Molecular Evolution Flashcards

1
Q

Define Evolution

A

Change inheritable characteristics of biological populations over successive generations.

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2
Q

Natural Selection

A

The effects of a wide range of factors on the frequency of heritable changes in a species.

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3
Q

Fitness

A

How well a species is able to reproduce in its environment

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4
Q

What is selected for in terms of fitness?

A

Anything that increases fitness is selected for, anything that decreases fitness is selected against.

Other neutral changes will vary randomly.

If the environment is changed, fitness can change.

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5
Q

What is the modern synthesis?

A

The idea that evolution can be unified with genetics to explain molecular processes underlying evolution. Genetic variation is the main source of heritable changes in a species.

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6
Q

What affects frequencies of genetic variants?

A

Selection:
- Genetic variants that confer a positive advantage will be selected for and vica versa.

Mutation:

  • Variation in the genome aries.
  • Large numbers of genomic variants are already in the population and their frequency depends on selection and when they first arose.
  • A rare variant (SNV) may have arisen very recently or be deleterious and being selected against or both.

Migration:
- The physical movement of people from a different population results in new pools of variants being introduced to an existing population. This is called genetic admixture. Population frequencies of specific variants can change purely due to admixture and not be disease related.

Genetic drift:
- This is how the frequency of a variant changes in a population due to change. Not all organisms in a population will pass on their genetic variants. Random change in variant allele frequency. Mechanisms such as recombination will also result in not all variants being passed on.

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7
Q

What is sequence conservation?

A

The conservation of a DNA sequence that is vital to the survival of an organism so does not normally show much evidence of variation.

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8
Q

What happens to variants in the sequence conservation region?

A

Most variants in these regions will be selected against as they are likely to have a strongly deleterious effect. There is some flexibility for variation in the third base of codons as the genetic code is degenerate.

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9
Q

Describe sequence conservation in genes

A

High conservation - coding regions (not exons - as these contain non-coding regions)

Intermediate conservation - promoter, 5’UTR, 3’UTR, terminator

Low conservation - introns, 3rd base of condons and terminator

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10
Q

What is cross-species comparison used for?

A

It can be used to generate an evolutionary profile for a gene or gene family.

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11
Q

Give an example of conservation

A

NAMPT - nicotinamide phosphoribosyltransferase is conserved with other species

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12
Q

What is phylogenetics?

A

The study of evolutionary relationships between species

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13
Q

What are phylogenetic trees useful for?

A

The main aim is to illustrate the relatedness of different species/strains/sequences. The distance between two entities on a tree is usually related to how similar they are. The distance is normally related to both evolutionary pressures and to time.

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14
Q

What do strong evolutionary pressures result in?

A

Strong evolutionary pressures can result in changes in organisms even if there is not a great distance between them.

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15
Q

How did they show that Polio Vaccine did not cause HIV?

A
  • It was theorised that contaiminated polio vaccine introduced SIV into humans in DRC, Africa.
  • Some polio vaccines used to be produced using cultured chimpanzee cells, which could have been infected with SIV (which is closely related to HIV).
  • However Worobey et al (2004) investigated this using phylogenetics. The tree demonstrates that the SIV genome in DRC wild chimpanzees was completely distinct from all HIV genomes.
  • Other SIV strains were likely to be the source as they are closely related to HIV.
  • Showed that the polio vaccine was not contaminated with anything that caused HIV.
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16
Q

What is gene duplication?

A

This is duplication of a DNA sequence a gene.

17
Q

How does gene duplication occur?

A

The typical mechanism is unequal crossing over during meiosis.

18
Q

What happens after the duplication of a gene?

A

After duplication:

  • One copy can continue the original function.
  • The other copy can evolve new function(s) by changes in the coding sequence and/or control sequences.
19
Q

What is unequal crossing over?

A

It is when recombination between sequences that are not the correct sequence but are very similar.

20
Q

What does unequal crossing over lead to?

A

Low copy number repeat sequences

see diagram

21
Q

What are the globin genes arranged into?

A

Two clusters

22
Q

What are the two clusters of the globin gene, where are they located and how many genes do they contain?

A

Alpha-like on chromosome 16 - 4 genes and 3 pseudogenes

Beta-like on chromosome 11 - 5 genes and 1 pseudogene

23
Q

How are the globin genes arranged?

A

They are arranged in order of expression during development

24
Q

What is Beta LCR?

A

It is a locus control region that regulates the expression of genes.

25
Q

Describe the evolution of the globin gene clusters

A
  • The phylogenetic tree suggests that there was single ancestral myoglobin like molecule. This duplication lead to myoglobin.
  • It is clear that globin genes have evolved through duplication and accumulation of mutations (divergence).
  • Some are functioning genes and some are not (pseudogenes).
  • The divergence of promoters has occurred, so they bind different transcription factors and allow expression of genes at different stages of development.
26
Q

What are pseudogenes?

A

After gene duplication, one gene can maintain the original function and the other can diverge.
Pseudogenes typically have many mutations and are non-functional. There are many of them in the genome and they complicate PCR/sequencing etc

27
Q

When does sickle cell disease symptoms typically start and why?

A

Around 5-6 months of age, this is because of the conversion of HbF to HbA.

28
Q

What are the main symptoms of SCD?

A
  • Anaemia: fatigue, restlessness, jaundice
  • Acute pain episodes- “crises” - due to oxygen deprivation of tissues
  • Increased frequency of infections - spleen damage
  • Also stroke, pulmonary hypertension, gallstones, liver and kidney problems, joint problems, delayed puberty
29
Q

Describe of genetics of SCD

A

Single base change in the beta-globin gene of Haemoglobin A. This is known as Haemoglobin S (HbS). Codon change is a GAG to GTG. This is Glu-> Val at position 7 of the protein. It is an autosomal recessive disease

30
Q

What are the effects of having one/two copies of the HbS variant?

A

Having two copies of the HbS variant has significant negative effects on reproductive ability - SCD.
However, one copy of the HbS variant confers resistance to severe malaria. This “heterozygote advantage” means that the HbS variant is maintained in the population when otherwise it would have been selected against and lost. The original mutation occurred about 7300 years ago.