Abstract
Heteroplasmy is the presence of variable mitochondrial DNA (mtDNA) within the same individual. The dynamics of heteroplasmy allele frequency among tissues of the human body is not well understood. Here, we measured allele frequency at heteroplasmic sites in two to eight hairs from each of 11 humans using next-generation sequencing. We observed a high variance in heteroplasmic allele frequency among separate hairs from the same individual—much higher than that for blood and cheek tissues. Our population genetic modelling estimated the somatic bottleneck during embryonic follicle development of separate hairs to be only 11.06 (95% confidence interval 0.6–34.0) mtDNA segregating units. This bottleneck is much more drastic than somatic bottlenecks for blood and cheek tissues (136 and 458 units, respectively), as well as more drastic than, or comparable to, the germline bottleneck (equal to 25–32 or 7–10 units, depending on the study). We demonstrated that hair undergoes additional genetic drift before and after the divergence of mtDNA lineages of individual hair follicles. Additionally, we showed a positive correlation between donor's age and variance in heteroplasmy allele frequency in hair. These findings have important implications for forensics and for our understanding of mtDNA dynamics in the human body.This article is part of the theme issue ‘Linking the mitochondrial genotype to phenotype: a complex endeavour’.
Highlights
Mitochondria play an essential role in cellular energy metabolism via coding for important genes involved in bioenergetics [1,2]
MtDNA is a circular molecule composed of 16 569 base pairs and containing 37 genes [1]. mitochondrial DNA (mtDNA) has an elevated mutation rate compared to nuclear DNA probably because of an increased number of replications per cell division, a less efficient DNA repair system and/or exposure to oxygen radicals generated as a by-product of oxidative phosphorylation [3]
Each cell has hundreds to thousands of mtDNA copies that replicate continuously in both proliferating and differentiated cells, which might lead to a rapid accumulation of somatic mutations [4]. mtDNA mutations may result in mitochondrial diseases [1,5] and have been linked to ageing [6]
Summary
Mitochondria play an essential role in cellular energy metabolism via coding for important genes involved in bioenergetics [1,2]. Heteroplasmy at a site can vary in allele frequencies between cells, tissues or organs of an individual [1]. Random genetic drift can change heteroplasmy allele frequencies within the lifetime of an individual. Each root of the hair is formed from a small group of stem cells in the hair follicle [16] This leads to a limited pool of mtDNA molecules, i.e. somatic bottleneck [15]. We explored the somatic bottleneck and changes in heteroplasmy allele frequencies occurring in human hair. We determined the size of somatic mtDNA bottleneck in hair and analysed the changes in heteroplasmy allele frequency as related to human ageing. Our results contribute to our understanding of mtDNA variation in the human body and have implications for forensics
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