Burger/Barau/Ketting
Identifying recent episodes of adaptation in humans by genome and epigenome editing
Supervisor: Joachim Burger
Co-Supervisor: Joan Barau, René Ketting
Scientific Background
The history of Europeans in the last millennia has brought several significant changes in environmental conditions. The most significant is the transition from a hunter-gatherer subsistence to a sedentary farming lifestyle. Subsequently, there have been other incursions, primarily the spread of zoonotic and new infectious diseases.
Epigenetic markers associated with gene regulation are suspected to respond more rapidly to new selection pressures than genetic mutations (e.g. Raj et al. 2013). Although their function is not always fully understood, their association with genes and pathways may serve as a starting point to identify genomic regions and traits that have played adaptive roles in human populations in a short period of time.
In a previous project we have identified differentially methylated regions and associated genetic variants in genomes of humans with different life-styles. We suspect that they have been positively selected in recent time periods and now want to shed light on their functional background.
Project description
Exploring recent human selection is an exciting area of study. This PhD project seeks to determine whether significant selective processes have occurred in humans over the last millennia, and which genes and markers are involved. Genetic mutations tend to establish slowly in human populations, even if advantageous, whereas epigenetic variants may spread more quickly. We have pinpointed several hundred potential epigenetic variants. The goal of this PhD research is to uncover their functions and assess their evolutionary advantages in different human groups. The candidate will use CRISPR-Cas genome and epigenome editing to modify human cell lines in the lab, recapitulating patterns of association between genetic and epigenetic variants. These will be analyzed based on their effects on genome regulation and gene expression. Thus, most of the research will be lab-based, involving cell culture work, genome and epigenome editing, and expression analysis. Subsequent genomic and epigenomic data evaluation and related analyses will be conducted in collaboration with a bioinformatics team.
What you will learn
The PhD student will gain hands-on experience in molecular laboratory techniques with cell cultures and cutting-edge genome and epigenome editing methods. Additionally, the student will acquire foundational knowledge in genomics, epigenomics, and bioinformatics, skills that are highly valuable in today's job market.
Your qualifications
We expect the candidate to have a solid background in molecular biology and cell biology, as well as an interest in human evolution. Computer skills are advantageous.
Publications relevant to this project
Xia B, Zhang W, Zhao G, Zhang X, Bai J, Brosh R, Wudzinska A, Huang E, Ashe H, Ellis G, Pour M, Zhao Y, Coelho C, Zhu Y, Miller A, Dasen JS, Maurano MT, Kim SY, Boeke JD, Yanai I (2024) On the genetic basis of tail-loss evolution in humans and apes Nature. 626 (8001):1042-1048. https://doi.org/10.1038/s41586-024-07095-8
Burger J, Link V, Blöcher J, Schulz A, Sell C, Pochon Z, Diekmann Y, Žegarac A, Hofmanová Z, Winkelbach L, Reyna-Blanco CS, Bieker V, Orschiedt J, Brinker U, Scheu A, Leuenberger C, Bertino TS, Bollongino R, Lidke G, Stefanović S, Jantzen D, Kaiser E, Terberger T, Thomas MG, Veeramah KR, Wegmann D. Low Prevalence of Lactase Persistence in Bronze Age Europe Indicates Ongoing Strong Selection over the Last 3,000 Years (2020) Curr Biol. 30(21):4307-4315.e13. https://doi.org/10.1016/j.cub.2020.08.033
Kungulovski G, Jeltsch A (2016) Epigenome Editing: State of the Art, Concepts, and Perspectives. Trends Genet. 32(2):101-113. https://doi.org/10.1016/j.tig.2015.12.001