Molecular evolution

Question 1

Molecular evolution refers to changes to DNA. What does this arise from?

Answer 1

Mutation.

Question 2

What does purifying selection do?

Answer 2

Removes deleterious changes to DNA.

Question 3

What does positive selection do?

Answer 3

Fixes advantageous changes.

Question 4

What did a mutation in the Epas1 gene do?

Answer 4

Resulted in an allele in the Tibetan population that causes a high production of RBCs, an adaptation to altitude.

Question 5

Why did the mutant Epas1 gene not spread to the Han Chinese population?

Answer 5

At lower altitudes it proved disadvantageous as it causes a thickening of the blood.

Question 6

Define a non-synonymous mutation.

Answer 6

Base changes results in a change to the amino acid sequence that changes protein structure and thus gene function.

Question 7

Define a synonymous mutation.

Answer 7

Base change results in the same amino acid being produced due to the degenerate nature of the genetic code.

Question 8

How do silent (synonymous) mutations evolve?

Answer 8

Via genetic drift.

Question 9

Under genetic drift, the rate of fixation of silent (synonymous) mutations is proportional to what?

Answer 9

The rate of mutation itself.

Question 10

What does ‘n’ mean in terms of a population?

Answer 10

The number of reproductively active individuals that will contribute to the next generation.

Question 11

Define the molecular clock.

Answer 11

A model that predicts a steady rate of change over time, as mutation rate equals fixation rate.

Question 12

Define neutral theory.

Answer 12

Most mutations are essentially neutral, and there are little/no fitness consequences of DNA change.

Question 13

Give 3 pieces of support for neutral theory.

Answer 13

1. The rate of synonymous (silent) mutation is higher than the rate of non-synonymous mutation
2. Among non-synonymous mutations, changes that results in similar AAs being produced are more common
3. Non-coding sequences, e.g. pseudogenes and introns, evolve at a high rate similar to the molecular clock.

Question 14

Define the tick rate.

Answer 14

The speed at which the molecular clock moves.

Question 15

What causes the tick rate to vary?

Answer 15

The type of nucleotides involved.

Question 16

What does it mean if a gene is functionally constrained?

Answer 16

DNA changes have increased effects on protein structure and fitness.

Question 17

Why do functionally constrained genes have slower tick rates?

Answer 17

Because it is less likely a mutation will be neutral.

Question 18

The molecular clock can be used to infer speciation rates and divergence times. True or false?

Answer 18

True.

Question 19

Give the 3 assumptions of the molecular clock.

Answer 19

1. Genetic drift is constant
2. Mutation rate is constant
3. Selection is constant

Question 20

The molecular clock assumes genetic drift is constant. Why is this not always true?

Answer 20

Drift is stronger in small populations, so small/large populations vary.

Question 21

The molecular clock assumes mutation rate is constant. Why is this not always true?

Answer 21

Mutation is affected by metabolism: higher metabolism = more oxidative damage. Also species with faster generation times (more meiotic divisions) have higher tick rates.

Question 22

The molecular clock assumes selection is constant. Why is this not always true?

Answer 22

Adaptive bursts, e.g. in response to a new food source, and gene duplication alter the rate of selection.

Question 23

The molecular clock does not always give a linear mutation-fixation rate. What causes a curvilinear relationship?

Answer 23

Multiple substitutions over time. When all effectively neutral changes have been made, further changes will not increase divergence.

Question 24

In what codon position do most DNA changes occur?

Answer 24

The first codon position.

Question 25

If the DNA change is to the third codon position, the effect is likely to be?

Answer 25

Neutral

Question 26

Why does fossil evidence tend to cause an underestimate of divergence times? Give 2 reasons.

Answer 26

1. There is a lag between DNA change and a manifestation in the phenotype.
2. It takes a while for fossils to accumulate, i.e. the first fossil specimens of a species indicate when they began to die not when they were born

Question 27

Why is looking at molecular change a more accurate estimate of divergence times?

Answer 27

Because a change to DNA is the first thing to occur in speciation.

Question 28

What is Dn/Ds?

Answer 28

The relative rate of functional evolution.

Dn = non-synonymous coding mutation
Ds = synonymous non-coding mutation

Question 29

What does it mean if Dn/Ds

Answer 29

DNA changes are deleterious and removed by purifying selection.

Question 30

What does it mean if Dn/Ds > 1?

Answer 30

DNA changes are advantageous and fixed by positive selection.

Question 31

What can be said about the functional evolution rate if a pathogen changes host?

Answer 31

It is high.

Question 32

The functional evolution rate does not differentiate between what?

Answer 32

Relaxed or positive selection.

Question 33

What is Pn/Ps?

Answer 33

The polymorphism rate.

Question 34

Define the MacDonald-Kreitman (MK) test.

Answer 34

Seeks to identify genes that have arisen from adaptive evolution. This occurs when divergence between species exceeds polymorphism within, suggesting a gene has evolved more rapidly than the underlying mutation rate.

Essentially speciation is removing polymorphism within a population but fixing it between them, creating divergence.

Question 35

How does gene duplication occur at meiosis?

Answer 35

Can result from misaligned chromosomes at recombination, leading to unequal crossing over.

Question 36

Gene duplication is an extremely important mechanism in speciation. It is a common event. True or false?

Answer 36

False: it is v. rare.

Question 37

Duplicated genes have 3 different fates. What are they?

Answer 37

1. Neofunctionalisation: develop an entirely new function
2. Subfunctionalisation: duplicates each take on a singular function from the ancestral multifunctional gene
3. Pseudogenes arise from an accumulation of mis-sense mutations, resulting in gene death. The pseudogene is the residual nucleotide sequences left in the genome.

Question 38

What is dosage sensitivity?

Answer 38

Some genes are dosage sensitive in that they have an increased/descreased fitness effect based on copy number.