This research introduces a novel method for inferring DNA methylation patterns in non-skeletal tissues from ancient specimens, providing new insights into human evolution. As DNA methylation is a key marker of gene expression, this work allows scientists to explore changes in gene activity in the brain and other tissues that are typically absent from the fossil record. The team applied their method to the brain, offering a deeper understanding of the evolutionary processes that shaped human brain and neural functions. The findings could transform how we study the evolution of human complex traits.
Led by PhD student Yoav Mathov under the guidance of Prof. Liran Carmel and Prof. Eran Meshorer at the Department of Genetics, Institute of Life Sciences and the Edmond & Lily Safra Center for Brain Sciences (ELSC), this research, published in Nature Ecology & Evolution, reveals a way to identify changes in DNA methylation patterns of non-skeletal tissue using ancient DNA sequences.
Unlike previous studies that focused on skeletal tissue—usually the only source of ancient human DNA—this new approach utilizes developmental patterns of DNA methylation to infer skeletal changes in DNA methylation that would be also observed in other tissues. By training an algorithm on methylation data from living species, the team achieved up to 92% precision in predicting DNA methylation across various tissues.
Their algorithm was then applied to ancient humans, revealing over 1,850 sites of differential methylation specifically in prefrontal cortex neurons. Many of these sites are linked to genes crucial for brain development, including the neuroblastoma breakpoint family (NBPF), which has long been associated with human brain evolution.
“The ability to analyze ancient DNA methylation patterns beyond bones gives us a window into how tissues, especially brain cells, have evolved epigenetically over time,” said Mathov. “This could lead to a deeper understanding of the evolutionary forces that shaped the human brain and other vital organs.”
This innovative tool expands the horizons of evolutionary biology and anthropology, allowing scientists to investigate tissue-specific epigenetic changes that are not preserved in fossils. The study paves the way for new insights into the role of epigenetic changes in human evolution and the development of complex neural functions.
The research paper titled “Inferring DNA methylation in non-skeletal tissues of ancient specimens” is now available in Nature Ecology & Evolution can be accessed at https://www.nature.com/articles/s41559-024-02571-w
DOI 10.1038/s41559-024-02571-w
Researchers:
Yoav Mathov1,2, Malka Nissim-Rafinia1, Chen Leibson1, Nir Galun1, Tomas Marques-Bonet3-6, Arye Kandel7, Meir Liebergal7, Eran Meshorer1,2, Liran Carmel1
Institutions:
1 Department of Genetics, The Alexander Silberman Institute of Life Sciences, Faculty of Science, the Hebrew University of Jerusalem
2 Edmond and Lily Safra Center for Brain Sciences (ELSC), the Hebrew University of Jerusalem
3 Institute of Evolutionary Biology (UPF-CSIC)
4 Catalan Institution of Research and Advanced Studies (ICREA)
5 CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)
6 Institut Català de Paleontologia Miquel Crusafont, Universitat Autònoma de Barcelona, Edifici ICTA-ICP, c/ Columnes s/n
7 Orthopedic Department, Hadassah – Hebrew University Medical Center, Jerusalem
The Hebrew University of Jerusalem is Israel’s premier academic and research institution. With over 23,000 students from 90 countries, it is a hub for advancing scientific knowledge and holds a significant role in Israel’s civilian scientific research output, accounting for nearly 40% of it and has registered over 11,000 patents. The university’s faculty and alumni have earned eight Nobel Prizes, two Turing Awards a Fields Medal, underscoring their contributions to ground-breaking discoveries. In the global arena, the Hebrew University ranks 81th according to the Shanghai Ranking. To learn more about the university’s academic programs, research initiatives, and achievements, visit the official website at http://new.huji.ac.il/en