L6 Positive selection and dN/dS Flashcards
dN/dS
- metric to measure evolution
- accounts for lineage effect and regional mutation bias
number of syn sites do not equal number of non-syn sites
2/3 changes would be non-syn according to the aa table
dN
changes per non-synonymous site
dS
changes per synonymous site
dN vs dS
- dN usually less than dS
- synonymous sites are evolving faster
- synonymous site rates show less variance because less heterogeneity in selective constraint
dN
purifying selection
dN = dS
neutrally evolving
dN/dS calculations
see OneNote
Paralogs
genes whose lineages diverged at a gene duplication event
Orthologs
genes whose lineages diverged at a speciation event
Molecular mechanisms of gene duplication
- unequal crossing over at meiosis
- retrotransposition: reverse transcription
- genome duplication
How can you tell if the duplication had arisen from retrotransposition or unequal cross over?
If retrotransposition:
- Presence of polyA tail
- Lack of introns
retrocopy usually considered a “processed pseudogene”
Ohno’s Model of Gene Duplication
- inactivating mutation e.g. non-sense mutation - decays over time
- beneficial mutation - new function, selected for, increases in frequency, becomes fixed, new gene born = “neofunctionalization”
Fates of duplicate genes
- pseudogene
2. new function
How do you tell whether the extra copy is a pseudogene?
Genes will accumulate mutations over time .g. frameshifts or non-sense mutations
If there is substantial divergence but no inactivation after some time after the duplication, can argue that the gene has a new function
In pseudogenes expect:
expect dN = dS
exon = intron
Jingwei gene
See OneNote
