J Islamabad Med Dental Coll 2020 153 

Ope n Acce ss  

 Mitochondrial DNA Inheritance Mystery  
 

Irfan Afzal Mughal 

Associate Professor, Department of Physiology, HBS Medical College, Islamabad, Pakistan  

 

 

Mitochondrial DNA (mtDNA) was discovered in 

1963. Its inheritance was labeled as maternal type. 

Some selective mechanisms are still mysterious, that 

how paternal mtDNA is selectively destroyed. 

Marking of ubiquitin to sperm mitochondria 

facilitates the deselection of paternal mitochondrial 

DNA molecules. After fertilization (four to eight-cell 

stage) paternal mtDNA is not detected usually. 

Recently the concept of mixed mtDNA haplotype 

was found, which suggests biparental mtDNA 

inheritance.1 

Previously it was hypothesized that paternal mtDNA 

molecules were diluted in the fertilized egg. Later, in 

unicellular alga Chlamydomonas and Medaka fish, 

mtDNA was found to be eliminated after 

fertilization.2 This theory remained under discussion 

for decades. Researchers described the role of 

mitophagy in the selective elimination of paternal 

mitochondria.3 

Principally, the paternal inheritance from sperm 

mitochondria to egg at fertilization is 1,000-fold less 

than the mitochondrial number in the oocyte. There 

is always an inevitable sexual conflict in the 

competition between paternal and maternal 

mitochondrial inheritance, which suggests that 

paternal leakage and presence of heteroplasmy is 

due to this sexual conflict. In healthy people, 

heteroplasmy i.e. presence of more than one 

mtDNA type, is common and this can increase with 

the advancing age, as there are more chances of 

mutations.4 

In a recent study paternal inheritance of mtDNA is 

revitalized in healthy people. In three independent 

families and moreover, several generations of these 

families, it was confirmed by DNA sequencing which 

was performed in two different laboratories. Luo et 

al sequenced mtDNA of several members of a family 

where many individuals were found to carry a high 

level of mtDNA heteroplasmy and suggested that 

inheritance of mtDNA was from both parents due to 

genetic trait.5 

The inheritance pattern as explained by Luo et al 

suggested that elimination of paternal mitochondria 

was due to a gene on one of the autosomes. 5 This 

observation may be used to identify signal pathways 

which are responsible for paternal inheritance of 

mtDNA.6 

An autologous gene signature was seen in 7 out of 

11,035 trios. The allelic fraction was 5-25% and 

biparental inheritance was seen in 0.06% of 

offspring. On whole-genome sequencing, it was 

found that unique nuclear mtDNA segments 

(“mega-NUMTs”) were transmitted by father in all 

these 7 families. These were 0.13% in fathers and 

this was an autosomal transmission of haplotype. It 

was concluded that rare paternal mtDNA 

heteroplasmy can be due to rare cryptic mega-

NUMTs (a large and rare mtDNA segment).7 

E D I TOR I A L 

Correspondence:  
Irfan Afzal Mughal 
Email: the.mughal@hotmail.com 

Cite this editorial: Mughal IA. Mitochondrial DNA 

Inheritance Mystery. J Islamabad Med Dental Coll. 2020; 
9(3): 153-154 
Doi: 10.35787/jimdc.v9i3.606 



 

             J Islamabad Med Dental Coll 2020 154 

These 11,035 were unrelated mother-father-

offspring trios. In 10,764 trios, the father harbored 

at least one variant (Allelic fraction >5%) which was 

not detected in the mother. It was observed that 

seven fathers-off springs pairs were carrying NUMT 

with two breakpoints on the mtDNA sequence, 500 

bp away from each other. The same mega rare 

NUMT was observed in one mother in a different 

family and subsequently her child also carried it. 

Both of them were carrying the same haplotype 

allelic fraction.7 As these families were unrelated, 

the inheritance of rare NUMT in mixed haplotype 

adds more weightage to the argument of paternal 

inheritance. 

R e f e r e n c e s  

1. Vissing J. Paternal comeback in mitochondrial DNA  

inheritance. PNAS. 2019; 16(5): 1475 -6. Doi: 

10.1073/pnas.1821192116 

2. DeLuca SZ, O'Farrell PH. Barriers to male transmissio n  

of mitochondrial DNA in sperm development. Dev 

Cell. 2012; 22(3): 660-8. Doi: 10.1016/j.devcel.2011. 

12.021 

3. McWilliams TG, Prescott AR, Montava-Garriga L, Ball  

G, Singh F, Barini E, et al. Basal mitophagy occurs 

independently of PINK1 in mouse tissues of high  

metabolic demand. Cell Metab. 2018; 27(2): 439 -49. 

e5. Doi: 10.1016/j.cmet.2017.12.008 

4. Radzvilavicius AL, Lane N, Pomiankowski A. Sexual 

conflict explains the extraordinary diversity of 

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0437-8 

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946115 

6. Rius R, Cowley MJ, Riley L, Puttick C, Thorburn DR, 

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7. Wei W, Pagnamenta AT, Gleadall N, Sanchis-Juan A, 

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C, Turro E, Caulfield MJ. Nuclear-mitochondrial DNA  

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