Bouwman, Abigail

Rühli, Frank

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PERSPECTIVEAdvances in ancient DNA research can help radiologicalinterpretations of archaeological diseasesAbigail Bouwman & Frank RühliReceived: 9 December 2012 /Accepted: 16 December 2012 /Published online: 12 January 2013# ISS 2013Evolutionary medicine explores among other things the hu-man vulnerability towards pathogens. To increase the diag-nostic level of evidence, alongside radiological investigations,molecular techniques (such as ancient DNA analyses) areoften being applied.Ancient DNA (aDNA) is DNA recovered from archaeo-logical and historical specimens. This DNA is highly de-graded and fragmented by biological and environmentalfactors and is therefore difficult to analyse. However,sequences retrieved from ancient material are highly usefulin many ways, including for medical purposes.The first aDNA experiment was conducted in 1984 todetermine the biological classification of the extinct quagga,revealed to be a close relative of the zebra [1]. In the 1980s and1990s there were multiple publications in which the authorsclaimed to have extracted aDNA from a variety of samples.However, some of these sequences were later determined to bethe result of modern contamination. This led to the introduc-tion of vigorous anti-contamination procedures in the field ofaDNA research. At this time a greater understanding of theneed for hypothesis-led research allowed for a great diversityof targets. Ancient DNA has been used extensively, for exam-ple, to clarify the domestication events of animals and plants,to understand the movements of humans, and to examine thehistory of modern and ancient disease.Among the first pathogens targeted by ancient DNAresearchers were the Mycobacterium tuberculosis complex(MTBC) organisms, and this DNA has been proven to be oneof the most robust of all the pathogens studied in archaeologicalremains. Tuberculosis is a chronic infection caused by any ofthe members of the MTBC, which are very similar genetically.Tuberculosis can cause numerous bone changes, most signifi-cantly in Pott’s disease, where the vertebrae are pitted andgradually undergo extensive osteoblastic activity, resulting inspinal collapse, and cause a hunched posture. Whilst tubercu-losis can be inferred from visual (including radiological) in-spection of archaeological remains, bone changes only occur ina minority of cases. In addition, the actual causative bacteriacannot be known without microbiological testing.Many groups have amplified and sequenced archaeologicalMTBC DNA, and increasingly try to identify the members ofthe complex; strain identification is easier than type identifi-cation as less genetic information is required. Interestingly, sofar, only one archaeological tuberculosis case has been shownto have been caused by the Mycobacterium bovis strain,despite the close bovine–human habitation of the past.Modern geneticists are increasingly studying the phylo-geography of the MTBC, i.e. the correlation between thestrain and its location. This involves examining multiplemutations from one sample. Traditional polymerase chainreaction (PCR) methods work by targeting specific DNAusing primers (short pieces of nucleotides that attach to thecomplimentary sequence) and copying the DNA in-between. The DNA is then sequenced in a separate experi-ment. Multiple primers can be used in one reaction, butgenerally this only amplifies a few targets, resulting in upto only a few thousand bases of DNA from a limited numberof sequences. Therefore, it is highly unlikely that enoughinformative information could be gathered from one degrad-ed archaeological sample to properly place an ancient bac-terium into a phylogeographic type.Recently introduced into the research field of aDNA stud-ies, next generation sequencing (NGS) works by taking theDNA and adding short sequences to either end that are com-plimentary to universal primers, eliminating the specificity ofconventional PCR. Each piece of DNA is then amplified andsequenced individually, so that thousands of strands can beA. Bouwman : F. Rühli (*)Centre for Evolutionary Medicine, Institute of Anatomy,University of Zurich, Winterthurerstrasse 190,8057 Zürich, Switzerlande-mail: frank.ruhli@anatom.uzh.chSkeletal Radiol (2013) 42:751–752DOI 10.1007/s00256-012-1568-1analysed simultaneously (see Mardis [2] for an overview).Therefore, the development of NGS systems allows forthousands of targets and millions of bases to be sequenced atonce.Using one of these NGS systems (SOLiD), MTBC DNAfrom a 19th century British individual has been typed andidentified as a similar, but different type from that isolated inNorth America in 1905, known as H37Rv [3]. One hundredother individuals from the last 2,000 years across Europe arestill being analysed; the bone changes and strain identificationare being compared to see if there is any correlation betweenthe strain and the pathology.Next-generation sequencing has opened up a new field ofresearch to the evolutionary medicine investigator and willcontinue—alongside radiological diagnostics—to expand ourunderstanding of our past and present health.Acknowledgment The authors acknowledge funding by the MäxiFoundation, Zurich.Conflict of interest None.References1. Higuchi R, Bowman B, Freiberger M, Ryder OA, Wilson AC. DNAsequences from the quagga, an extinct member of the horse family.Nature. 1984;312:282–4.2. Mardis ER. Next-generation DNA sequencing methods. Annu RevGenomics Hum Genet. 2008;9:387–402.3. Bouwman AS, Kennedy SL, Müller R, et al. Genotype of a historicstrain of Mycobacterium tuberculosis. Proc Natl Acad Sci U S A.2012;109:18511–6.752 Skeletal Radiol (2013) 42:751–752

Advances in ancient DNA research can help radiological interpretations of archaeological diseases

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Advances in ancient DNA research can help radiological interpretations of archaeological diseases

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