Algorithm predicts DNA methylation in ancient specimens, providing insight into human evolution

Research published in Nature Ecology & Evolution 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, led by Ph.D. 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), applied their method to the brain, offering a deeper understanding of the evolutionary processes that shaped the human brain and neural functions. The findings could transform how we study the evolution of human complex traits.

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 also be 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.