title: Ancient DNA analysis - An established technique in charting the evolution of tuberculosis and leprosy.
abstract: Many tuberculosis and leprosy infections are latent or paucibacillary, suggesting a long time-scale for host and pathogen co-existence. Palaeopathology enables recognition of archaeological cases and PCR detects pathogen ancient DNA (aDNA). Mycobacterium tuberculosis and Mycobacterium leprae cell wall lipids are more stable than aDNA and restrict permeability, thereby possibly aiding long-term persistence of pathogen aDNA. Amplification of aDNA, using specific PCR primers designed for short fragments and linked to fluorescent probes, gives good results, especially when designed to target multi-copy loci. Such studies have confirmed tuberculosis and leprosy, including co-infections. Many tuberculosis cases have non-specific or no visible skeletal pathology, consistent with the natural history of this disease. M. tuberculosis and M. leprae are obligate parasites, closely associated with their human host following recent clonal distribution. Therefore genotyping based on single nucleotide polymorphisms (SNPs) can indicate their origins, spread and phylogeny. Knowledge of extant genetic lineages at particular times in past human populations can be obtained from well-preserved specimens where molecular typing is possible, using deletion analysis, microsatellite analysis and whole genome sequencing. Such studies have identified non-bovine tuberculosis from a Pleistocene bison from 17,500 years BP, human tuberculosis from 9000 years ago and leprosy from over 2000 years ago.
authors.affiliation: Centre for Clinical Microbiology, Division of Infection & Immunity, University College London, London, UK; Centre for the History of Medicine, Division of Biosciences, University College London, UK. Electronic address: h.donoghue@ucl.ac.uk.
authors.forename: Helen D
authors.initials: HD
authors.lastname: Donoghue
authors.affiliation: Centre for Clinical Microbiology, Division of Infection & Immunity, University College London, London, UK; Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: spigelman@btinternet.com.
authors.forename: Mark
authors.initials: M
authors.lastname: Spigelman
authors.affiliation: Centre for Clinical Microbiology, Division of Infection & Immunity, University College London, London, UK. Electronic address: Justin.OGrady@uea.ac.uk.
authors.forename: Justin
authors.initials: J
authors.lastname: O'Grady
authors.affiliation: Department of Anthropology, Hungarian Natural Science Museum, Budapest, Hungary. Electronic address: szikossy@nhmus.hu.
authors.forename: Ildikó
authors.initials: I
authors.lastname: Szikossy
authors.affiliation: Department of Anthropology, Hungarian Natural Science Museum, Budapest, Hungary. Electronic address: papildi@hotmail.com.
authors.forename: Ildikó
authors.initials: I
authors.lastname: Pap
authors.affiliation: Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Edgbaston, Birmingham, UK. Electronic address: o.y.lee@bham.ac.uk.
authors.forename: Oona Y-C
authors.initials: OY
authors.lastname: Lee
authors.affiliation: Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Edgbaston, Birmingham, UK. Electronic address: h.wu.2@bham.ac.uk.
authors.forename: Houdini H T
authors.initials: HH
authors.lastname: Wu
authors.affiliation: Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Edgbaston, Birmingham, UK. Electronic address: g.besra@bham.ac.uk.
authors.forename: Gurdyal S
authors.initials: GS
authors.lastname: Besra
authors.affiliation: Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Edgbaston, Birmingham, UK. Electronic address: d.e.minnikin@bham.ac.uk.
authors.forename: David E
authors.initials: DE
authors.lastname: Minnikin
mesh_terms: D015373:Bacterial Typing Techniques; D060085:Coinfection / Q000150:complications / Q000235:genetics / Q000266:history; D004269:DNA, Bacterial / Q000032:analysis* / Q000235:genetics; D019143:Evolution, Molecular; D016680:Genome, Bacterial; D049690:History, Ancient; D006801:Humans; D007918:Leprosy / Q000150:complications / Q000235:genetics* / Q000266:history; D058889:Molecular Typing / Q000379:methods; D009166:Mycobacterium leprae / Q000235:genetics*; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D021141:Nucleic Acid Amplification Techniques; D010164:Paleopathology / Q000379:methods; D016133:Polymerase Chain Reaction; D014376:Tuberculosis / Q000150:complications / Q000235:genetics* / Q000266:history
chemical_list: D004269:DNA, Bacterial
keywords: Ancient DNA; Evolution; Molecular typing; Mycobacterium leprae; Mycobacterium tuberculosis