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| Image: Unsplash |
A baby boy gets a fair share of about a little above fifty percent of mom's nuclear DNA and a baby girl receives almost equal percent from each of their parents. But in the case of mitochondrial DNA (mtDNA), the case is different. It was an established fact that a child derives that all the mitochondrial DNA from the mother until a team of researchers recently discovered it to be otherwise. The study team lead by Taosheng Huang, a pediatrician and medical geneticist who heads the Mitochondrial Diseases Program at the Cincinnati Children’s Hospital Medical Center uncovered those startling results on the first individual with mtDNA from both his parents.
In their study, the first proband identified happened to be a 4-y-old boy who was evaluated for fatigue, hypotonia, muscle pain, and ptosis at the MitoClinic at Cincinnati Children’s Hospital Medical Center (CCHMC). The child was previously suspected of carrying a mitochondrial disorder. Sequencing data of the family members revealed a higher degree of heteroplasmy in the family's DNA which resolved to about 40 per cent of mtDNA acquired from the paternal side/father. The results thus emerged to be a surprising and accidental demonstration of the current assumptions of mitochondrial inheritance.
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| The circular 16,569 bp human mitochondrial genome / Picture: Emmanuel Douzery |
Although hundreds of mtDNA are present in the female egg cell, not even a single of father's mtDNA is sustained until embryonation. A few of paternal mtDNAs present in the cytoplasm of sperm cell make upto the egg, where they at the end excluded prior to the formation of blastocyst. This sole dominance of maternal mtDNA in the embryos in every human cell is the usual natural inheritance mechanism.
The fate of the few mitochondrial DNA from the sperm cell is eliminated or lost either by self-destruction (Zhou et al. 2016) or by the action of autophagosomes during by the time of arrival into the embryos. This exclusion of mtDNA form father is probably regulated by a set of genes involved during the recombination process.
There are only two sets of large nuclear DNAs which combine during the recombination or mixing process, that produces a unique or mixed genetic combination in the offspring who derives the characteristics of both the parents. Mitochondrial DNAs, however, are large in number and possess variants or mutants within the same cell. One possible reason that nature chooses to conserve only a single set of mtDNA and from mother, and eliminate the other set could be to neutralize the state of combat that arises in the cell during the recombination process of numerous mitochondrial genome.
However, after the discovery of paternal share of mitochondrial DNA as discussed here, the list of encounters has increased and scientists seek answers to the mechanisms that are possible for the survival and passage of the fathers mtDNA into the embryo. Possibilities grow with either:
• the failure and/or loss of function mutation of genes responsible for the elimination of paternal mtDNA
• the paternal mitochondria developed mechanisms for their survival in the autophagosome degradation
These mechanisms, however, look insufficient in explaining the observational amount of paternal mtDNA inherited. The relative amount Paternal mitochondria as opposed to maternal is passed in a very low proportion (approx.. 0.1%). It implies that even if the inheritance occurred by defective eliminating genes, the amount of mtDNA should have been quite low.
• Accidental slippage of paternal mtDNA with multiple factors favouring its survival
It occurs likely that due to multiple factors caused the slippage of paternal mitochondria onto the fertilizing sperm and taking that transmission occurred with a high amount of mitochondria onto the zygote. Additionally, it is considered that the genes in question are defective, unable to eliminate the paternal DNA, there still stays a breach in understanding because multiple offspring as mentioned in the study by Dr Huang revealed high degrees of heteroplasmy.
.• The likelihood that the gene in question (eliminating genes) has some involvement in mtDNA replication or copy number control
The reason proposed by the researchers tries to associate the unknown locus of the nuclear genome to be associated with the elimination process. Also, the mitochondrial DNA must have replicated for being present in the observed amounts in the probands. Therefore, the gene in question influences the paternal mtDNA abundance by associating with some variants involved in the regulation of mitochondrial copy number control. All these processes here must somehow occur to carefully increase only the paternal mtDNA, leaving the maternal set untouched.
Reference:
Luo, S., Valencia, C. A., Zhang, J., Lee, N. C., Slone, J., Gui, B., ... & Chen, S. M. (2018). Biparental inheritance of mitochondrial DNA in humans. Proceedings of the National Academy of Sciences, 115(51), 13039-13044.
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