Pronounced somatic bottleneck in mitochondrial DNA of human hair
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Pronounced somatic bottleneck in mitochondrial DNA of human hair. / Barrett, Alison; Arbeithuber, Barbara; Zaidi, Arslan; Wilton, Peter; Paul, Ian M.; Nielsen, Rasmus; Makova, Kateryna D.
In: Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 375, No. 1790, 20190175, 2020.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Pronounced somatic bottleneck in mitochondrial DNA of human hair
AU - Barrett, Alison
AU - Arbeithuber, Barbara
AU - Zaidi, Arslan
AU - Wilton, Peter
AU - Paul, Ian M.
AU - Nielsen, Rasmus
AU - Makova, Kateryna D.
N1 - Publisher Copyright: © 2019 The Author(s) Published by the Royal Society.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - Forensics
KW - Hair development
KW - Heteroplasmy
KW - Mitochondrion
KW - MtDNA
KW - Somatic bottleneck
U2 - 10.1098/rstb.2019.0175
DO - 10.1098/rstb.2019.0175
M3 - Journal article
C2 - 31787049
AN - SCOPUS:85075941985
VL - 375
JO - Philosophical Transactions of the Royal Society B: Biological Sciences
JF - Philosophical Transactions of the Royal Society B: Biological Sciences
SN - 0962-8436
IS - 1790
M1 - 20190175
ER -
ID: 336608698