Lecture 32: Mitochondrial DNA Flashcards
(14 cards)
How large is the human mitochondrial genome?
16.5kbp
What is the consequence of there being many (thousands) of mitochondria in the liver cells?
Mitochondria are easy to purify, because there are so many of them.
Why is mitochondrial genetics different to Mendelian genetics?
During fertilisation, the egg provides half the nuclear DNA to the zygote and the sperm provides the other half of the nuclear DNA.
However, the sperm only provides its nucleus and little or no cytoplasm. This means all the cytoplasm comes from the egg, so all the mitochondria come from the mother.
This means mitochondrial genetics show maternal inheritance rather than the equal parental inheritance of the nuclear DNA.
How is meiosis different in the mitochondrial genome as opposed to the nuclear genome?
Mitochondrial genomes don’t recombine in meiosis as chromosomes do.
This means:
- Mutations which arise will be passed on to all descendants on the genetic background they arose
- Mutations cluster in mitochondrial genomes within particular lineages
How are mutations distributed throughout the mitochondrial genome?
Mutations are particularly prevalent in the D loop or control region which is “hypervariable”.
What is the consequence of all mitochondrial mutations being passed down to offspring?
The mt genome and the Y chromosome are one haplotype since there is no recombination. Individuals that share the same haplotype form a haplogroup.
(Remember: The concept of a haplotype - a shared set of mutations found in one block of DNA)
Describe the structure of the mitochondrial genome.
The mitochondrial genome is a circular chromosome 16.5kbp long, with the a hypervariable control region (aka D loop) which contains HV1 and HV2.
The mitochondrial genome codes mostly for oxidative phosphorylation, tRNA and rRNAs.
How is mitochondrial or Y chromosome DNA genotyped?
- Amplify mtDNA or Y chromosome DNA from buccal swabs using PCR
- Sequence whole mtDNA genomes or part of the genome, e.g. the 440bp HVR1 sequence
The primer pairs are labelled with different fluorescent labels and designed to amplify different sized products. This way many different PCR products can be run on the same capillary gel.
Does mitochondrial DNA or nuclear DNA accumulate mutations more quickly?
mtDNA mutations accumulate more quickly than nuclear DNA (~3 x 10-5 vs. 3 x 10-8).
HVR (in mtDNA) is one of the most variable sequences known (useful for forensics).
Is mitochondrial DNA in Africa the most or least varied?
The most varied.
Suggests that more mutations have accumulated there over a longer time, so H. sapiens mtDNA sequences originated in Africa.
What do phylogenetic trees show?
Evolutionary relationships between organisms or sequences traditionally drawn as phylogenetic trees.
- Nodes represent individual organisms or species
- Branch points represent common ancestors
- Distances along the branches represent time from the common ancestor
What do mitochondrial DNA haplogroups tell us about human migration out of Africa?
- The oldest mtDNA haplogroups are found in Africa (L1, L2 and L3).
- The pan-African haplogroup L3 radiated to form MACROHAPLOGROUPS M and N, which arose in North Eastern Africa.
- Individuals that had M and N mtDNA subsequently left Africa to colonize Europe and Asia 60,000–80,000 years ago.
- Haplogroups H, I, J, N1b, T, U, V, W and X are mainly derived from macrohaplogroup N and make up almost all of the mtDNA types found in Europe.
- In Asia, macrohaplogroups N and M radiated to generate mtDNA lineages A, B, C, D, F and G.
- Native Americans are known to have Asian ancestry because only five haplogroups (A, B, C, D and X) encompass all of the mtDNA variation in the New World, four of which came from Asia.
Give an example which shows how chloroplasts show the same maternal inheritance as mitochondrial DNA.
Leaf variegation in four o’clock plants:
The chloroplasts all come from the egg, as the pollen only has the nucleus and no cytoplasm.
This means the presence of green or white chloroplasts in the maternal plant determines what colour to F1 plant’s leaves are completely.
Explain why, in a small percentage of divisions, heteroplasmic cells give rise to homoplasmic cells, using an example.
Organelles in a heteroplasmic cell divide randomly into the progeny cells. In a small percentage of these random segregations, a daughter cell will receive all mutant or all normal mitochondria. This daughter cell is homoplasmic and all its daughter cells will be homoplasmic too.
An example: petite yeast cells
Heteroplasmic cells with normal and mutant mitochondria divide and on one division, all the mitochondria which randomly segregate into one of the daughter cells are mutants. This daughter cell is homoplasmic for the mutant mitochondria and so is a petite cell.
The petite mutants have large deletions in their mtDNA and are unable to carry out oxidative phosphorylation, so their growth is restricted.
