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.
| Original language | English (US) |
|---|---|
| Article number | 20190175 |
| Journal | Philosophical Transactions of the Royal Society B: Biological Sciences |
| Volume | 375 |
| Issue number | 1790 |
| DOIs | |
| State | Published - 2020 |
| Externally published | Yes |
Bibliographical note
Funding Information:Ethics. Hair samples were collected from mothers and their children with informed consent (under IRB 30432EP) in Central Pennsylvania. The samples were anonymized and de-identified prior to processing. Data accessibility. The sequencing reads are available at SRA under accession PRJNA534307. The code for population genetic analysis can be found in the electronic supplementary material, note S2 and at https://github.com/ammodramus/hair. Authors’ contributions. K.D.M., R.N., B.A. and A.B. conceived the project and devised the project study design. I.P. oversaw sample collection. A.B., B.A., K.D.M., A.Z., P.W. and R.N. were involved in the data analysis. A.B., B.A., K.D.M., A.Z. and P.W., contributed to the writing of the manuscript with comments from I.P. and R.N. Competing interests. We declare we have no competing interests Funding. This project was supported by a grant from NIH (R01GM116044). Additional funding was provided by the Office of Science Engagement, Eberly College of Sciences, The Huck Institute of Life Sciences and the Institute for CyberScience at Penn State, as well as, in part, under grants from the Pennsylvania Department of Health using Tobacco Settlement and CURE Funds. The department specifically disclaims any responsibility for any analyses, results or conclusions. Acknowledgements. We thank Jessica Beiler, MPH, for coordinating sample collection, clinical nurses from Penn State College of Medicine Pediatric Clinical Research Office and Lily Borhan for collecting the samples, and to volunteers for donating the samples for the study. Additionally, we thank Bonnie Higgins for her help. Mike Axtell provided helpful comments on the manuscript.
Publisher Copyright:
© 2019 The Author(s) Published by the Royal Society.
Keywords
- Forensics
- Hair development
- Heteroplasmy
- Mitochondrion
- MtDNA
- Somatic bottleneck