Molecular evolution Flashcards
Molecular evolution refers to changes to DNA. What does this arise from?
Mutation.
What does purifying selection do?
Removes deleterious changes to DNA.
What does positive selection do?
Fixes advantageous changes.
What did a mutation in the Epas1 gene do?
Resulted in an allele in the Tibetan population that causes a high production of RBCs, an adaptation to altitude.
Why did the mutant Epas1 gene not spread to the Han Chinese population?
At lower altitudes it proved disadvantageous as it causes a thickening of the blood.
Define a non-synonymous mutation.
Base changes results in a change to the amino acid sequence that changes protein structure and thus gene function.
Define a synonymous mutation.
Base change results in the same amino acid being produced due to the degenerate nature of the genetic code.
How do silent (synonymous) mutations evolve?
Via genetic drift.
Under genetic drift, the rate of fixation of silent (synonymous) mutations is proportional to what?
The rate of mutation itself.
What does ‘n’ mean in terms of a population?
The number of reproductively active individuals that will contribute to the next generation.
Define the molecular clock.
A model that predicts a steady rate of change over time, as mutation rate equals fixation rate.
Define neutral theory.
Most mutations are essentially neutral, and there are little/no fitness consequences of DNA change.
Give 3 pieces of support for neutral theory.
- The rate of synonymous (silent) mutation is higher than the rate of non-synonymous mutation
- Among non-synonymous mutations, changes that results in similar AAs being produced are more common
- Non-coding sequences, e.g. pseudogenes and introns, evolve at a high rate similar to the molecular clock.
Define the tick rate.
The speed at which the molecular clock moves.
What causes the tick rate to vary?
The type of nucleotides involved.
What does it mean if a gene is functionally constrained?
DNA changes have increased effects on protein structure and fitness.
Why do functionally constrained genes have slower tick rates?
Because it is less likely a mutation will be neutral.
The molecular clock can be used to infer speciation rates and divergence times. True or false?
True.
Give the 3 assumptions of the molecular clock.
- Genetic drift is constant
- Mutation rate is constant
- Selection is constant
The molecular clock assumes genetic drift is constant. Why is this not always true?
Drift is stronger in small populations, so small/large populations vary.
The molecular clock assumes mutation rate is constant. Why is this not always true?
Mutation is affected by metabolism: higher metabolism = more oxidative damage. Also species with faster generation times (more meiotic divisions) have higher tick rates.
The molecular clock assumes selection is constant. Why is this not always true?
Adaptive bursts, e.g. in response to a new food source, and gene duplication alter the rate of selection.
The molecular clock does not always give a linear mutation-fixation rate. What causes a curvilinear relationship?
Multiple substitutions over time. When all effectively neutral changes have been made, further changes will not increase divergence.
In what codon position do most DNA changes occur?
The first codon position.
If the DNA change is to the third codon position, the effect is likely to be?
Neutral
Why does fossil evidence tend to cause an underestimate of divergence times? Give 2 reasons.
- There is a lag between DNA change and a manifestation in the phenotype.
- 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
Why is looking at molecular change a more accurate estimate of divergence times?
Because a change to DNA is the first thing to occur in speciation.
What is Dn/Ds?
The relative rate of functional evolution.
Dn = non-synonymous coding mutation Ds = synonymous non-coding mutation
What does it mean if Dn/Ds
DNA changes are deleterious and removed by purifying selection.
What does it mean if Dn/Ds > 1?
DNA changes are advantageous and fixed by positive selection.
What can be said about the functional evolution rate if a pathogen changes host?
It is high.
The functional evolution rate does not differentiate between what?
Relaxed or positive selection.
What is Pn/Ps?
The polymorphism rate.
Define the MacDonald-Kreitman (MK) test.
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.
How does gene duplication occur at meiosis?
Can result from misaligned chromosomes at recombination, leading to unequal crossing over.
Gene duplication is an extremely important mechanism in speciation. It is a common event. True or false?
False: it is v. rare.
Duplicated genes have 3 different fates. What are they?
- Neofunctionalisation: develop an entirely new function
- Subfunctionalisation: duplicates each take on a singular function from the ancestral multifunctional gene
- Pseudogenes arise from an accumulation of mis-sense mutations, resulting in gene death. The pseudogene is the residual nucleotide sequences left in the genome.
What is dosage sensitivity?
Some genes are dosage sensitive in that they have an increased/descreased fitness effect based on copy number.
