Ancient DNA investigation into infectious diseases of medieval Europe

Infectious diseases have been a burden to human populations around the globe, posing an immense selective pressure on our genomes. Moreover, the constant evolution of pathogens poses a major threat to human health. In my dissertation, I applied ancient genomics to investigate the pathogen diversity and infectious disease burden in medieval Europe as well as to identify Human Leukocyte Antigens (HLA) alleles involved in predisposition to infections. In chapter 1, I identified the HLA-DRB1*03 as a risk factor for Salmonella infection in medieval Europeans. In the case-control association study between HLA alleles and medieval leprosy (chapter 2), I reported five alleles linked to leprosy predisposition in Europeans. The pathogen screening of the early medieval settlement in chapter 3 allowed me to estimate the infection prevalence at the time (~ 31.4%). Seven genomes belonging to four pathogen species (Mycobacterium leprae, variola virus, parvovirus B19 and hepatitis B virus) were reconstructed and analyzed. In chapter 4, the genomic analysis of medieval Yersinia pestis strains revealed the depletion of the virulence-associated pla gene exclusively in isolates dating to the end of the Medieval pandemic. In the following chapter 5, I demonstrated that only a subset of modern strains carried a phage encoding the zonula occludens toxin– a known virulence factor. The phage-positive strains were associated with a wide geographic spread and a large proportion of human infections. In chapter 6, I provided evidence that plague victims were not exclusively buried in mass graves in medieval Denmark, but also at parish cemeteries. The findings presented in my dissertation contribute to a better understanding of the host-pathogen coevolution and the genetic implications of past epidemics on our health today.

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