The Severe Somatic Bottleneck in Mitochondrial DNA of Human Hair

Open Access
Barrett, Alison
Area of Honors:
Bachelor of Science
Document Type:
Thesis Supervisors:
  • Kateryna Dmytrivna Makova, Thesis Supervisor
  • Michael Axtell, Honors Advisor
  • Mitochondria
  • DNA
  • Heteroplasmy
  • Forensics
  • Hair
  • Bottleneck
  • Evolutionary Genetics
Heteroplasmy is the presence of a genetically heterogeneous population of mitochondrial DNA (mtDNA) within the same individual, tissue, cell or even the same mitochondrion. Heteroplasmy can result from de novo mutations or from inheritance of variants via the maternal lineage. In hair, a somatic bottleneck occurs during hair follicle development, which results in a restricted group of stem cells feeding the hair shaft with mitochondria. Here DNA was extracted from 5-10 hairs from each of 11 different humans, and mtDNA regions containing heteroplasmic sites previously identified in blood and cheek samples were amplified and sequenced using next-generation sequencing technology. We analyzed heteroplasmy allele frequency at such sites in individual hairs and estimated the somatic bottleneck in hair using population genetics modeling. The somatic bottleneck occurring during fetal development in hair was determined to be severe, i.e. equal to only 7.16 (95% confidence interval 3.4-23.6) mtDNA segregating units. This bottleneck is much more drastic than previously determined somatic bottlenecks for blood and buccal tissues (equal to 136 and 458 segregating units, respectively), as well as more drastic than, or comparable to, the germline bottleneck occurring during oogenesis (equal to 25-32 segregating units). Additionally, we found a positive correlation between donor’s age and variance in heteroplasmy allele frequency in hair, indicating that older individuals have accumulated more heteroplasmic variance in their hair. These findings have important implications for our understanding of mitochondrial DNA dynamics in the human body. Importantly, our results are also critical for forensics, as the heteroplasmic frequency from an individual’s hair sample may not be reflected in other hairs, blood or buccal samples from the same individual.