Lecture 4 Flashcards Preview

Evolutionary Genetics and Genomics > Lecture 4 > Flashcards

Flashcards in Lecture 4 Deck (26):
1

dN/dS =

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

2

dN =

Changes per non-synonymous site

3

dS =

Changes per synonymous site

4

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

5

dN < dS

- Purifying selection

6

dN = dS

- Neutrally evolving

7

dN > dS
(2)

- 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

Homolgy:

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

9

Paralogs:

Genes who lineages diverged at a gene duplication event

10

Orthologs:

Genes whose lineages divgered at a speciation event.

11

Gene dupication events arise via:

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

12

Unequal crossing over:

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

13

Retrotransposition:

- 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

How can you identify retrocopies?

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

15

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

16

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

17

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

18

Neofunctionalization:

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

19

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.

20

Subfunctionalistion:

- 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

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.

22

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

23

Sir3p:

- Mutants viable but sterile
- Part of a similar complex that silence mating-type loci

24

ORC1:

- Essential for viability
- Part of the origin of replication complex

25

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

26

Humans and chimps have diverged by:

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