Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Genomics > The Mitochondrial Genome > Flashcards

The Mitochondrial Genome Flashcards

1
Q

What are some of the lesser known functions of the mitochondria?

A
  • Haem synthesis
  • Neurotransmitter synthesis, e.g. glutamate
  • Nucleotide synthesis - Produces purine intermediates which are required for DNA synthesis
  • Produces reactive Oxygen species (via oxidative phosphorylation) - reactive oxygen species are important for cell signalling
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Why is it that mitochondria are said to be important in innate immunity?

A
  • Nn the surface of mitochondria there’s the mitochondrial antiviral-signalling complex which is important for producing inflammation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are some of the features of the mitochondrial genome?

A
  • Mitochondrial DNA (mtDNA) is a double stranded circular molecule
  • mtDNA is really small
  • Consists of a heavy and a light strand
  • Multicopy genome (10-100,000 copies per cell) - in contrast to the human genome which only has 2 copies per cell (diploid genome)
  • Contains 37 genes
  • Maternally inherited
  • Doesn’t contain introns
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the difference between the heavy and light strands that mean they are given those names?

A
  • Heavy strand contains a large amount of guanine nucleotides while light strand contains a large amount of cytosine.
  • Guanine is a purine base which is a double ring instead of a single ring like cytosine which means guanine is heavier than cytosine
  • Fact that heavy strand contains more guanine means it’s more dense than light strand which is why it’s called the heavy strand.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What do the 37 genes within the mitochondrial genome encode for?

A
  • 13 encode for oxidative phosphorylation protein subunits
  • 22 encode for transfer RNAs (tRNAs)
  • 2 encode for ribosomal RNAs (rRNAs)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Mitochondrial DNA contains a non-coding region what structures are present within this non-coding region?

A
  • Heavy and light strand promoters
  • Origin of the heavy strand
  • 7S DNA
  • D-loop
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the D-loop (displacement loop)?

A
  • Replicated segment of the heavy strand that’s hydrogen bonded to the light strand
  • It forms when replication of heavy strand is arrested/stopped temporarily
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

In which part of the non-coding region of the mitochondrial genome does mtDNA replication start?

A

starts in Origin of heavy strand (OH)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

In which part of the non-coding region of the mitochondrial genome does transcription start?

A

Transcription starts at Heavy strand promoter (HSP) and Light strand promoter (LSP)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How is mitochondrial DNA packaged so that it can fit inside the mitochondria?

A
  • mtDNA is packaged into structures called nucleoids
  • There are one or two copies of mtDNA per nucleoid
  • Transcription factor A (TFAM) acts as a histone protein - mtDNA wraps around the TFAM to form the nucleoid structure
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Some triplet codons code for different amino acids in mitochondrial DNA compared to nuclear DNA, give some examples where this is the case.

A
  • AUA codes for methionine - AUA codes for isoleucine in nuclear DNA
  • UGA codes for tryptophan - Codes for stop codon in nuclear DNA
  • AGA and AGG are stop codons - Code for arginine in nuclear DNA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is a mitochondrial haplogroup?

A
  • A haplogroup created by differences in mitochondrial DNA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What characteristics of mitochondrial DNA mean that mitochondrial DNA haplogroups developed over time?

A
  • mtDNA is maternally inherited which means that all the different mitochondrial genes are inherited from one parent in groups
  • mtDNA doesn’t recombine which means that as mutations within the mtDNA acquired over time, the mutations weren’t able to be repaired and were maintained within the population
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the first 4 mitochondrial DNA haplogroups and when did they develop?

A
  • L0-L3 haplogroups developed in sub-Saharan Africa 130,000 - 200,000 years ago
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What other haplogroups developed from the L3 haplogroup?

A
  • Haplogroups M and N then arose from L3 around 65,000 – 70,000 years ago
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Mitochondrial DNA produces 13 proteins used in oxidative phosphorylation, what role do these proteins have in the process of oxidative phosphorylation?

A
  • Oxidative phosphorylation requires five enzyme complexes
  • mtDNA encodes for some of the subunits that make up every complex involved in oxidative phosphorylation apart from complex II.
17
Q

There are over 100 different proteins involved in oxidative phosphorylation but only 13 of those are encoded for by genes in the mtDNA in the mitochondria. Where are the rest of the genes that encode for these proteins and what does it mean for the proteins that they aren’t produced in the mitochondria?

A
  • The rest of the proteins involved are encoded for by genes within nuclear DNA
  • This means that when these proteins are produced they have to migrate from the cytoplasm to the mitochondria.
18
Q

To make the 13 mitochondrial proteins involved in oxidative phosphorylation mtDNA genes must be replicated, transcribed and translated. The proteins required for these processes aren’t produced in the mitochondria. Where are they produced and what does it mean for these proteins?

A
  • The genes that encode for these proteins are found within nuclear DNA
  • This means that just like the majority of proteins involved in Oxidative phosphorylation, these nuclear proteins have to migrate to the mitochondria from the cytoplasm.
19
Q

What are the main enzymes involved in mitochondrial DNA replication?

A
  • Mitochondrial DNA polymerase (Polγ)
  • Twinkle helicase - mtDNA helicase, unwinds DNA for replication
  • Single stranded binding protein 1 (SSBP1)
  • Transcription factor A (TFAM) - packages and protects mtDNA
20
Q

What are some properties of the mitochondrial DNA polymerase?

A
  • Heterotrimer protein - consists of 3 different subunits
  • One catalytic subunit (POLγA)
  • Two accessory subunits (POLγB)
21
Q

What role do the POLγA and POLγB subunits play in the activity of mitochondrial DNA polymerase?

A
  • POLγA contains a 3’ – 5’ exonuclease domain to proofread newly synthesized DNA
  • POLγB enhances interactions with DNA template and increases activity and processivity of POLγA.
22
Q

What is the processivity of an enzyme?

A

An enzyme’s ability to catalyze consecutive reactions without releasing its substrate

23
Q

What is the function of the mitochondrial DNA helicase (TWINKLE) in mtDNA replication?

A
  • Unwinds double stranded mtDNA template to allow replication by the mitochondrial DNA polymerase
24
Q

What is the function of the mitochondrial single stranded binding protein (mtSSBP)?

A

Binds to single stranded mtDNA formed once the duplex has been unwound and has a number of different functions including:

  • Protecting single stranded mtDNA against nucleases
  • Preventing secondary structures forming from single stranded mtDNA
  • Enhancing mtDNA synthesis by interacting with TWINKLE helicase and stimulating its activity
25
Q

Explain the steps involved in replication of the heavy strand of mtDNA

A
  1. Parental heavy strand is displaced and is then coated with mtSSBP.
  2. TWINKLE helicase then unwinds the mtDNA of the parental heavy strand
  3. Mitochondrial RNA Polymerase (POLRMT) synthesizes RNA primer using light strand as template
  4. POLγ then takes over from POLRMT and then uses RNA primer to replicate mtDNA at OH (origin of replication for heavy strand)
26
Q

During replication of the heavy strand why does mitochondrial single stranded binding protein bind to displaced parental heavy strand?

A
  • Prevents the mitochondrial RNA polymerase from initiating RNA synthesis on that displaced strand - makes sure that RNA primer produced forms first part of newly synthesised heavy strand
27
Q

Explain the steps involved in replication of the light strand of mtDNA

A
  1. As the mtDNA replication machinery goes around synthesising the new heavy strand it eventually passes OL (Light strand origin of replication).
  2. When this occurs the parental heavy strand folds at the OL to form a Stem loop structure.
  3. This stem loop structure prevents mtSSBP from binding which leaves a small section of the parental heavy strand available which is used by Mitochondrial RNA polymerase as a template to synthesise an RNA primer.
  4. POLγ uses RNA primer to replicate light strand DNA at OL in the opposite direction to heavy strand replication.
28
Q

What process needs to occur once the 2 newly synthesised heavy and light strands are formed?

A
  • The newly synthesised mitochondrial DNA molecule needs to be seperated from the parental mitochondrial DNA molecule
29
Q

What enzyme catalyzes the seperation of the 2 mitochondrial DNA molecules once replication has occured?

A

Topoisomerase 3𝛼

30
Q

What are some charecteristics of mitochondrial diseases?

A
  • Rare monogenic diseases
  • Usually affect highly metabolic organs
  • Wide disease spectrum e.g. Range from Hearing loss to Fatal cardiomyopathy in infancy
  • Can Start at any age
  • Genetically heterogeneous - Mitochondrial diseases occur due to mutations in Mitochondrial or nuclear genes
  • Almost all are incurable
31
Q

Why do mitochondrial disease usually affect highly metabolic organs?

A

Because these organs contain high amounts of mitochondria

32
Q

Give some examples of mitochondrial diseases

A
  • Leigh syndrome - Most common mitochondrial disease presentation
  • KSS - Kearns-Sayre Syndrome
33
Q

What are the different types of inheritance patterns for mutations that cause mitochondrial diseases?

A
  • Because mtDNA is maternally inherited it means mutations in the mitochondrial DNA that cause mitochondrial disease only show maternal inheritance.
  • However, there are also mutations in nuclear DNA that can cause mitochondrial disease and these mutations show a variety of inheritance patterns including:
    • Autosomal dominant/recessive
    • X-linked
34
Q

What is heteroplasmy?

A

State in which a cell contains more than one type of mitochondrial variant

35
Q

What does the fact that most mtDNA is herteroplasmic mean for the manifestation of a mitochondrial disease?

A
  • It means that for a particular variant within mtDNA to cause a diease it has to be prevalent at a very high level within the mitochondria.
  • Around 80% of all variants within the mtDNA of a mitochondria have to be that type of the disease phenotype to show

Genomics (18 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions