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Flashcards in Lecture 4 Deck (26)
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1
Q

dN/dS =

A
  • A metric to measure evolution, this controls for lineage effects (taxa) and regional mutation biases.
2
Q

dN =

A

Changes per non-synonymous site

3
Q

dS =

A

Changes per synonymous site

4
Q

dN is usually less than dS, why?

A
  • 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
5
Q

dN < dS

A
  • Purifying selection
6
Q

dN = dS

A
  • Neutrally evolving
7
Q

dN > dS

2

A
  • 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.
8
Q

Homolgy:

A

Similarity between two sequences due to that fact that they arose from the same ancestral sequence

9
Q

Paralogs:

A

Genes who lineages diverged at a gene duplication event

10
Q

Orthologs:

A

Genes whose lineages divgered at a speciation event.

11
Q

Gene dupication events arise via:

A
  • Unequal crossing-over
  • Retrotransposition
  • Duplication of a whole genome
12
Q

Unequal crossing over:

A

Genetic material between non-sister chromatids during the prophase I of meiosis.

13
Q

Retrotransposition:

A
  • 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.
14
Q

How can you identify retrocopies?

A
  • Long poly-A tail
  • Randomly found in the genome
  • No introns
15
Q

Ohno’s model of gene duplication:

A
  • 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
16
Q

How can you tell if an extra copy of a gene is a pseudogene:

A
  • After a certain level of divergence frameshift/nonsense mutations start arising
  • dN/dS ratio of 1
17
Q

Jingwei - the reincarnated princess:

A

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<dS
  • Three upstream exons
  • This function formed a novel chimeric gene
18
Q

Neofunctionalization:

A
  • A possible fate of a duplicated gene due to the addition of a beneficial mutation
19
Q

Neofunctionalisation in columbine monkeys:

A

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.
20
Q

Subfunctionalistion:

A
  • 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.
21
Q

Subfunctionalisation in Zebra fish:

A
  • gng1 gene expressed in pectoral buds, and eng1b is expressed in spinal neurons
  • In mice ancestor this gene is expressed in both places.
22
Q

Saccharomyces gene duplicates of Sir3P and ORC1:

A

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
23
Q

Sir3p:

A
  • Mutants viable but sterile

- Part of a similar complex that silence mating-type loci

24
Q

ORC1:

A
  • Essential for viability

- Part of the origin of replication complex

25
Q

Paralogs in a nematode genome:

A
  • 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
26
Q

Humans and chimps have diverged by:

A
  • 1% in align-able regions

- 60 000 amino acids