Key Points
-
The M. tuberculosis complex (with the exception of M. canettii) shows little evidence for the transfer and recombination of chromosomal genes. We discuss the remarkable consequences of this strict clonality, and show how selective sweeps and population bottlenecks can profoundly reduce the diversity of the population.
-
The clonality of this group of organisms has shaped the phylogeny of the M. tuberculosis complex and we suggest that they might best be described as a group of host-adapted ecotypes rather than species. Our analysis highlights the close sequence similarity of these ecotypes and the facility these organisms have for invading and establishing themselves in new mammalian hosts.
-
The history and molecular epidemiology of bovine tuberculosis in the British Isles is then reviewed. A test and slaughter programme was initially highly successful at reducing the incidence of disease but, since the 1980s (and in contrast to the rest of Europe), has failed to control an exponential increase in incidents.
-
The molecular epidemiology of bovine tuberculosis reveals that a single clonal complex of strains has come to dominate throughout the British Isles and is responsible for over 85% of the bovine tuberculosis in Great Britain. We suggest that the limited diversity of M. bovis in the British Isles is a result of a population bottleneck induced by more than 100 years of bovine tuberculosis control programmes, in particular the extensive test and slaughter regime. The recent dominance and exponential increase of a single clonal complex can best be explained by selection, and two possible selective advantages of the dominant clonal complex in the British Isles are discussed.
-
Finally, we show how an understanding of the population structure and molecular epidemiology of this disease has contributed to our appreciation of the role of cattle movement and badgers in the spread and maintenance of the disease, and we describe the practical application to the development of advanced techniques of diagnosis and vaccination.
Abstract
Mycobacterium bovis is the cause of tuberculosis in cattle and is a member of the Mycobacterium tuberculosis complex. In contrast to many other pathogenic bacterial species, there is little evidence for the transfer and recombination of genes between cells. The clonality of this group of organisms indicates that the population structure is dominated by reductions in diversity, caused either by population bottlenecks or selective sweeps as entire chromosomes become fixed in the population. We describe how these forces have shaped not only the phylogeny of this group but also, at a very local level, the population structure of Mycobacterium bovis in the British Isles. We also discuss the practical implications of applying this knowledge to understanding the spread of infection and the development of improved vaccines and diagnostic tests.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Corbett, E. L. et al. The growing burden of tuberculosis: global trends and interactions with the HIV epidemic. Arch. Intern. Med. 163, 1009–1021 (2003).
Raviglione, M. C., Snider, D. E. Jr. & Kochi, A. Global epidemiology of tuberculosis. Morbidity and mortality of a worldwide epidemic. JAMA 273, 220–226 (1995).
Dye, C., Scheele, S., Dolin, P., Pathania, V. & Raviglione, M. C. Consensus statement.Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country. WHO Global Surveillance and Monitoring Project. JAMA 282, 677–686 (1999).
WHO. Bulletin of the World Health Organisation. Int. J. Public Health 80, 426–523 (2002).
Smith, N. H. et al. Ecotypes of the Mycobacterium tuberculosis complex. J. Theor. Biol. 239, 220–225 (2006). Identifies a series of clades in the animal-adapted lineage of the M. tuberculosis complex and suggests that these bacteria are best described as a series of host-adapted ecotypes rather than species.
Brosch, R. et al. A new evolutionary scenario for the Mycobacterium tuberculosis complex. Proc. Natl Acad. Sci. USA 99, 3684–3689 (2002). A seminal manuscript that identifies the backbone phylogeny of the M. tuberculosis complex based on a series of informative deletions.
Sreevatsan, S. et al. Restricted structural gene polymorphism in the Mycobacterium tuberculosis complex indicates evolutionarily recent global dissemination. Proc. Natl Acad. Sci. USA 94, 9869–9874 (1997).
Huard, R. C. et al. Novel genetic polymorphisms that further delineate the phylogeny of the Mycobacterium tuberculosis complex. J. Bacteriol. 188, 4271–4287 (2006).
Garnier, T. et al. The complete genome sequence of Mycobacterium bovis. Proc. Natl Acad. Sci. USA 100, 7877–7882 (2003).
Perna, N. T. et al. Genome sequence of enterohaemorrhagic Escherichia coli O157:H7. Nature 409, 529–533 (2001).
Li, W. H. & Sadler, L. A. Low nucleotide diversity in man. Genetics 129, 513–523 (1991).
Cargill, M. et al. Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nature Genet. 22, 231–238 (1999).
Gutierrez, M. C. et al. Ancient origin and gene mosaicism of the progenitor of Mycobacterium tuberculosis. PLoS Pathogens 1, e5 (2005).
Maynard Smith, J., Smith, N. H., O'Rourke, M. & Spratt, B. G. How clonal are bacteria? Proc. Natl Acad. Sci. USA 90, 4384–4388 (1993). An important insight into bacterial population genetics and structure. This manuscript shows how bacterial populations can range from the panmictic to the purely clonal.
Supply, P. et al. Linkage disequilibrium between minisatellite loci supports clonal evolution of Mycobacterium tuberculosis in a high tuberculosis incidence area. Mol. Microbiol. 47, 529–538 (2003).
Cole, S. T. et al. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393, 537–544 (1998).
Baker, L., Brown, T., Maiden, M. C. & Drobniewski, F. Silent nucleotide polymorphisms and a phylogeny for Mycobacterium tuberculosis. Emerg. Infect. Dis. 10, 1568–1577 (2004).
Filliol, I. et al. Global phylogeny of Mycobacterium tuberculosis based on single nucleotide polymorphism (SNP) analysis: insights into tuberculosis evolution, phylogenetic accuracy of other DNA fingerprinting systems, and recommendations for a minimal standard SNP set. J. Bacteriol. 188, 759–772 (2006).
Brosch, R., Pym, A. S., Gordon, S. V. & Cole, S. T. The evolution of mycobacterial pathogenicity: clues from comparative genomics. Trends Microbiol. 9, 452–458 (2001).
Gutacker, M. M. et al. Genome-wide analysis of synonymous single nucleotide polymorphisms in Mycobacterium tuberculosis complex organisms: resolution of genetic relationships among closely related microbial strains. Genetics 162, 1533–1543 (2002).
Gutacker, M. M. et al. Single-nucleotide polymorphism-based population genetic analysis of Mycobacterium tuberculosis strains from 4 geographic sites. J. Infect. Dis. 193, 121–128 (2006).
Hirsh, A. E., Tsolaki, A. G., DeRiemer, K., Feldman, M. W. & Small, P. M. Stable association between strains of Mycobacterium tuberculosis and their human host populations. Proc. Natl Acad. Sci. USA 101, 4871–4876 (2004).
Hughes, A. L., Friedman, R. & Murray, M. Genomewide pattern of synonymous nucleotide substitution in two complete genomes of Mycobacterium tuberculosis. Emerg. Infect. Dis. 8, 1342–1346 (2002).
Maynard Smith, J. & Smith, N. H. Detecting recombination from gene trees. Mol. Biol. Evol. 15, 590–599 (1998).
Smith, N. H., Beltran, P. & Selander, R. K. Recombination of Salmonella phase 1 flagellin genes generates new serovars. J. Bacteriol. 172, 2209–2216 (1990).
Barcus, V. A. & Murray, N. E. in Population Genetics of Bacteria (52nd SGM Symposium) (eds Baumbergs, S. et al.) 31–58 (Cambridge Univ. Press, Cambridge, 1995).
van Soolingen, D. et al. A novel pathogenic taxon of the Mycobacterium tuberculosis complex, Canetti: characterization of an exceptional isolate from Africa. Int. J. Syst. Bacteriol. 47, 1236–1245 (1997).
Mostowy, S., Cousins, D., Brinkman, J., Aranaz, A. & Behr, M. A. Genomic deletions suggest a phylogeny for the Mycobacterium tuberculosis complex. J. Infect. Dis. 186, 74–80 (2002).
Mahairas, G. G., Sabo, P. J., Hickey, M. J., Singh, D. C. & Stover, C. K. Molecular analysis of genetic differences between Mycobacterium bovis BCG and virulent M. bovis. J. Bacteriol. 178, 1274–1282 (1996).
Gordon, S. V. et al. Genomics of Mycobacterium bovis. Tuberculosis (Edinb) 81, 157–163 (2001).
Behr, M. A. et al. Comparative genomics of BCG vaccines by whole-genome DNA microarray. Science 284, 1520–1523 (1999).
de Jong, B. C. et al. Mycobacterium africanum: a new opportunistic pathogen in HIV infection? Aids 19, 1714–1715 (2005).
Niobe-Eyangoh, S. N. et al. Genetic biodiversity of Mycobacterium tuberculosis complex strains from patients with pulmonary tuberculosis in Cameroon. J. Clin. Microbiol. 41, 2547–2553 (2003).
Mostowy, S. et al. Genomic analysis distinguishes Mycobacterium africanum. J. Clin. Microbiol. 42, 3594–3599 (2004).
Cohan, F. M. What are bacterial species? Annu. Rev. Microbiol. 56, 457–487 (2002). Explains the ecotype concept for identifying bacterial populations with similar properties to eukaryotic species.
Mostowy, S. et al. Revisiting the evolution of Mycobacterium bovis. J. Bacteriol. 187, 6386–6395 (2005).
Gagneux, S. et al. Variable host–pathogen compatibility in Mycobacterium tuberculosis. Proc. Natl Acad. Sci. USA 103, 2869–2873 (2006).
Rad, M. E. et al. Mutations in putative mutator genes of Mycobacterium tuberculosis strains of the W-Beijing family. Emerg. Infect. Dis. 9, 838–845 (2003).
Lopez, B. et al. A marked difference in pathogenesis and immune response induced by different Mycobacterium tuberculosis genotypes. Clin. Exp. Immunol. 133, 30–37 (2003).
Glynn, J. R., Whiteley, J., Bifani, P. J., Kremer, K. & van Soolingen, D. Worldwide occurrence of Beijing/W strains of Mycobacterium tuberculosis: a systematic review. Emerg. Infect. Dis. 8, 843–849 (2002).
Zhang, M. et al. Enhanced capacity of a widespread strain of Mycobacterium tuberculosis to grow in human macrophages. J. Infect. Dis. 179, 1213–1217 (1999).
Reed, M. B. et al. A glycolipid of hypervirulent tuberculosis strains that inhibits the innate immune response. Nature 431, 84–87 (2004).
Atwood, K. C. & Ryan, F. J. Periodic selection in Escherichia coli. Proc. Natl Acad. Sci. USA 37, 146–155 (1951).
Maynard Smith, J. & Haigh, J. The hitch-hiking effect of a favourable gene. Genet. Res. 23, 23–35 (1974).
Caballero, A. Developments in the prediction of effective population size. Heredity 73, 657–679 (1994).
Mayr, E. Animal Species and Evolution (Harvard Univ. Press, Cambridge, Massachusetts, 1963).
Kimura, M. The Neutral Theory of Molecular Evolution (Cambridge Univ. Press, Cambridge, 1983).
Rocha, E. P. et al. Comparisons of dN/dS are time dependent for closely related bacterial genomes. J. Theor. Biol. 239, 226–235 (2006).
Tweddle, N. E. & Livingstone, P. Bovine tuberculosis control and eradication programs in Australia and New Zealand. Vet. Microbiol. 40, 23–39 (1994).
de Kantor, I. N. & Ritacco, V. An update on bovine tuberculosis programmes in Latin American and Caribbean countries. Vet. Microbiol. 112, 111–118 (2006).
Ryan, T. J. et al. Advances in understanding disease epidemiology and implications for control and eradication of tuberculosis in livestock: the experience from New Zealand. Vet. Microbiol. 112, 211–219 (2006).
O'Brien, D. J., Schmitt, S. M., Fitzgerald, S. D., Berry, D. E. & Hickling, G. J. Managing the wildlife reservoir of Mycobacterium bovis: the Michigan, USA, experience. Vet. Microbiol. 112, 313–323 (2006).
Nishi, J. S., Shury, T. & Elkin, B. T. Wildlife reservoirs for bovine tuberculosis (Mycobacterium bovis) in Canada: strategies for management and research. Vet. Microbiol. 112, 325–338 (2006).
Michel, A. L. et al. Wildlife tuberculosis in South African conservation areas: implications and challenges. Vet. Microbiol. 112, 91–100 (2006).
Hewinson, R. G., Vordermeier, H. M., Smith, N. H. & Gordon, S. V. Recent advances in our knowledge of Mycobacterium bovis: a feeling for the organism. Vet. Microbiol. 112, 127–139 (2006).
Reviriego Gordejo, F. J. & Vermeersch, J. P. Towards eradication of bovine tuberculosis in the European Union. Vet. Microbiol. 112, 101–109 (2006).
Pavlik, I. The experience of new European Union Member States concerning the control of bovine tuberculosis. Vet. Microbiol. 112, 221–230 (2006).
DEFRA. Animal Health 2005. The report of the Chief Veterinary Officer DEFRA Animal Health [online], http://www.defra.gov.uk/animalh/cvo/report/2005/index.htm (2006).
Abernethy, D. A. et al. The Northern Ireland programme for the control and eradication of Mycobacterium bovis. Vet. Microbiol. 112, 231–237 (2006).
Moore, S. I. & Good, M. The tuberculosis eradication programme in Ireland: a review of scientific and policy advances since 1988. Vet. Microbiol. 112, 239–251 (2006).
Good, M. Bovine tuberculosis eradication in Ireland. Irish Vet. J. 59, 154–160 (2006).
Donnelly, C. A. et al. Positive and negative effects of widespread badger culling on tuberculosis in cattle. Nature 439, 843–846 (2006).
Griffin, J. M. et al. The impact of badger removal on the control of tuberculosis in cattle herds in Ireland. Prev. Vet. Med. 67, 237–266 (2005).
Mairtin, D. O., Williams, D. H., Griffin, J. M., Dolan, L. A. & Eves, J. A. The effect of a badger removal programme on the incidence of tuberculosis in an Irish cattle population. Prev. Vet. Med. 34, 47–56 (1998).
de la Rua-Domenech, R. Human Mycobacterium bovis infection in the United Kingdom: incidence, risks, control measures and review of the zoonotic aspects of bovine tuberculosis. Tuberculosis (Edinb) 86, 77–109 (2006). An in-depth review of the history and impact of bovine tuberculosis in the United Kingdom.
Gibson, A. L. et al. Molecular epidemiology of disease due to Mycobacterium bovis in humans in the United Kingdom. J. Clin. Microbiol. 42, 431–434 (2004).
Maiden, M. C. et al. Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms. Proc. Natl Acad. Sci. USA 95, 3140–3145 (1998).
Fang, Z., Morrison, N., Watt, B., Doig, C. & Forbes, K. J. IS6110 transposition and evolutionary scenario of the direct repeat locus in a group of closely related Mycobacterium tuberculosis strains. J. Bacteriol. 180, 2102–2109 (1998).
Warren, R. M. et al. Microevolution of the direct repeat region of Mycobacterium tuberculosis: implications for interpretation of spoligotyping data. J. Clin. Microbiol. 40, 4457–4465 (2002).
Kremer, K. et al. Use of variable-number tandem-repeat typing to differentiate Mycobacterium tuberculosis Beijing family isolates from Hong Kong and comparison with IS6110 restriction fragment length polymorphism typing and spoligotyping. J. Clin. Microbiol. 43, 314–320 (2005).
Gibson, A., Brown, T., Baker, L. & Drobniewski, F. Can 15-locus mycobacterial interspersed repetitive unit-variable-number tandem repeat analysis provide insight into the evolution of Mycobacterium tuberculosis? Appl. Environ. Microbiol. 71, 8207–8213 (2005).
Frothingham, R. & Meeker-O'Connell, W. A. Genetic diversity in the Mycobacterium tuberculosis complex based on variable numbers of tandem DNA repeats. Microbiology 144, 1189–1196 (1998).
Smith, N. H. et al. The population structure of Mycobacterium bovis in Great Britain: clonal expansion. Proc. Natl Acad. Sci. USA 100, 15271–15275 (2003).
Haddad, N. et al. Spoligotype diversity of Mycobacterium bovis strains isolated in France from 1979 to 2000. J. Clin. Microbiol. 39, 3623–3632 (2001).
Skuce, R. A. et al. Discrimination of isolates of Mycobacterium bovis in Northern Ireland on the basis of variable numbers of tandem repeats (VNTRs). Vet. Rec. 157, 501–504 (2005).
Crow, J. F. & Kimura, M. An Introduction to Population Genetics Theory (Harper & Row, New York, 1970).
Commission Decision 2001/26/EC of 27 December 2000, amending for the fourth time Decision 1999/467/EC establishing the officially tuberculosis-free status of bovine herds of certain Member States or regions of Member States. 11 January 2001. Official Journal of the European Union L006 13–19 (2000).
Wahlund, S. Zusammensetzung von Population und Korrelationserscheinung vom Standpunkt der Vererbungslehre aus betrachtet. Hereditas 11, 65–106 (1928) (in German).
Haddad, N., Masselot, M. & Durand, B. Molecular differentiation of Mycobacterium bovis isolates. Review of main techniques and applications. Res. Vet. Sci. 76, 1–18 (2004).
Cataldi, A. A. et al. The genotype of the principal Mycobacterium bovis in Argentina is also that of the British Isles: did bovine tuberculosis come from Great Britain? Rev. Argent. Microbiol. 34, 1–6 (2002).
Njanpop-Lafourcade, B. M. et al. Molecular typing of Mycobacterium bovis isolates from Cameroon. J. Clin. Microbiol. 39, 222–227 (2001).
Koonin, E. V., Makarova, K. S., Grishin, N. V., Wolf, Y. I. in Prokaryotic Diversity (66th SGM symposium) (eds Logan, N. A., Lappin-Scott, H. M. & Oyston, P. C. F) 39–64, (Cambridge Univ. Press, 2006).
Gopal, R., A. Goodchild, G. Hewinson, R., de la Rua-Domenech, R. & Clifton-Hadley, R. Introduction of bovine tuberculosis from bought-in cattle in Northeast England. Vet. Record. (in the press).
Krebs, J. R. Independent Scientific Review Group Report (Ministry of Agriculture, Fisheries and Food, UK,1997).
Clifton-Hadley, R. S. et al. in Proceedings of the Society for Veterinary Epidemiology and Preventive Medicine (eds Thrusfield, M. V. & Goodall, E. A.) 15–27 (Ennis, County Clare, 1998).
Woodroffe, R. et al. Spatial association of Mycobacterium bovis infection in cattle and badgers Meles meles. J. Appl. Ecol. 42, 852–862 (2005).
Ewer, K. et al. Antigen mining with iterative genome screens identifies novel diagnostics for the Mycobacterium tuberculosis complex. Clin. Vaccine Immunol. 13, 90–97 (2006).
Cockle, P. J. et al. Identification of novel Mycobacterium tuberculosis antigens with potential as diagnostic reagents or subunit vaccine candidates by comparative genomics. Infect. Immun. 70, 6996–7003 (2002).
Inwald, J. et al. Microarray-based comparative genomics: genome plasticity in Mycobacterium bovis. Comp. Funct. Genom. 3, 342–344 (2002).
Tsolaki, A. G. et al. Functional and evolutionary genomics of Mycobacterium tuberculosis: insights from genomic deletions in 100 strains. Proc. Natl Acad. Sci. USA 101, 4865–4870 (2004).
Kremer, K. et al. Comparison of methods based on different molecular epidemiological markers for typing of Mycobacterium tuberculosis complex strains: interlaboratory study of discriminatory power and reproducibility. J. Clin. Microbiol. 37, 2607–2618 (1999).
Durr, P. A., Clifton-Hadley, R. S. & Hewinson, R. G. Molecular epidemiology of bovine tuberculosis. II. Applications of genotyping. Rev. Sci. Tech. 19, 689–701 (2000).
Kamerbeek, J. et al. Simultaneous detection and strain differentiation of Mycobacterium tuberculosis for diagnosis and epidemiology. J. Clin. Microbiol. 35, 907–914 (1997).
van Embden, J. D. et al. Genetic variation and evolutionary origin of the direct repeat locus of Mycobacterium tuberculosis complex bacteria. J. Bacteriol. 182, 2393–2401 (2000).
Groenen, P. M., Bunschoten, A. E., van Soolingen, D. & van Embden, J. D. Nature of DNA polymorphism in the direct repeat cluster of Mycobacterium tuberculosis; application for strain differentiation by a novel typing method. Mol. Microbiol. 10, 1057–1065 (1993).
Jeffreys, A. J., Wilson, V. & Thein, S. L. Individual-specific 'fingerprints' of human DNA. Nature 316, 76–79 (1985).
Monaghan, M. L., Doherty, M. L., Collins, J. D., Kazda, J. F. & Quinn, P. J. The tuberculin test. Vet. Microbiol. 40, 111–124 (1994).
Gilbert, M. et al. Cattle movements and bovine tuberculosis in Great Britain. Nature 435, 491–496 (2005).
Costello, E. et al. Study of restriction fragment length polymorphism analysis and spoligotyping for epidemiological investigation of Mycobacterium bovis infection. J. Clin. Microbiol. 37, 3217–3222 (1999).
Selander, R. K. et al. Methods of multilocus enzyme electrophoresis for bacterial population genetics and systematics. Appl. Environ. Microbiol. 51, 873–884 (1986).
Acknowledgements
We thank past and present members of the Tuberculosis Research Group, Tuberculosis Epidemiology Group and the Tuberculosis Diagnostics Group at VLA Weybridge for their data, advice and discussion, and members of the Centre for the Study of Evolution, University of Sussex, UK, for discussion and critical reading of the manuscript. In particular, we should like to thank D. Lamb for all her help. We should also like to thank our friends and colleagues from the Republic of Ireland, Northern Ireland and France for their continuing help and collaboration. Our work is funded by the Department of Environment, Food and Rural Affairs, Great Britain.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Related links
Related links
DATABASES
Entrez Genome Project
FURTHER INFORMATION
Glossary
- Recombination
-
In bacterial population genetics, recombination is the transfer of a segment of chromosomal DNA from one strain to another. Referred to as 'sex' in bacteria because recombination breaks the linkage between alleles at different loci.
- Population bottleneck
-
A severe reduction in population size that generally leads to a loss of genetic variation by population sampling. During the bottleneck, drift can further homogenize the population.
- Selective sweep
-
(Periodic selection). Process by which a new favourable mutation sweeps to fixation in a population and purges variation at, or around, the selected locus (sexual population) or for the entire chromosome (clonal population). For a clonal bacterial population the entire chromosome is taken to fixation with the driven locus (chromosomal hitch-hiking), and the only variation left in the population accumulates by mutation during the selective sweep.
- British Isles
-
The British Isles contain two states, the United Kingdom of Great Britain and Northern Ireland (referred to as the UK) and the Republic of Ireland.
- Clonal complex
-
A group of bacterial strains derived from a recent common ancestor that share many alleles at various phylogenetically informative loci. A clonal complex generally includes the ancestral genotype and strains with minor variation. This definition is highly subjective. Here, a clonal complex is defined in terms of strains bearing closely related spoligotype patterns.
- Strain
-
A single isolate of any bacterial population and any laboratory induced variants thereof. All types of the vaccine isolate BCG are considered to be a single strain even though many variants of the original isolate exist in laboratories throughout the world.
- Index of association
-
A fairly blunt tool to detect linkage disequilibrium, and therefore recombination, in a sample of allele frequencies from a population. Applied by Maynard Smith and others to show that bacterial populations can range from the panmictic to the clonal.
- Linkage disequilibrium
-
The condition in which the frequency of a particular haplotype for two loci is significantly different from that expected under random mating. For a population in linkage equilibrium the expected frequency is the product of observed allelic frequencies at each locus. For haploid bacteria if the type of allele at one locus predicts the type of allele at another locus then the loci are in linkage disequilibrium.
- Homoplasy
-
An identical mutation or similar characteristic found in phylogenetically unrelated lineages. Homoplasic mutations are not identical by descent from the common ancestor, and in bacteria can be generated by either repeated, independent mutation or by recombination.
- Variable number tandem repeat analysis
-
(VNTR). VNTR analysis of strains of the M. tuberculosis complex is a method to detect variation in the number of repeat units found at a series of chromosomally dispersed mini-satellite loci. The VNTR genotype of a strain is represented as a string of integers reflecting the number of repeats detected at each locus.
- Ecotype
-
The bacterial ecotype concept suggests that bacterial ecotypes have the following properties: they occupy distinct niches; selective sweeps limit the diversity in each ecotype; and the diversity between ecotypes is free to increase.
- Spoligotype
-
The spoligotype is determined using a PCR and hybridization method to measure allelic variation in the direct repeat region of strains of the M. tuberculosis complex.
- Clade
-
For the M. tuberculosis complex, a clade is informally used to describe the group of organisms descended from an ancestral cell without change in the major phylogenetically informative markers. A clade can contain more than one ecotype. This definition differs from the cladistic definition of a clade that would include all descendents of a recent common ancestor.
- Founder effect
-
The reduction in diversity caused by population sampling as a small group of organisms establish themselves in a new ecological niche (host) or geographical region. During the founding of the new population, selective sweeps and drift in a small population can further reduce diversity.
- Non-synonymous mutation
-
A single nucleotide mutation in a coding region that alters the encoded amino acid. By contrast, a synonymous mutation does not result in an amino-acid replacement.
- Great Britain
-
Collectively, England, Scotland and Wales are known as Great Britain.
- Single intradermal comparative cervical test
-
(SICCT). Also known as the tuberculin test, SICCT is an immunological method used to detect cattle infected with M. bovis, and is an integral part of the 'test and slaughter' protocol.
- Pasteurization
-
A method of heating food to reduce the number of pathogenic organisms present. Pasteurization of milk is the major barrier to the transmission of bovine tuberculosis from cattle to humans.
- Multilocus sequence typing
-
A portable and easier-to-use replacement for multilocus enzyme electrophoresis (MLEE) for identifying genotypic variation in prokaryotic populations. Multilocus sequence typing identifies allelic mismatches in the nucleotide sequence of a small number of housekeeping genes to identify sequence types.
- Wahlund effect
-
The increase in heterozygocity observed after the mixing of two previously isolated sexual eukaryotic populations. In a similar manner, for bacterial populations the observed allelic diversity of a locus can be artificially inflated if a population sample contains strains from two populations that are geographically or phylogenetically separated.
Rights and permissions
About this article
Cite this article
Smith, N., Gordon, S., de la Rua-Domenech, R. et al. Bottlenecks and broomsticks: the molecular evolution of Mycobacterium bovis. Nat Rev Microbiol 4, 670–681 (2006). https://doi.org/10.1038/nrmicro1472
Issue Date:
DOI: https://doi.org/10.1038/nrmicro1472
This article is cited by
-
The devil you know and the devil you don’t: current status and challenges of bovine tuberculosis eradication in the United States
Irish Veterinary Journal (2023)
-
Phylogenetic analysis of prospective M. bovis antigens with the aim of developing candidate vaccines for bovine tuberculosis
Journal of Genetic Engineering and Biotechnology (2023)
-
Genome-wide estimation of recombination, mutation and positive selection enlightens diversification drivers of Mycobacterium bovis
Scientific Reports (2021)
-
Long-term molecular surveillance provides clues on a cattle origin for Mycobacterium bovis in Portugal
Scientific Reports (2020)
-
Chance and pleiotropy dominate genetic diversity in complex bacterial environments
Nature Microbiology (2019)