An international research team led by Henrik Kaessmann from Heidelberg University and Stein Aerts from Leuven University mapped the activity of genetic control elements in individual cells of the developing cerebellum of four primate species, mice, and marsupials. Based on this, advanced AI models were developed and validated to predict the activity of these control elements based solely on their DNA sequence.
Genetic control elements determine where and when genes are activated. They play a central role in evolutionary innovations, such as brain enlargement. The cerebellum, which is not only responsible for movement and balance but also plays a role in cognition, emotion, and language, has developed particularly strongly in the course of human evolution. The researchers were able to trace the evolutionary changes and identify specific elements that are crucial for the development of the human cerebellum.
A significant finding: a new activating control element near the gene THRB, which codes for a receptor of a thyroid hormone. The activation of THRB in the precursor cells of the human cerebellum has probably contributed to the significant enlargement of the human cerebellum.
The study, which also involved researchers from the DPZ as well as from Leipzig, Hungary, and the UK, was published in the journal Science. It shows how advanced AI, in combination with genomic and embryological analyses, can revolutionize research into complex biological processes and contribute to our understanding of what distinguishes humans from non-human primates.
Original publication
I. Sarropoulos, M. Sepp, T. Yamada, P.S.L. Schäfer, N. Trost, J. Schmidt, C. Schneider, C. Drummer, S. Mißbach, I.I. Taskiran, N. Hecker, C. Bravo González-Blas, R. Frömel, P. Joshi, E. Leushkin, F. Arnskötter, K. Leiss, K. Okonechnikov, S. Lisgo, M. Palkovits, S. Pääbo, M. Cardoso-Moreira, L.M. Kutscher, R. Behr, S.M. Pfister, S. Aerts, and H. Kaessmann: The evolution of gene regulation in mammalian cerebellum development. Science (published online 29.01.2026), DOI: 10.1126/science.adw9154
