Inferring DNA methylation in non-skeletal tissues of ancient specimens
Mathov, Yoav (The Hebrew University of Jerusalem)
Nissim-Rafinia, Malka (The Hebrew University of Jerusalem. Department of Genetics)
Leibson, Chen (The Hebrew University of Jerusalem. Department of Genetics)
Galun, Nir (The Hebrew University of Jerusalem. Department of Genetics)
Marquès i Bonet, Tomàs 1975- (Institut Català de Paleontologia Miquel Crusafont)
Kandel, Arye (Hebrew University Medical Center. Orthopedic Department)
Liebergal, Meir (Hebrew University Medical Center. Orthopedic Department)
Meshorer, Eran (The Hebrew University of Jerusalem. Department of Genetics)
Carmel, Liran (The Hebrew University of Jerusalem. Department of Genetics)

Data:	2024
Resum:	Genome-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.
Ajuts:	European Commission 864203 Agencia Estatal de Investigación PID2021-126004NB-100 Agencia Estatal de Investigación CEX2018-000792-M Agència de Gestió d'Ajuts Universitaris i de Recerca 2021/SGR-00177
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Nature ecology & evolution, Vol. 9 (November 2024) , p. 153-165, ISSN 2397-334X

DOI: 10.1038/s41559-024-02571-w
PMID: 39567757

24 p, 6.3 MB

El registre apareix a les col·leccions:
Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències > Institut Català de Paleontologia Miquel Crusafont (ICP)
Articles > Articles de recerca
Articles > Articles publicats