Cuesta-Aguirre Daniel R, Amor-Jimenez Cristina, Malgosa Assumpció, Santos Cristina
Research Group in Biological Anthropology, Biological Anthropology Unit, Department of Animal Biology, Vegetal Biology and Ecology, Universitat Autònoma de Barcelona, Barcelona, Spain.
Centre de Recerca Ecològica i d'Aplicacions Forestals, Universitat Autònoma de Barcelona, Barcelona, Spain.
Mol Ecol Resour. 2025 May;25(4):e14061. doi: 10.1111/1755-0998.14061. Epub 2025 Jan 7.
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.
线粒体DNA（mtDNA）分析对于理解人类群体结构和遗传多样性至关重要。然而，死后DNA损伤带来了挑战，使得分析变得困难。DNA保存受环境条件影响，这在其他因素中，使古代mtDNA混合图谱中内源性变异与人为产物的区分变得复杂。本研究旨在为古代mtDNA开发一种分子损伤图谱，可成为分析古代遗骸中mtDNA的有用工具。从ENA数据库中汇编了一个包含427个全基因组或代表不同历史时期和气候区域个体的mtDNA序列捕获数据集。还纳入了现代和经尿嘧啶DNA糖基化酶（UDG）处理的古代样本，并用于确定受损读数的水平。结果表明，来自寒冷地区的样本受损读数百分比最低，其次是干旱、寒冷、热带和温带地区，寒冷和温带地区之间存在显著差异。生成了一个全球损伤图谱，识别出2933个位置（占所考虑位置的25%），在超过23.8%的分析样本中存在损伤，被视为损伤热点。值得注意的是，这些热点中有2856个从未被报告为损伤或突变热点，或异质性位置。与编码区相比，非编码区按位置的损伤热点频率略高。总之，本研究为古代mtDNA分析提供了一种分子损伤图谱，有望成为解释古代样本中mtDNA变异的有价值工具。
