TY - JOUR
T1 - Heteroplasmy concordance between mitochondrial DNA and RNA
AU - Zhang, Ruoyu
AU - Nakahira, Kiichi
AU - Choi, Augustine M.K.
AU - Gu, Zhenglong
N1 - Funding Information:
We thank Drs Kaixiong Ye, Xiaoxian Guo and Yudong Li for their discussions and comments on the manuscript. This work was supported by various funds from Cornell University, National Science Foundation (NSF) [MCB-1243588], and National Institute of Health (NIH) [R01 AI085286] to ZG, NIH [P01 HL108801], [R01 HL079904], [R01 HL112747] to AMKC and NIH/NCATS [KL2-TR-002385] to KN.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Mitochondrial DNA (mtDNA) heteroplasmies are associated with various diseases but the transmission of heteroplasmy from mtDNA to mitochondrial RNA (mtRNA) remains unclear. We compared heteroplasmies in mtRNA from 446 human B-lymphoblastoid cell lines to their corresponding mtDNA using deep sequencing data from two independent studies. We observed 2786 heteroplasmies presenting in both DNA and RNA at 1% frequency cutoff. Among them, the frequencies of 2427 (87.1%) heteroplasmies were highly consistent (less than 5% frequency difference) between DNA and RNA. To validate these frequency consistencies, we isolated DNA and RNA simultaneously from GM12282 cell line used in those two sequencing studies, and resequenced its heteroplasmy sites. Interestingly, we also observed the rapid changes of heteroplasmy frequencies during 4 weeks of the cell culture: the frequencies at Day 14 increased by >25% than those at Day 0. However, the heteroplasmy frequencies from the same time point were highly consistent. In summary, our analysis on public data together with in vitro study indicates that the heteroplasmies in DNA can be transcribed into RNA with high fidelity. Meanwhile, the observed rapid-changing heteroplasmy frequency can potentially disturb cell functions, which could be an overlooked confounding factor in cell line related studies.
AB - Mitochondrial DNA (mtDNA) heteroplasmies are associated with various diseases but the transmission of heteroplasmy from mtDNA to mitochondrial RNA (mtRNA) remains unclear. We compared heteroplasmies in mtRNA from 446 human B-lymphoblastoid cell lines to their corresponding mtDNA using deep sequencing data from two independent studies. We observed 2786 heteroplasmies presenting in both DNA and RNA at 1% frequency cutoff. Among them, the frequencies of 2427 (87.1%) heteroplasmies were highly consistent (less than 5% frequency difference) between DNA and RNA. To validate these frequency consistencies, we isolated DNA and RNA simultaneously from GM12282 cell line used in those two sequencing studies, and resequenced its heteroplasmy sites. Interestingly, we also observed the rapid changes of heteroplasmy frequencies during 4 weeks of the cell culture: the frequencies at Day 14 increased by >25% than those at Day 0. However, the heteroplasmy frequencies from the same time point were highly consistent. In summary, our analysis on public data together with in vitro study indicates that the heteroplasmies in DNA can be transcribed into RNA with high fidelity. Meanwhile, the observed rapid-changing heteroplasmy frequency can potentially disturb cell functions, which could be an overlooked confounding factor in cell line related studies.
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U2 - 10.1038/s41598-019-49279-7
DO - 10.1038/s41598-019-49279-7
M3 - Article
C2 - 31506522
AN - SCOPUS:85072045566
SN - 2045-2322
VL - 9
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 12942
ER -