights from genomic profiling of transcription factors , 2009, Nature Reviews Genetics.

[160]  David G. Russell,et al.  Who puts the tubercle in tuberculosis? , 2007, Nature Reviews Microbiology.

[161]  Daniel J. Wilson,et al.  Whole-genome sequencing to delineate Mycobacterium tuberculosis outbreaks: a retrospective observational study , 2013, The Lancet. Infectious diseases.

[162]  Amit Singh,et al.  Mycobacterium tuberculosis WhiB3 responds to O2 and nitric oxide via its [4Fe-4S] cluster and is essential for nutrient starvation survival , 2007, Proceedings of the National Academy of Sciences.

[163]  E. Muñoz-Elías,et al.  Replication Dynamics of Mycobacterium tuberculosis in Chronically Infected Mice , 2005, Infection and Immunity.

[164]  Ben Shields The Bioarchaeology of Tuberculosis: A Global View on a Reemerging Disease , 2005 .

[165]  Linus Sandegren,et al.  Bacterial gene amplification: implications for the evolution of antibiotic resistance , 2009, Nature Reviews Microbiology.

[166]  S. Gharbia,et al.  Multispacer Sequence Typing for Mycobacterium tuberculosis Genotyping , 2008, PloS one.

[167]  S. Borrell,et al.  The heterogeneous evolution of multidrug-resistant Mycobacterium tuberculosis. , 2013, Trends in genetics : TIG.

[168]  M. Behr,et al.  Insertion and Deletion Events That Define the Pathogen Mycobacterium avium subsp. paratuberculosis , 2008, Journal of bacteriology.

[169]  Julian Parkhill,et al.  Whole-genome sequencing to establish relapse or re-infection with Mycobacterium tuberculosis: a retrospective observational study , 2013, The Lancet. Respiratory medicine.

[170]  C. Markert,et al.  Evolution of the Gene , 1948, Nature.

[171]  B. Barrell,et al.  Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence , 1998, Nature.

[172]  M. Bennett,et al.  Microfluidic devices for measuring gene network dynamics in single cells , 2009, Nature Reviews Genetics.

[173]  S. Kaufmann,et al.  How can immunology contribute to the control of tuberculosis? , 2001, Nature Reviews Immunology.

[174]  S. Gagneux Genetic diversity in Mycobacterium tuberculosis. , 2013, Current topics in microbiology and immunology.

[175]  Leen Rigouts,et al.  Mycobacterium tuberculosis complex genetic diversity: mining the fourth international spoligotyping database (SpolDB4) for classification, population genetics and epidemiology , 2006, BMC Microbiology.

[176]  Stefan Niemann,et al.  Mycobacterium tuberculosis wears what it eats. , 2010, Cell host & microbe.

[177]  A. Stone,et al.  Tuberculosis on the north coast of Peru: skeletal and molecular paleopathology of late pre-Hispanic and postcontact mycobacterial disease , 2010 .

[178]  C. Sizer Diseases in Antiquity: A Survey of the Diseases, Injuries and Surgery of Early Populations , 1969, Medical History.

[179]  Uri Alon,et al.  An Introduction to Systems Biology , 2006 .

[180]  Galit Lev-Maor,et al.  Tuberculosis: from prehistory to Robert Koch, as revealed by ancient DNA. , 2004, The Lancet. Infectious diseases.

[181]  M. Behr,et al.  Inter- and Intra-subtype genotypic differences that differentiate Mycobacterium avium subspecies paratuberculosis strains , 2012, BMC Microbiology.

[182]  P. V. Prasad General medicine in Atharvaveda with special reference to Yaksma (consumption/tuberculosis). , 2002, Bulletin of the Indian Institute of History of Medicine.

[183]  Marc Lipsitch,et al.  Mycobacterium tuberculosis mutation rate estimates from different lineages predict substantial differences in the emergence of drug resistant tuberculosis , 2013, Nature Genetics.

[184]  Ben Sidders,et al.  A highly conserved transcriptional repressor controls a large regulon involved in lipid degradation in Mycobacterium smegmatis and Mycobacterium tuberculosis , 2007, Molecular microbiology.

[185]  Anna Lyubetskaya,et al.  ChIP-Seq and the complexity of bacterial transcriptional regulation. , 2013, Current topics in microbiology and immunology.