Genetic legacy of earlier epidemics

Professor Ben Krause-Kyora researches the epidemics of our ancestors by analysing ancient DNA. His findings also help to improve our understanding of today’s inflammatory diseases.

Jaw bones of a human
© Dominik Göldner, BGAEU, Berlin

Jaw bones of the man buried around 5,000 years ago in Riņņukalns, Latvia. The research team found remains of the genetic material of the pathogen that causes the plague in this material.

A piece of the skull or a tooth from old skeletons is all Professor Ben Krause-Kyora needs to obtain the DNA, i.e. the carrier of genetic information. DNA that is around 100 years old or older is called ancient DNA or aDNA. The material that the archaeologist and biochemist at the Institute of Clinical Molecular Biology (IKMB) at Kiel University works with is significantly older than that. “Our skeletons date from the Middle Ages or are even several thousand years old,” stressed Krause-Kyora. As only very little DNA is still present in such old bones, preparation of the material requires particular care. It is especially important to avoid any contamination with modern DNA. “Our rooms at the UKSH campus in Kiel are comparable to the clean rooms used for computer chip production. We make sure that everything is really DNA-free. In order to avoid any contamination, we also wear disposable suits, face masks, hair covers and gloves,” explained Krause-Kyora, who is also a member of the Cluster of Excellence “Precision Medicine in Chronic Inflammation” (PMI). Once the DNA has been isolated from the sample, it is analysed using the same high throughput sequencing equipment as modern DNA.

From this analysis we are able to establish how people lived thousands of years ago, for example, and who was related to whom. We can then draw conclusions about social structures or migrations of people. Krause-Kyora is particularly interested in research questions at the interface between archaeology and medicine. “On the one hand, I am trying to detect pathogens in historic and prehistoric samples and trace their evolutionary history. On the other hand, I am interested in determining the kind of footprint that these pathogens have left behind in our genome.”

This research has led to many significant discoveries. For example, the oldest ever evidence of the pathogen that causes the plague (Yersinia pestis) was found on a skeleton that is approximately 5,000 years old. “This is very close to the point in time when the original soil bacterium passed to people and became a pathogen. Understanding how a normal soil bacterium that is actually present everywhere looks for a new host, specialises in this host and over the long term becomes a deadly bacterium, as happened in the Middle Ages, is impressive in itself.” In comparison with samples of plague victims from the Middle Ages, the aDNA expert was able to demonstrate that the bacterium also mutated and adapted to changing conditions in epidemic outbreaks.

Another discovery made by Krause-Kyora’s working group was that the infectious disease leprosy left traces behind in the human genome of Europeans. In a study, they compared aDNA of skeletons from a leprosy hospital with aDNA of people without leprosy as well as with modern DNA. They discovered that a certain variant of a gene that is vital to the body’s immune response made people more susceptible to leprosy. As lepers were isolated and could not reproduce owing to their disease, they did not pass on this risk factor. Over the long term, therefore, the gene variant prevailed and led to better defence against infectious diseases. Interestingly, this gene variant is now linked to the occurrence of inflammatory diseases of the bowel (ulcerative colitis), for example.

This shows how researching ancient human DNA can also improve our understanding of modern diseases. Whilst in earlier centuries infections made strong demands on people’s immune systems because of their living conditions, it is defective immune responses that are often the cause of chronic inflammatory diseases today. There could be an evolutionary connection to this. “We need a better understanding of modern disorders of the immune system and their historic origins in order to develop new preventive care strategies. We want to know more about the causes of diseases that made particular demands on the human immune system in earlier times and have shaped people today. For this reason, their research has been an important element of the Cluster of Excellence PMI for a long time now,” said Cluster spokesperson Professor Stefan Schreiber, the Director of the IKMB and Director of the Department of Internal Medicine I at the University Medical Center Schleswig-Holstein (UKSH), Campus Kiel.

Author: Kerstin Nees