Mathov, YoavNissim Rafinia, MalkaLeibson, ChenGalun, NirMarquès i Bonet, Tomàs, 1975-Kandel, AryeLiebergal, MeirMeshorer, EranCarmel, Liran2025-01-152025-01-152024Mathov Y, Nissim-Rafinia M, Leibson C, Galun N, Marques-Bonet T, Kandel A, et al. Inferring DNA methylation in non-skeletal tissues of ancient specimens. Nat Ecol Evol. 2024 Nov 20. DOI: 10.1038/s41559-024-02571-w2397-334Xhttp://hdl.handle.net/10230/69133Data de publicació eelctrònica: 20-11-2024Genome-wide premortem DNA methylation patterns can be computationally reconstructed from high-coverage DNA sequences of ancient samples. Because DNA methylation is more conserved across species than across tissues, and ancient DNA is typically extracted from bones and teeth, previous works utilizing ancient DNA methylation maps focused on studying evolutionary changes in the skeletal system. Here we suggest that DNA methylation patterns in one tissue may, under certain conditions, be informative on DNA methylation patterns in other tissues of the same individual. Using the fact that tissue-specific DNA methylation builds up during embryonic development, we identified the conditions that allow for such cross-tissue inference and devised an algorithm that carries it out. We trained the algorithm on methylation data from extant species and reached high precisions of up to 0.92 for validation datasets. We then used the algorithm on archaic humans, and identified more than 1,850 positions for which we were able to observe differential DNA methylation in prefrontal cortex neurons. These positions are linked to hundreds of genes, many of which are involved in neural functions such as structural and developmental processes. Six positions are located in the neuroblastoma breaking point family (NBPF) gene family, which probably played a role in human brain evolution. The algorithm we present here allows for the examination of epigenetic changes in tissues and cell types that are absent from the palaeontological record, and therefore provides new ways to study the evolutionary impacts of epigenetic changes.application/pdfeng© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41559-024-02571-wEpigeneticsEpigenomicsEvolutionary geneticsinfo:eu-repo/semantics/openAccess