Molecular Evolution Flashcards
What results in molecular evolution?
Mutations:
Non-synonymous:
• Deleterious removed by purifying selection, advantageous fixed
• E.g. Epas1 has an allele that confers advantages at high altitudes by increasing RBC production, selected in Tibetan population. Makes blood more viscous and increases heart attack risk so not selected elsewhere.
Synonymous/silent substitution
• No fitness effect- evolve neutrally through genetic drift- Neutral Theory
How does the neutral theory explain the molecular clock?
• Under genetic drift, the rate of silent mutations should be steady through time (proportional to the rate of mutation)
- μ mutation rate/gene/generation
- N population size
- 2N no. Chromosomes in diploid pop
- 2Nμ new mutations/generation
- 1/2N probability of neutral fixation
Rate of substitution: number of new mutations * fixation rate
= 2Nμ * 1/2N =μ
This means the number of fixed neutral mutations should be equal to the rate of mutation
—> predicts steady change through time: Molecular Clock
What does the molecular clock do and what can it be used for?
Generates a correlation between time since divergence and number of changes, as populations are in separate trajectories
Can be used to infer:
• Phylogenetic relationships, speciation rates, divergence times
How:
• Measure genetic distance between species
• Use number of genetic changes per unit time to convert genetic distance to divergence time
• Calibrate with known divergence time
Outline evidence for the neutral theory
- Rate of silent substitutions is higher than non-synonymous
- Among non-synonymous substitutions, changes to aa’s with similar biochemical properties is more common than those with greater effect on protein function
- Non-coding sequences such as introns and pseudogens evolve at high rate, similar to silent sites
- Genes with higher functional constraints evolve more slowly- fewer mutations are neutral
Why might the molecular clock not be accurate in predicting?
• Mutation rate assumed constant but is affected by:
- metabolic rate- more oxidative damage to DNA
- Generation time- increases number of meiotic divisions per year
• Ne assumed to be of similar magnitude at occurrence of mutation and in subsequent period of potential fixation, but:
- drastic bottleneck after mutation occurrence, fixation is more likely, tick speed is faster
• Selection assumed to be constant but deviations from molecular clock will be created by impact of selection and changes in rates of adaptation over time:
- Adaptive bursts happen- new food source
-> these known sources can be modelled and corrected for
Outline the Hawaiian Molecular Clock
- Molecular data confirm the order of colonisation of islands of increasing geological age
- Honeycreeper species of oldest islands form deepest branch of tree- disparate taxa show linear relationship between genetic divergence and time, when DNA distance is plotted against island age
Why are there disagreements between fossil ages and molecular estimates?
• Fossil evidence tends to underestimate divergence time
- time required for morphological divergence
- time required for fossil remain to occur
• Molecular evidence tends to overestimate
- coalescence- most recent common ancestor (MRCA) occurs before species split
What are the molecular signatures of adaptive change and what are they used for?
To find regions of genome that contribute to adaptive variation among species
• DN/DS- relative rate of functional evolution
- different substitution rates seen at replacement (DN) vs silent (DS) sites
- DN/DS>1 replacements advantageous- fixed by positive selection/neutral replacement
- DN/DS<1 replacements are deleterious- removed by purifying selection
• E.g. HIV surface envelope protein: branch-specific DN/DS is elevated in species with recent HIV transmission and high pathogenicity- suggests positive selection in HIV envelope protein following host shift
• CANNOT differentiate positive selection from relaxed selective constraints
What is the MacDonald-Kreitman (MK) test?
Looks for genes where divergence between species exceeds polymorphism within
• Suggests gene has evolved more rapidly than underlying mutation rate
• Evidence of adaptive evolution
• Compares DN/DS (between species) and PN/PS (within species)
What are gene duplicated and how do they arise?
Duplicated genes can result from mispairing during recombination
• 1/2 gametes normal copy number, 1/4 Lack gene, 1/4 two copies
• Has facilitated evolution of complex organisms:
- vertebrate genomes contain many gene families not present in invertebrates
- many gene duplications have occurred in early evolution of animals ~550mya
Outline the molecular evolution of gene duplicates
• Can lead to evolutionary novelties as one gene can retain original function and other can become something new
• Possible fate of gene duplications:
- pseudogene: build up of mutations leads to gene death
- subfunctionalization: copy takes over one aspect of original gene function, both copies then required to carry out original function
- neofuncrionalization: copy takes on new role entirely
E.g. duplication of RNase gene in langur resulted in a digestive enzyme RNase1B, whereas RNase1A is primarily intracellular
