November 12, 2019
Mitochondria and Egg Cells: Why (mostly) uniparental inheritence?
- The Mitochondria in a cell is almost always, but not always, inherited from the mother to eliminate the cytoplasmic competition between two different cytoplasmic components (from different gametes).
- Mitochondrial DNA gets recombined, when needed, with the damaged genes getting replaced with copies from other chromosomes.
- Yeasts, Rats, and Bats can recombine mitchondrial DNA
- There's a recorded case of a human having heart cells containing mitochondria from the father.
- In a fertilized egg, the mitochondria from the male is either eliminated or selectively silenced, almost always.
- The zygote (the fertilized egg cell) contains 100,000 mitochondria 99.99% coming from the mother.
- The zygote divides a number of times within first two weeks to form the embryo: every time the zygote divides the 100,000 mitochondria are distributed among the new cells.
- Until mitochondria themselves start dividing (asexual reproduction), no new mitochondria are formed during this (first two weeks') period, and the new embryo cells must utilise whatever mitochondria are available to them for their development: any embryo cells that cannot do this die.
- If the embryo is a female embryo, the egg cells start forming after two/three weeks, and contain around 10 mitochondria, each containing just a single copy of the chromosomes: there's variation in the mitochondrial sequences within these oocytes, and more than 50% contain errors in the DNA sequence.
- The mitochondrial DNA is verified for a match against the nuclear DNA
- The number of egg cells formed in a female embryo is around 100 after the first three weeks --> seven million after five months --> two million after birth --> 300,000 by menstruation --> 25,000 by age 40: only 200 of which ovulate during female's reproductive life.
Mitochondria and Ageing: Anti-oxidants do not increase lifespan
- Denham Harman proposed relation between free-radicals and ageing in 1972: theorized that higher metabolism rate leads to higher free-radicals which cause higher cell damage leading to cell death and, consequently, ageing.
- Richard Cutler, in 1980's, showed -- erroneously -- that long-lived animals have a higher levels on anti-oxidants in their cells, and conversely, short-lived animals have lower anti-oxidant levels: the data was flawed since he divided the number of anti-oxidants by the metabolic rate in the respective organism, which has the following problems:
- Opposite is true: a short-lived rat with higher metabolic rate (7 times human metabolic rate) also has a higher anti-oxidant concentration.
- Several independent studies have confirmed a negative correlation between the antioxidant level and lifespan i.e. the lifespan decreases with the increase in antioxidants: a correlation not causation, since the lifespan is independent of antioxidant concentration.
- The levels of antioxidant is maintained wrt the metabolic rate: low-for-low/high-for-high to maintain a flexible redox state within the cell.