4. Molecular Evolution Flashcards Preview

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Flashcards in 4. Molecular Evolution Deck (20)
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1
Q

Requirement for a scientific theory

A
  • Must make testable predictions

- Must stand or fall according to whether the predictions are confirmed or refuted

2
Q

What is natural selection from today’s view point

A
  • Is not simply a hypothesis based on a finite set of data

- But a logical deduction from our knowledge of molecular genetics and ecology.

3
Q

What causes variation?

A
  • Mutation, due to changes in DNA sequence
  • Mostly mistakes during DNA synthesis (occasionally due to radiation)
  • Rare because DNA synthesis is exceedingly accurate - accurate due to the proof reading activity in DNA polymerase.
  • Most mutations are neutral or deleterious, a minority are beneficial
4
Q

What does ecology tell us about selection?

A
  • Individuals are in competition with predators, prey and members of their own species.
  • New alleles may increase or decrease reproductive success
5
Q

What is relative fitness?

A
  • Relative fitness (w) is the average number of surviving progeny of a genotype (compared with competing genotypes) after one generation.
  • If w<1, the frequency of the allele:
  • will decrease with each generation
  • until the allele disappears (negative selection)

• If w>1 the frequency of the allele
- will increase with each generation
- until the allele reaches fixation (positive selection)
~ (fixation is when all the other alleles have been displaced and this is the only allele.
• Sometimes you can end up with a balance where more than one allele are in balance in the population

6
Q

Give examples of some small and large mutations.

A

SMALL MUTATIONS:

  • Base substitutions
  • Small insertions
  • Small deletions

LARGE MUTATIONS:

  • Large DNA duplications
  • Large deletions
  • Insertions of transposable elements ~ RNA and DNA bits cut themselves and insert in another place
  • Viral insertions ~ especially retro viruses, insert into the genome and stably inherited
  • Chromosome rearrangements
7
Q

Number of mutations and molecular phylogeny

A

The mutations accumulate over time, so species that share a recent common ancestor will have fewer differences than species that are more distantly related.

  • RNA pol very highly conserved in evolution.
  • Sequence data can be used to generate evolutionary family trees.
8
Q

Main points of medical case study - HIV.

A
  • Suggested that HIV introduced to human population through a contaminated batch of polio vaccine. - early vaccines produced by growing polio virus on cultured monkey cells, which could’ve been contaminated by SIV (Simian immunodeficiency virus).
  • Phylogenetic tree was made and it showed that HIV is related to the SIV strands in west Africa – not the ones from east where the monkey cells were used.
9
Q

What are the patterns seen when comparing sequences for two species?

A
  • Consistently more differences (per unit length of DNA) in intron sequences than in exon sequences.
  • There are more differences looking at every third nucleotide, compared to the first two. ~ changes in the first 2 nucleotide, (unless it is neutral or advantageous), it will be removed by natural selection. Whereas, many of the changes in the 3rd nucleotide will not be removed by natural selection.
10
Q

Mutations that effect the reading frame.

A

Insertion or deletions - These mutations are almost always negative, and so will be removed by negative selection

11
Q

What are the different types of mutations?

A
  • Synonymous substitution - doesn’t change the AA

* Non-synonymous substitution - change in the AA

12
Q

Examples of high, moderate and low degree of conservation structures.

A

HIGHLY:
• Active sites of enzymes
• Structural regions of proteins

MODERATELY:
• Signal regions in 5’ and 3’UTRs
• Promoters

WEAKLY:
• Enhancers (in introns and intergenic DNA)
• Other intronic and intergenic DNA

13
Q

Gene duplication in evolution

A

• It is the major driving force for evolution.
• Once a gene has been duplicated:
- one copy can continue to maintain the original function
- while the other can evolve new functions.
- there are likely to be changes both in the coding sequence (i.e. in amino acid sequence) and in control sequences.

14
Q

Main points for the case study of the beta globin gene locus and mygoglobin and haemoglobin

A
  • Duplication of an ancestral Hb gene gave rise to myoglobin and haemoglobin
  • MYOGLOBIN:
  • In skeletal muscle
  • Monomeric protein
  • Hyperbolic O2 dissociation curve
  • Oxygen storage

• HAEMOGLOBIN:

  • RBCs
  • Tetrameric protein
  • SigmoidalO2 dissociation curve
  • Oxygen transport
15
Q

Main points for the case study of the globin gene and alpha and beta globin and gamma gene. And how does expression in these change in a lifetime?

A

• Ancestral globin gene has undergone multiple duplications and modifications to give the beta and alpha globin complexes on human chromosome 16.

  • The γ gene control sequences have evolved so that γ-genes are expressed during foetal life and the β-gene is expressed during postnatal life.
  • The above happened by promoter duplication along with coding sequence ~ promoter sequence has evolved so β and γ promoters now bind different transcription factors
  • They interact differently with gene enhancers
  • Differential control of beta and gamma genes
16
Q

Different Hb composition for the different types

A
  • Adult Hb (HbA) ~ alpha2beta2
  • Minor adult Hb ~ alpha2delta2
  • Fetal Hb (HbF) ~ alpha2gamma
  • Embryonic Hb (Hb Gower 2) ~ alpha2epsilon2
  • Embryonic Hb (Hb Gower 1) ~ zeta2epsilon2
17
Q

How has HbF evolved to have higher O2 affinity than HbA?

A

• Changes to the amino acid sequence of the gamma globin protein
• There are actually 2 γ genes (a gamma and b gamma)
- Coding for protine that differ by one AA residue
• Some adults still have HbF ~ doesn’t function too badly, only problems with their foetus as the baby may find it hard to take the oxygen.

18
Q

What is the pseudogene?

A
  • Ψβ
  • Non-functional gene - they cannot make a functional protein
  • They are made from a duplicated gene - but lose all the function
  • Clear sequence homology to the beta-globin gene
  • These are common in the genome
  • Most mutations are pseudogenes
19
Q

What is Fanconi’s anaemia?

A
  • Recessive lethal genetic disorder
  • Most affected patients die of bone marrow failure during childhood
  • Gene arises by random mutation
  • Eliminated by natural selection
  • Very low allele frequency
20
Q

Sickle cell anaemia (SCA)

A

• Point mutation in the β globin gene
• Single amino acid substitution ~ a hydrophilic a.a. (glutamic acid) is replaced by a hydrophobic a.a. (valine) at position 6
•Mutant Hb molecules
aggregate and form crystals when deoxygenated ~ Force red cells into characteristic “sickle” shape
• The crystals damage the red cell membrane resulting in: cell lysis causing anaemia, and cell adhesion
- causing blockage of small blood vessels, followed by tissue infarction
• Not eliminated by natural selection - some homozygous survive
• More common than Fanconi’s as heterozygous provides benefit that the people are less likely to die of both SCA and malaria (they can still catch malaria though).