Allele frequency selection and no age-related increase in human oocyte mitochondrial mutations
Aug 6, 2025·
B Arbeithuber, K Anthony, B Higgins, P Oppelt, O Shebl, I Tiemann-Boege, F Chiaromonte, T Ebner, KD Makova
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0 min read
Abstract
Mitochondria, cellular powerhouses, harbor DNA [mitochondrial DNA (mtDNA)] inherited from the mothers. mtDNA mutations can cause diseases, yet whether they increase with age in human oocytes remains understudied. Here, using highly accurate duplex sequencing, we detected de novo mutations in single oocytes, blood, and saliva in women 20 to 42 years of age. We found that, with age, mutations increased in blood and saliva but not in oocytes. In oocytes, mutations with high allele frequencies were less prevalent in coding than noncoding regions, whereas mutations with low allele frequencies were more uniformly distributed along the mtDNA, suggesting frequency-dependent purifying selection. Thus, mtDNA in human oocytes is protected against accumulation of mutations with aging and having functional consequences. These findings are particularly timely as humans tend to reproduce later in life.
Type
Publication
Science Advances
Authors
Postdoctoral scholar
In Prof. Makova’s lab Barbara was interested in the accurate measurement of rare mutations. Her project was focused on the inheritance of mitochondrial DNA; particularly, analysis of de novo mutations in the germ line, as well as the inheritance of low-level variants.
Authors
Francesca is a statistician developing methods for the analysis of large, high-dimensional and complex data, and applying such methods in contemporary “Omics” sciences and other scientific fields – including Meteorology and Economics.
Authors
Professor
Kateryna is interested in genomics, evolution, and human genetics.
Her lab studies mutations using both computational and experimental
approaches. Additional topics of interest include sex chromosome
evolution and genomics of childhood obesity.