A Post-Mortem Molecular Damage Profile in the Ancient Human Mitochondrial DNA
Cuesta-Aguirre, Daniel R. (Universitat Autònoma de Barcelona. Departament de Biologia Animal, de Biologia Vegetal i d'Ecologia)
Amor Jimenez, Cristina (Centre de Recerca Ecològica i d'Aplicacions Forestals)
Malgosa Morera, Assumpció (Universitat Autònoma de Barcelona. Departament de Biologia Animal, de Biologia Vegetal i d'Ecologia)
Pereira dos Santos, Cristina Maria (Universitat Autònoma de Barcelona. Departament de Biologia Animal, de Biologia Vegetal i d'Ecologia)

Date:	2025
Abstract:	Mitochondrial DNA (mtDNA) analysis is crucial for understanding human population structure and genetic diversity. However, post-mortem DNA damage poses challenges, that make analysis difficult. DNA preservation is affected by environmental conditions which, among other factors, complicates the differentiation of endogenous variants from artefacts in ancient mtDNA mix profiles. This study aims to develop a molecular damage profile for ancient mtDNA that can become a useful tool in analysing mtDNA from ancient remains. A dataset of 427 whole genomes or capture of mtDNA sequences from individuals representing different historical periods and climatic regions was compiled from the ENA database. Present-day and UDG-treated ancient samples were also included and used to establish levels of damaged reads. Results indicated that samples from cold regions exhibited the lowest percentage of damaged reads, followed by arid, cold, tropical and temperate regions, with significant differences observed between cold and temperate regions. A global damage profile was generated, identifying 2933 positions (25% of the positions considered) with damage in more than 23. 8% of the samples analysed, deemed as damage hotspots. Notably, 2856 of these hotspots had never been reported as damage or mutational hotspots, or heteroplasmic positions. Damage hotspot frequency by position was slightly higher in the non-coding region compared with the coding region. In conclusion, this study provides a molecular damage profile for ancient mtDNA analysis that is expected to be a valuable tool in the interpretation of mtDNA variation in ancient samples.
Grants:	Agencia Estatal de Investigación PGC2018-096666-B-100 Agència de Gestió d'Ajuts Universitaris i de Recerca 2020/FI_B1-00641 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-1630 Agència de Gestió d'Ajuts Universitaris i de Recerca 2021/SGR-00186
Note:	Altres ajuts: acords transformatius de la UAB
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Ancient DNA (aDNA) ; Damage hotspot ; Mitochondrial DNA (mtDNA) ; Molecular damage profile ; Post-mortem DNA damage
Published in:	Molecular ecology resources, Vol. 25, Núm. 4 (May 2025) , art. e14061, ISSN 1755-0998

DOI: 10.1111/1755-0998.14061
PMID: 39776197

12 p, 1.1 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Experimental sciences > CREAF (Centre de Recerca Ecològica i d'Aplicacions Forestals)
Articles > Research articles
Articles > Published articles