UPSC Prelims 2021 Q66: Mitochondrial Replacement Therapy — Explained
In the context of hereditary diseases, consider the following statements:
1. Passing on mitochondrial diseases from parent to child can be prevented by mitochondrial replacement therapy either before or after in vitro fertilization of egg.
2. A child inherits mitochondrial diseases entirely from mother and not from father.
Which of the statements given above is/are correct?
- 1 only
- 2 only
- Both 1 and 2
- Neither 1 nor 2
Answer: (c) Both 1 and 2
Statement-wise explanation
- 1: correct — Mitochondrial replacement therapy (MRT) swaps the mother's faulty mitochondria for healthy ones from a donor egg, and it is done during in vitro fertilisation (IVF). In maternal spindle transfer, the mother's nuclear DNA is moved into an enucleated donor egg before fertilisation. In pronuclear transfer, the two pronuclei of the couple's zygote are moved into an enucleated donor zygote after fertilisation. The UK's Mitochondrial Donation Regulations (2015) allow both methods to prevent serious mitochondrial disease, so MRT can be done either before or after fertilisation.
- 2: correct — Mitochondrial DNA (mtDNA) passes only through the egg cytoplasm. Most of the sperm's mitochondria sit in its midpiece, and any that enter the egg are tagged and destroyed soon after fertilisation. So a mutation in mtDNA reaches the child only from the mother. That is why MRT acts on the mother's egg and never on the sperm.
How to eliminate
Statement 2 can be settled from basic biology: mitochondria come from the egg, so mitochondrial inheritance is maternal. The word 'entirely' looks like an absolute-word trap, but here it matches the textbook rule of strict maternal inheritance. Once Statement 2 is accepted, only two answers remain: Statement 2 alone, or both statements. Statement 1 then turns on one fact: MRT has a pre-fertilisation method (maternal spindle transfer) and a post-fertilisation method (pronuclear transfer). A candidate who remembers the 'three-parent baby' as an IVF technique has two clues. Statement 1 sits on the same mechanism (an egg or embryo with replaced mitochondria). And since IVF creates the embryo outside the body, it is plausible that the swap can happen at the egg stage or the zygote stage. If you are not sure of the timing, you have to know the fact. Remember: spindle transfer is before fertilisation, and pronuclear transfer is after.
Know more
Mitochondria are the cell's energy organelles. They carry their own small circular genome. Human mtDNA has 16,569 base pairs and 37 genes, mostly for parts of the energy (oxidative phosphorylation) chain. Mutations in mtDNA damage high-energy tissues such as the brain, muscle, heart and eyes. Leigh syndrome, MELAS and Leber's hereditary optic neuropathy are examples.
Why only the mother passes mtDNA: the egg carries thousands of mitochondria. The sperm's few mitochondria are destroyed after fertilisation. A cell can hold both mutant and normal mtDNA at once (heteroplasmy), so how severe the disease is depends on the share of mutant copies.
Mitochondrial replacement therapy (MRT), often called the 'three-parent baby' technique, gives the embryo the nuclear DNA of both parents and the mitochondria of a donor woman. Donor DNA is well under 1% of the child's total DNA.
| Technique | Stage | What is moved |
|---|---|---|
| Maternal spindle transfer | Before fertilisation | Mother's spindle–chromosome complex into an enucleated donor egg, which is then fertilised |
| Pronuclear transfer | After fertilisation | Parents' two pronuclei from the zygote into an enucleated donor zygote |
| Polar body transfer (experimental) | Before or after fertilisation | Polar body genome into a donor egg or zygote |
Milestones: In 2015 the UK became the first country to legally allow MRT, under the Human Fertilisation and Embryology (Mitochondrial Donation) Regulations. Each case needs approval from its regulator, the Human Fertilisation and Embryology Authority (HFEA). In 2016 the first reported MRT baby was born, using spindle transfer. Australia legalised MRT through Maeve's Law in 2022.
Limits for exam answers: Some mutant mtDNA can carry over into the embryo. Changes made this way are germline, so they pass to the next generation. Many 'mitochondrial disorders' are in fact caused by nuclear genes, which follow ordinary Mendelian inheritance and which MRT cannot prevent.
In the news
MRT was in the news in 2015–2021. The UK legalised it in 2015. The first 'three-parent baby' was reported in 2016. Australia's Maeve's Law Bill to allow mitochondrial donation was introduced in Parliament in 2021, the year of this exam.