Molecular phylogenies 4: detecting selection Flashcards
Can we use trees to detect selection?
Demographic and selective pressure can generate similair patterns so we cannot just look at tree shape
Examples:
Population growth and selective sweeps both have reducing coalescents towards the present day.
Population subdivision and balancing selection both have two long internal branches.
Overview of methods to detect selection.
Compare silent and replacement mutations within genes
-> Dn/Ds method
-> McDonald Kreitman test
Look at convergently evolving populations.
Look at the different genetic diversities, tree shapes, or mutation frequencies among genes or along chromsomes.
Looking at linked genetic variation to selective gene
Hard sweeps occur when an advantageous allele sweeps through the population.
There is little genetic diversity around this gene as these genes are secondarily selected for—hitchhiking genes.
Genetic recombination can break up this linkage.
-> Regions, where there are rapid sweeps, have less diversity as less time from recombination
Soft sweeps can also occur but there is more variation within and around the gene.
Example: Reduction in genetic diversity around dhfr locus in Plasmodium falciparum malaria. (drug-resistant gene)
Example: Reduction in genetic dievrsity around gene leading to lactose tolerance (LPH enzyme from LCT gene)
Example: ~13% of amino acid substitutions are thought to have resulted in selective sweeps in Drosophila
Dn/Ds method
Relative rates of mutations: Non-S mutations/ S mutations
> 1: positive selection has occurred as there are more non-s mutations than S mutations
<1: negative selection has occured as more S mutations that Non-S mutations.
=1: Neutral selection as there is the same amont of synonymous and non-S mutations.
This method should be applied to codons rather than whole genes as only a few codons are selected for -> overall there is more constraint than there is positive selection within genes so Dn/Ds<1.
Example: Dn/Ds>1 in codons for the active sites of many enzymes.
Example: FOXP2 gene important for language and mutations associated with language disorders. Mutations associated with facial movement. Models of FOXP2 protein evolution (dN/dS sites analysis) show evidence of strong purifying selection across the polypeptide
Silent mutations may not be neutral
Overlapping genes and alternative reading frames (e.g. 90% of HIV overlaps)
Regulatory sequence elements
Affect stability of RNA/mRNA/ DNA structure due to nucleotide pair bonding
Codons for same amino acid differ in fitness (codon usage bias)-> different codons have different abundance of tRNA or translation efficiencies.
McDonal Kreitman Test
This test compares the ratio of fixed synonymous: fixed non-synonymous to polymorphic synonymous: polymorphic non-synonymous. -> requires species to have related outgroup
Fixed: allele fixed between species and outgroup
Polymorphic: allele different between species and outgroup
Advatagous: tend to be in routes so fixed
Deleterious: tend to be at tips so polymorphic
Compare ratio of silent: replacement fixed sites to ratio of silent: raplacement polymorphic sites.
higher ratio of replacement fixed suggests positive selection
higher ratio of synonymous fixed suggests purifying selection
If the ratios are the same then there is no selection and both types of site are effected by drift.
Example: This was done to show adaptive evolution in the Drosophila Adh gene
The estimate of adaptive evolution is biased downwards by presence of slightly deleterious mutations
- Solution: remove low frequency polymorphisms from the analyses
- Analyses suggests that adaptive evolution has been underestimated in bacteria and Drosophila
- Also suggests that adaptive evolution could be prevelant in humans (>8%) but not detectable.
Convergent evolution
If the same mutation is fixed in two convergently evolving populations/ different parts of the lineage, this suggests selection.
Example: Lysozyme is an antibacterial enzyme in saliva and the same mutation has occured in many species. (D75 and N87)
Example: the monarch butterfly caterpillar, the red milkweed beetle, oleander aphids and the large milkweed beetle, have all evolved to feed on poisonous milkweed plants through parallel mutations in the (Na++K+) ATPase gen
