Open PhD position

Are you fascinated by evolution, health, and ancient DNA?
Do you want to contribute to cutting-edge research with real-world implications?
Join our Lab!

A PhD position is available, supported by the FutureData4EU program

Detailed information on the PhD program and application process: HERE

Evolutionary perspective on health and medicine through the lens of paleogenomics

Disentangling the history of human biological adaptation has fascinated scientists for more than a century. How did humans evolve in response to the new environments they encountered while expanding from Africa? How ancient human populations responded genetically to cultural changes such as the dietary shifts associated with the onset of agriculture? Do our past adaptations have consequences for health and medicine today?

Since 2010, advancements and the subsequent broad applications of next-generation sequencing techniqueshave enabled rapid and cost-effective sequencing of eukaryotic genomes and paved the way for a genomic era in the field of ancient DNA, which is now established as a new discipline, called Paleogenomics. Ancient DNA provides a glimpse into the genetic history of humans across the globe over the past millennia. The study of paleogenomic data made it possible to examine the deep past of human populations, and to explore the genetic makeup and adaptation dynamics of archaic lineages and of ancient and present-day populations. The sequencing of Neanderthal and Denisovan genomes has revealed a complex history of admixture between archaic humans and the ancestors of modern humans. Consequently, archaic sequences became part of the modern human gene pool, possibly influencing life and health of our ancestors, as well as of living individuals. For example, lines of evidence suggest that genetic variants introgressed from archaic hominins may have affected genes associated with immunity, or pharmacogenes - genes involved in drug metabolism - as these genes can relate to changing environments, and beneficial variants may have been positively selected by modern humans. In addition, modern human population dynamics had a pivotal role in shaping the current pattern of genomic diversity. Within the past 10,000 years, we observed two main genetic turnovers in Europe, namely the Neolithic transition and the expansion of farming communities from Anatolia, and the migration from Pontic-Caspian Steppe during Bronze Age. These population dispersals, changing lifestyle and higher population density, may have resulted in increased transmission of pathogens, driving selection of variants in immune response genes, and triggered important changes in the adaptive evolution of our species both at local and global scales. While the availability of thousands of ancient genomes gives us the opportunity to unveil the history of human adaptation at unprecedented depth and precision, the study of the contribution of archaic and ancient alleles to current human health is still in its infancy. Shedding light on adaptive evolutionary dynamics of our species would promote a more comprehensive reconstruction of our past, sharpening the current understanding of our present. The results of this project will pioneer the field of Evolutionary Medicine, thus providing significant contributions to biomedical research and medical applications.

Possible sub-themes

The availability of thousands of high-quality ancient genomes can help the identification of rare variants introgressed from archaic and ancient humans into the modern populations to address key questions related to human health and disease. Studies on modern humans shown that differential outcomes after infection are due to specific DNA mutations that alter host defense mechanisms. However, little is known about adaptation of archaic and ancient humans to past environments and pathogens. Therefore, studying genetic variants associated with infectious-disease risks in fossil remains, highlight the potential value of paleogenomics in medicine. Recent studies pointed out the value of using ancient DNA to reconstruct the evolutionary history of immune disorders and past epidemics. Kerner et al. (2021) found a tuberculosis risk variant in ancient genomes that has evolved under strong negative selection over the past two millennia, probably reflective of the pressure imposed by Mycobacterium tuberculosis. Ancient DNA can also be used to identify advantageous mutations that are positively selected over time through pathogen exposure. For example, some immunity-related genes under positive selection have been found to be associated with the Neolithic transition in Europe. This is the case for IL1R2, for which high levels of expression are associated with protection against several autoimmune disorders.

Lastly, the study of genetic variants inherited from the admixture between modern and archaic humans can help us to disentangle adaptation processes to new environments and host resistance to pathogens. An example is the adaptation of Tibetan populations to high altitudes due to the introgression of adaptive alleles

• Legacy of archaic humans
• Immune disorders
• Adaptation to pathogens
• Co-evolution pathogens-host

Supervisor