Infektionsresistenz gegen Cholera und Pest als Selektionsfaktor menschlicher Evolution
Final Report Abstract
Recent evolution under selective pressure was supposed for several polymorphisms of the human genome in Europe. Among others, lactase persistence and light skin pigmentation are considered to have developed and reached high frequencies in prehistoric times. By analyzing for the presence of the mutations in about 40 prehistoric individuals we could confirm these hypotheses. On the same samples we could also estimate the age of other mutations which are supposed to have been positive selected in Europe during epidemics of the past. Among these, we investigated mutations responsible for cystic fibrosis, for hemochromatosis and for favism. Moreover, we produced data for the mutations of the genes CCR5 and CCR2. Since all of these were proposed to be positively selected by plague, we tested the hypothesis on about 170 victims of the historical pestilences collected from different parts of Europe. The only exception was cystic fibrosis, a deadly recessive disorder which was proposed to have been positively selected by intestinal infectious diseases. We could confirm that the principal mutations for cystic fibrosis, the Delta F508, arose more than 3000 years ago in North Europe. Its frequency in Europe can be explained by a balanced polymorphism, but we could not corroborate the hypothesis that intestinal infections were the driving force of this process by analyzing cholera victims of the past. For the purpose of this investigation we developed a new multilocus analysis based on multiplex PCR and suitable for different detecting methods, like minisequencing, Singer’s sequencing and NGS (next Generation Sequencing). Besides the mutations cited, five high polymorphic neutral SNPs and the homologous gene Amelogenin were amplified simultaneously. The presence of these SNPs enables the detection of potential contaminant DNA coming from the environment or from cross-contamination. A major point of the project was to determine the actual cause of death in putative plague victims. Mass graves of medieval times could have had different causes and the diagnosis of “putative plague pits” was not enough to test on those skeletal individuals the hypotheses of resistance against the . Thus, in an early phase of the project, we needed to test for the presence of ancient DNA of the bacterium Yersinia pestis in the putative plague victims. We could assert without doubts the presence of Y. pestis in 5 mass graves by analyzing diagnostic markers. Moreover, by studying several neutral SNPs we could place the different strains on a phylogenetic tree and show that they were ancestral to circulating populations. The results of this investigation are already partially published in peer-reviewed scientific journals. A number of papers is in preparation. The project and the results of the research were publicized in numerous popular media worldwide, including international television, radio and documentary-films.
Publications
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Absence of the Lactase-Persistence associated allele in early Neolithic Europeans. Proc Nat Acad Sci. 2007, 104,10: 3736-3741
Burger J, Kirchner M, Bramanti B, Haak W, Thomas MG
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Plague and beyond. 37th Symposium on Archaeometry. Siena, Italy, 13.-16.05.2008
Bramanti B, Hänsch S, Bogus M, Bianucci R, Ottoni C, Donath A
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Distinct clones of Y. pestis caused the Black Death. Congress of the Paleopathological Association. Vienna, Austria, 23.- 26.08.2010
Hänsch S, Bramanti B et al.
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Distinct Clones of Yersinia pestis Caused the Black Death. PLoS Pathog. 2010, 6,10: e1001134
Haensch S, Bianucci R, Signoli M, Rajerison M, Schultz M, Kacki S, Vermunt M, Weston DA, Hurst D, Achtman M, Carniel E, Bramanti B
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The causative agent(s) of the Black Death. 10th International Symposium on Yersinia, Recife, Brasil 23-27.10.2010
Bramanti B, Hänsch S, Carniel E. et al.
