Lecture 4

Question 1

dN/dS =

Answer 1

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

Question 2

dN =

Answer 2

Changes per non-synonymous site

Question 3

dS =

Answer 3

Changes per synonymous site

Question 4

dN is usually less than dS, why?

Answer 4

• 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

Question 5

dN < dS

Answer 5

• Purifying selection

Question 6

dN = dS

Answer 6

• Neutrally evolving

Question 7

dN > dS

2

Answer 7

• 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.

Question 8

Homolgy:

Answer 8

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

Question 9

Paralogs:

Answer 9

Genes who lineages diverged at a gene duplication event

Question 10

Orthologs:

Answer 10

Genes whose lineages divgered at a speciation event.

Question 11

Gene dupication events arise via:

Answer 11

• Unequal crossing-over
• Retrotransposition
• Duplication of a whole genome

Question 12

Unequal crossing over:

Answer 12

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

Question 13

Retrotransposition:

Answer 13

• 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.

Question 14

How can you identify retrocopies?

Answer 14

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

Question 15

Ohno’s model of gene duplication:

Answer 15

• 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

Question 16

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

Answer 16

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

Question 17

Jingwei - the reincarnated princess:

Answer 17

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

Question 18

Neofunctionalization:

Answer 18

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

Question 19

Neofunctionalisation in columbine monkeys:

Answer 19

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.

Question 20

Subfunctionalistion:

Answer 20

• 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.

Question 21

Subfunctionalisation in Zebra fish:

Answer 21

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

Question 22

Saccharomyces gene duplicates of Sir3P and ORC1:

Answer 22

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

Question 23

Sir3p:

Answer 23

• Mutants viable but sterile

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

Question 24

ORC1:

Answer 24

• Essential for viability

- Part of the origin of replication complex

Question 25

Paralogs in a nematode genome:

Answer 25

- 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

Question 26

Humans and chimps have diverged by:

Answer 26

- 1% in align-able regions | - 60 000 amino acids