w3 L1 positive selection and gene duplication: dN/dS Flashcards
What is dN and dS
dN is changes in non-synonymous site
dS is changes per synonymous site (silent mutation)
The number non-synonymous sites does not equal # synonymous Due to different in fold mutation
Why is dN/dS interspersed (spread out )
-control for lineage (taxa) effects
-control for regional mutation biases
Why is there more dS than dN
Synonymous sites are evolving faster
Synonymous sites rates show less variance because less heterogeneity in selective constraint
dN<dS purifying selection
-changes that affect the amino acid sequences
When does dN=dS
In pseudogene
Circumstances which dN>dS
Complex in our immune system that is infamously variable. Arm race against pathogen
dN/dS calculation
Paralogs and Orthologs
Paralogs-genes whose lineages diverged at a gene duplication event
Orthologs-genes whose lineages diverged at a speciation event
Gene Duplication by Retrotransposition
A mRNA can be reverse transcripted and inserted back to the genome
-the reinserted gene in know as retrocopy, usually considered a processed pseudogene. Contain a poly a tail, does not have intron and it’s found in an odd location
Ohno’s Model of Gene Duplication
-when we have 2 copy of a gene, the second gene is free to accumulate mutation
-these mutation can be inactivation mutation, turning it into a pseudo-gene
-they can also be beneficial mutation which lead to new fuction
How do you tell whether the extra copy is a pseudogene?
-After a certain level of divergence we expect inactivating mutations to arise as Frameshifts or nonsense mutations
- the expected dN=dS, exon=intron
jingwei example
-working on Adh-like gene in D.teissieri and D.yakuba not interrupted by introns
* Polymorphic and divergent sites are mainly at “synonymous sites”
-found 3 extra exon upstream
-this gene seams to be a chimeric gene arose 2mya
example of gene getting new function : neofunctionalization: RNA1B
-in Douc langur (monkey) have 2 copy of the gene RNASE1
- one gene gain a new fuction for digestion, having a pH optima of 6.3, from 7.4. DS RNA digestion->RNA digest. Move from the pancreas to small intestine
Fate of duplicated gene: specialisation
-both gene have degenerative mutation which are complementary to each other
-both gene needed to fuction
Degenerate mutations increase the maintenance of duplicates
engrailed gene of zebra fish
-eng1 code for pectoral fin bud
-eng1b code for hindbrain
But ancestral strain En1 code for both