Midterm 2 - Notes 3 (Part 2)

Question 1

What are modules?

Answer 1

Any functionally discrete portion of a locus

Question 2

What are 3 examples of modules?

Answer 2

1. Cis regulatory element
2. Protein domain (exon)
3. Alternative splice site

Question 3

What does redundancy imply?

Answer 3

That both genes have the same function

- cant be maintained over long evolutionary period

Question 4

What is the most common fate of duplication?

Answer 4

Loss of function

- degeneration of a copy (can occur after of during duplication)

Question 5

Sub-functionalization

Answer 5

Is a neutral mutation process in which each paralog retains a subset of its original ancestral gene

• degeneration of different modules in each copy (LOF)
• different functions are maintained after duplication

Question 6

What do the duplicated genes in sub-functionalization do?

Answer 6

Together they fulfill the function of the original gene

• maintaining (purifying) selection acts on both copies
• allows for further specialization of functions

Question 7

What is assumed in sub-functionalization?

Answer 7

Original gene contains multiple functions

Question 8

What kind of selection does sub-functionalization use?

Answer 8

Purifying selection

Question 9

Purifying selection

Answer 9

Is the selective removal of alleles that are deleterious

- selective pressures to maintain existing functions

Question 10

Neo-functionalization

Answer 10

Is the perspective that all integration is the result of past integration

• evolution of new modules in one copy (one copy stays the same)
• the other copy acquires a new function

Question 11

When may neo-functionalization occur?

Answer 11

Either during or after duplication

Question 12

What kind of selection does neo-functionalization use?

Answer 12

Positive selection

Question 13

Positive selection

Answer 13

Is the process by which new advantageous genetic variants sweep a population

Question 14

How does neo-functionalization get a new gene copy?

Answer 14

Through translocation

Question 15

Genome mining

Answer 15

Refers to deriving various information about the organism based on genome analysis

Question 16

Sequence analysis

Answer 16

Is the process of subjecting a DNA, RNA or peptide sequence to nay of a wide range of analytical methods to understand its features, functions, structure or evolution

Question 17

Expression profiling

Answer 17

Is the measurement of the activity of thousands of genes at once, to create a global picture of cellular function

Question 18

What is intronnless and example of?

Answer 18

Hallmark

Question 19

What were the steps for the retro-copies experiment? (6)

Answer 19

1. Started off with a collection of all protein coding sequences (not the introns), including pseudogenes
   - included known function of protein function sequences and suto regions
2. Used a set of mRNA sequences and performed a similar search against complete human genomes
3. Found 4 hits without gaps
4. This gave them a collection of all intronless genes in the human genome which would be candidates for retro copies
   - this means that not all intronless genes are retro copies (which is why they looked further)
5. Took the candidates and did a similar sequence search but included the introns in the search
   - looked fro additional hits that had gaps (at least 50% similar –> paralog)
6. Found 3,951 putatuve retro-copies
   - of these, 705 (18%) were intact (the rest were pseudogenes

Question 20

What does it mean if they found no gaps in their hit?

Answer 20

That no introns were in the sequence

- because introns creates gaps

Question 21

What did it mean when they found intact sequence? (2)

Answer 21

1. No premature stop codons

2. No frame shift mutations

Question 22

Ks

Answer 22

Silent sites

Question 23

Silent sites

Answer 23

Not changing encoded amino acids

- change DNA sequence though (but not the function)

Question 24

Why should silent mutations accumulate over evolution?

Answer 24

Because they are under no selection and should accumulate over time based on mutation rate

Question 25

Orthologs

Answer 25

Genes in a given species that evolved from a common ancestral gene by speciation

• retain same function
• results in 2 different species

Question 26

Paralogs

Answer 26

The relationship between genes originating via genetic duplication

• results from same organism
• duplication

Question 27

What Ks does most retro-copies have in humans?

Answer 27

0.05-0.25

Question 28

What is Ks proportional to?

Answer 28

Time

Question 29

Why does the curve decrease?

Answer 29

Because retro-copies became so dis-similar they were unable to be identified
- loss of retro-copies over time

Question 30

What do primates diverge from?

Answer 30

Other mammals

Question 31

What are 4 assumptions in the evolutionary fate to retry-copies?

Answer 31

1. The new regulatory elements the retroposom gained drive new expression pattern (may allow neo-functionalization)
2. If the duplicated is not important then the coding region of the retro copy should evolve neutrally
   - eventually become a processed pseudogene
3. If the functionality of the original protein is adaptively important in both the old and the new is it expressed in the coding region and both should be under purifying selection
4. If the duplicate in addition to its new expression also changes is protein function then the coding region of the retro-copy should be under positive selection
   - coding region of parent should be under purifying selection