Flashcards in Lecture 4 Deck (26):
- A metric to measure evolution, this controls for lineage effects (taxa) and regional mutation biases.
Changes per non-synonymous site
Changes per synonymous site
dN is usually less than dS, why?
- Synonymous sites are evolving faster, because there is more purifying selection acting on non-synonymous sites
- Synonymous site rates show less variance because there is less heterogeneity in selective constraint
dN < dS
- Purifying selection
dN = dS
- Neutrally evolving
dN > dS
- Diversifying selection (a type of adaptive selection)
- More aa site changes that synonymous site changes.. eg) parts of the MHC complex, viral coat proteins, mating associated loci.
Similarity between two sequences due to that fact that they arose from the same ancestral sequence
Genes who lineages diverged at a gene duplication event
Genes whose lineages divgered at a speciation event.
Gene dupication events arise via:
- Unequal crossing-over
- Duplication of a whole genome
Unequal crossing over:
Genetic material between non-sister chromatids during the prophase I of meiosis.
- dsDNA gene is transcribed to a primary transcript with introns spliced out and poly-A tail is attached. Sometimes reverse transcription occurs, and the transcript is randomly integrated back into the genome.
How can you identify retrocopies?
- Long poly-A tail
- Randomly found in the genome
- No introns
Ohno's model of gene duplication:
- A gene is duplicated and mutations can occur where ever in the new gene, as it is an extra, unnecessary copy
- A mutation that inactivates the sequence may occur, or a beneficial mutation may occur with a positive function
How can you tell if an extra copy of a gene is a pseudogene:
- After a certain level of divergence frameshift/nonsense mutations start arising
- dN/dS ratio of 1
Jingwei - the reincarnated princess:
An Adh-like sequence in flies not interupted by introns - maybe a pseudogene arisen by retrotransposition
- Polymorephic and divergent sites are mainly at 'synonymous sites' so dN
- Three upstream exons
- This function formed a novel chimeric gene
- A possible fate of a duplicated gene due to the addition of a beneficial mutation
Neofunctionalisation in columbine monkeys:
A gene duplication event in RNASE, a gene present in the pancrease and small intestine
- The ancestral copy digests dsRNA in lots of tissues with a pH optima of 7.4
- The new copy is expressed in the small intestine with a pH optima of 6.3, due to mutations optimising the new RNASE1B gene.
- An ancestral gene with multiple functions splits into specialised functions after a gene duplication event.
- Complementary degenerative mutations eg) in regulatory elements, which are often modular
- Increase the maintenance of duplicates.
Subfunctionalisation in Zebra fish:
- gng1 gene expressed in pectoral buds, and eng1b is expressed in spinal neurons
- In mice ancestor this gene is expressed in both places.
Saccharomyces gene duplicates of Sir3P and ORC1:
Sir3p and ORC1 are paralogs, not functionally equivalent.
- Adding an ancestral sequence rescues for knockouts of either gene.
- The ancestral sequence has both functions, and the gene duplication event lead to subfunctionalisation
- Mutants viable but sterile
- Part of a similar complex that silence mating-type loci
- Essential for viability
- Part of the origin of replication complex
Paralogs in a nematode genome:
- Plotting substitutions/replacement site vs. substitutions/silent site
- If everything is evolving neutrally we would expect everything to lie on the line of 1.
- The further you go in evolutionary time, the more functions have derived and more purifying selection occurs