Lecture 20 - Gene Duplication

Question 1

Where do new genes come from?

Answer 1

Gene duplication.

Question 2

Who made the argument of “evolution by gene duplication”?

Answer 2

Susumu Ohno - proposed that each new gene must have arisen from an existing gene.

Question 3

What are the different types of DNA duplication?

Answer 3

1. Partial gene duplication
2. Whole gene duplication
3. Segmental duplication
4. Polysomy (whole chromosomal duplication)

Question 4

What is a tandem repeat?

Answer 4

A repeat that is found beside the original gene.

Question 5

What are the two major mechanisms of duplication?

Answer 5

1. Unequal crossing over
2. Transposition

Question 6

What are the two types of crossing over that we see?

Answer 6

1. Homologous unequal crossing over
2. Non-homologous unequal crossing over

Question 7

When an unequal crossing over occurs and produces tandem duplicates in the DNA strand, what do these duplicated sequences allow?

Answer 7

More opportunity for unequal crossovers (i.e., duplication encourages further duplication)!

Question 8

What is homology?

Answer 8

Similarity due to shared common descent.

Question 9

What is paralogy?

Answer 9

Homology due to DNA duplication.

Question 10

What are paralogs?

Answer 10

Paralogs are genes that started diverging due to duplication

Question 11

What is orthology?

Answer 11

Homology due to shared vertical descent.

Question 12

What are orthologs?

Answer 12

Orthologs are genes that started diverging due to a speciation event.

Question 13

What is a gene family?

Answer 13

A group of orthologous and/or paralogous genes that share a common ancestral gene.

Question 14

What is a gene superfamily?

Answer 14

Implies a more distant relationship between the gene members (might carry out very different functions).

Question 15

What is an orphan gene?

Answer 15

A gene with no homologs in other evolutionary lineages.

Question 16

What is the biggest gene family in mammals?

Answer 16

Olfactory receptors (ORs) gene superfamily.

Question 17

At what rate do duplications arise?

Answer 17

They arise spontaneously at high rates.

Question 18

In general, do gene duplications have an effect on the organisms fitness?

Answer 18

No, most of them are viable (with no change in the organisms fitness).

BUT a small fraction of duplicates are retained and even fewer evolve new functions!

Question 19

What are the potential fates of a duplicated gene?

Answer 19

1. Nonfunctionalisation (loss of function)
2. Conservation
3. Subfunctionalisation (partial loss of function)
4. Neofunctionalisation (novel function)

Question 20

What is nonfunctionalisation?

Answer 20

Gene loss, resulting in a non-processed pseudogene (i.e., does not undergo RNA processing).
- The most likely fate of a duplicated gene
- Duplicated gene becomes “redundant”

Question 21

What is neofunctionalisation?

Answer 21

Where over time, the duplicated gene accumulates mutations that allows it to acquire a novel function.

Question 22

What is neofunctionalisation?

Answer 22

Where over time, the duplicated gene accumulates mutations that allows it to acquire a novel function.

Question 23

Give an example of neofunctionalisation in humans.

Answer 23

GLUD2 gene (a duplicate of GLUD1) - which encodes the enzyme that helps us recycle glutamate (a hugely important neurotransmitter in the brain).

Question 24

What is subfunctionalisation?

Answer 24

Genes that are multifunctional (i.e., encode several products) can divide up these functions after duplication.

Can involve…
- Complementary loss of sub-function
- Specialisation of different copies in different tissues/developmental stages
- Escape from adaptive conflict

Question 25

Why might duplicates be conserved (i.e., retain the same function as the original)?

Answer 25

Often caused by selection for gene dosage (the more gene product the better, thus having more copies of the gene is advantageous).
- E.g., Esterase B which confers insecticide resistance, strong selection for more copies of this gene (i.e., esterase repeats evolve)

Question 26

How can we date duplication events directly?

Answer 26

Can be done by estimating the rate of substitution (r) for duplicate genes.

Question 27

What do we need in order to estimate the rate of substitution (r) for specific duplicated genes?

Answer 27

We need a calibration point. Thus we can use…
1. Time of speciation (Ts, of a known speciation event)
2. Number of substitutions per site between the species (K)

From this, we can get the average rate.
(SEE LECTURE 20 (part 2) @ 6:30 FOR FORMULA)

Question 28

How are our olfactory receptor (OR) genes evolving?

Answer 28

Through an extremely rapid process of birth-and-death evolution - with high rates of duplication, neofunctionalisation, and gene loss.

Question 29

What differentiation can we make by looking at the abundance of OR sequences in aquatic and terrestrial vertebrates?

Answer 29

Huge number of alpha- and gamma-subfamilies in terrestrial animals but little or none in aquatic animals.
- Tells us that these subfamilies have specialised to detect airborne odours.

The other 5 OR subfamilies are found in great numbers in aquatic vertebrates but little or none in terrestrials.
- Tells us that these subfamilies have specialised to detect water-soluble odours.