Molecular evolution L1-4 Flashcards
What is molecular evolution? In what two disciplines does molecular evolution have its roots?
The evolution and change of macromolecules with time. Goal is to establish relationships between sequences - how do they evolve. Goal is to reconstruct evolutionary history.
Popular genetics which provides the
theoretical foundation for the study of
evolutionary processes.
Molecular biology which provides the empirical data.
Why are we interested in molecular evolution?
Understanding the origin and diversity of life
Understanding the relationship between the phenotype and the genotype -
What makes a modern human?
Biomedical implications - understanding diseases and ex. antibiotic resistance.
What is the Hardy Weinberg principle and why is it so important?
Hardy Weinberg equilibrium means that allele frequencies are not changing and will remain constant between generations in the absence of other evolutionary influences.
The HWE is the null hypothesis for no evolution which means that we can use it to test for deviations from it which could mean:
- Nonrandon/assortative mating
- Inbreeding
- Population structure
- Selection
- Genetic drift
What are the seven underlying assumptions of HWE?
Diploid species
Sexual reproduction
Non-overlapping generations
Random mating
Infinite population size
Allele frequencies are equal in the sexes
No mutation, migration or selection, drift
Explain how we can test if sequences are in HWE.
Let’s say we have 2 alleles A and a.
- Use genotypic frequencies (AA, Aa, aa) to get allele frequencies allele p and q.
p + q = 1
AA + Aa + aa = 1 - Use allele frequencies to get expected genotypic frequencies after one generation of random mating:
p^2 = AA (expected homozygotes)
2pq = Aa (expected heterozygotes)
q^2 = aa (expected homozygotes)
p + q = 1 - Use chi^2 test to see if expected an observed genotypic proportions differ.
p-value < 0.05 indicates that we can reject the null of HWE.
Why is it so difficult to remove rare alleles from a population through selection?
If the allele is recessive then it can hide behind the heterozygotes and the phenotype won’t show and removing them will then get difficult. If it is dominant then it will get purged out fast. The question assumes that the mutation is deleterious.
How can dominance/recessivesness influence expected response to selection?
Dominant beneficial – It will increase in frequency but it will take very long time for it to actually be fixed because it can stay recessive and still have high fitness. Evolution won’t purge out those “bad” recessive alleles that hide in the heterozygotes.
Deleterious recessive – Hard for evolution to select them out.
Recessive beneficial – will increase in frequency more slowly than the dominant beneficial but will reach fixation faster because being homozygote increase fitness.
Over dominance (heterozygote advantage) – Will increase and stabilize at intermediate frequency and will be stable there over time.
Heterozygote disadvantage – Could get lost or get fixated depending on the starting frequency. More often it is going to get lost.
What is recombination?
Exchange of genetic information in mitosis and meiosis, creating new sequences – increases genetic variation. If recombination happens in a loci with linkage equilibrium the equilibrium is broken.
What is linkage equilibrium?
Traits tend to be inherited together.
How can we measure genetic variation in sequence data? Give at least two example metrics used to measure genetic variation.
Nucleotide diversity
Segregating sites
What are the forces of genetic variation and which is the main one?
Mutations is the main force of variation.
Recombination can be mutagenic.
Migration.
Genetic drift (the process of change in allele frequency due solely to chance effects) reduces variation over time.
What determines the fate of a mutation in a finite population? What are these two factors dependent on?
Genetic drift and selection. They are both dependent on the effective population size.
Selection is more effective in large populations and then drift gets less. In a larger population selection is blind to a smaller extent – selection gets more effective and drift less effective.
What is effective population size vs census population size?
A measure of how many individuals affect what will happen in the next generation. Usually smaller than the actual census size. It is not a measure of genetic diversion but there is some correlation to it.
Census population size is the total number of individuals in a population and generally the effective population size is not as large as the census population size.
What is a common model to describe the fate of a mutation in a finite population? What are the underlying assumptions of this model?
The Wright-Fisher model. You model for what will happen in the future and it is mainly a model of what will happen due to genetic drift because it assumes that there is no selection.
You also assume: random mating, finite population size, it models haploid populations and it assumes no mutations/recombination.
Discuss similarities and differences between the Hardy-Weinberg model and the Wright-Fisher model!
Hardy Weinberg assumes infinite population size and it does not allow for drift. HW assumes diploid population.
What is the role of population size in the evolution of neutral mutations?
How do we calculate how many neutral mutations per generation we will accumulate between two sequences and the probability of fixation?
Population size does not matter for neutral mutations.
2N*mu = How many neutral mutations per generation we will accumulate between two sequences. Number of neutral mutations are equal to mutation rate because population size does not matter here.
The probability of fixation is 1 / 2N.
Discuss the difference between a mutation and a substitution!
A mutation is a new allele, (gene)substitution happens when a mutation gets fixed.
What is the prediction of the molecular clock hypothesis? List and explain some factors that may cause deviation from the molecular clock.
The hypothesis is that the substitution rate is constant within species. So if we know the divergence rate and have the number of differences we can date when the divergence happens.
The substitution rate can be different because of different mutation rates which can be caused by selection pressure (mating), different repair mechanisms for mutations, different generation times, differences in metabolic rate (usually linked to generation time).
What are models of sequence evolution? Why are they needed?
They are models that allow us to reconstruct the evolution of sequences. We tend to underestimate the real evolution because some changes are hidden. Models like jc69 ect. Help model for what we cannot see just by looking at the two sequences.
What is functional constraint?
Regions of importance will have functional constraints against evolutionary change. They can have a function they need to preserve and selection will be very high to purge all changes in that region.