Molecular clock

Question 1

What do class 1 antigens do?

Answer 1

Bind foreign bodies and present to cytotoxic killer cells

Question 2

Give examples of class 1 antigen loci

Answer 2

HLA-A
HLA-B
HLA-C
(All in the MHC complex)

Question 3

Platyfish are viviparous, true or false?

Answer 3

True

Question 4

What is meant by vivparous?

Answer 4

Organisms bear live young

Question 5

What is the significance of the platyfish genome sequence?

Answer 5

It was the first genome from an non-mammalian viviparous vertebrate

Question 6

Does the alcohol dehydrogenase gene show geographical clines in Drosophila melanogaster?

Answer 6

Yes

Question 7

What are neutrality tests?

Answer 7

Statistical tests for departures from neutrality

Question 8

Why are neutrality tests useful?

Answer 8

Very useful as they detect the signatures of natural selection

Question 9

mps5 is not temperature sensitive, true or false?

Answer 9

False, it is extremely temperature sensitive

Question 10

Are clocks adaptive?

Answer 10

Yes - ubiquity

Question 11

Is the mammalian clock the same as that of Drosophila?

Answer 11

Very similar

Question 12

Is the ls-tim circadian clock more or less light-sensitive?

Answer 12

Less light-sensitive

Question 13

Is ls-tim an old or new mutation?

Answer 13

A new mutation that has spread from southern Italy by directional selection in 8000 years

Question 14

If ls-tim shows opposite latitudinal relationship in Iberia compared to Italy with higher ls-tim levels in the north, what type of selection does this support?

Answer 14

Directional selection NOT balancing selection

Question 15

What does microsatellite analysis suggest what the dominant force driving ls-tim spread is?

Answer 15

Selection

Question 16

Light stimulation is conveyed to tim via what molecule?

Answer 16

Cryptochrome

Question 17

What happens when tim physically interacts with cry under ‘lights on’?

Answer 17

It leads to rapid tim degradation

Question 18

What happens to the physical interaction between l-tim and cry in light conditions?

Answer 18

It is attenuated

Question 19

Which is more stable, ls-tim or s-tim?

Answer 19

ls-tim

Question 20

In summary, what do period Thy-Gly repeats reveal?

Answer 20

Balancing selection and underlying functional biology

Question 21

In summary, timeless provides a rare case of what type of selection?

Answer 21

Directional selection favouring a new allele that we can understand at the phenotypic and molecular levels

Question 22

In summary, what maintains the fast/slow polymorphism in Adh?

Answer 22

Unknown

Question 23

In 1962, Zuckerkandl and Pauling compared different species protein sequences. What did they suggest was the best indicator of amino acid variability?

Answer 23

Time of divergence since common ancestry (irrespective of mutation rates across genes or species)

Question 24

What did the ‘molecular clock’ idea stimulate Kimura to develop in 1969?

Answer 24

The ‘neutral theory’ of molecular evolution (most DNA variation is selectively neutral, and is either eliminated or fixed by drift)

Question 25

Is natural intraspecific genetic variation obvious or subtle?

Answer 25

Usually subtle, and phenotypes are usually difficult or impossible to detect

Question 26

Intraspecific variation is the substrate for generating what?

Answer 26

Interspecific variation

Question 27

Over an entire gene, what is the value of Ka/Ks usually?

Answer 27

Small, but over sections can be >1 suggesting natural selection in a specific region

Question 28

When testing for natural selection, what provides the raw material?

Answer 28

Modern genome biology, i.e. DNA sequences

Question 29

When testing for natural selection, what theory provides the null hypothesis of all statistical tests of population variability?

Answer 29

Kimura's theory (after years of controversy)

Question 30

Why, for most proteins, is Ka/Ks small, i.e. Ks>>>Ka?

Answer 30

Because of selective constraints on protein sequence

Question 31

If all codons had 4-fold degeneracy, then the 3rd (synonymous) position would be free from selective constraints. Why is this not true in practice?

Answer 31

Because of codon bias

Question 32

If you compare the DNA from two related species, what would you see in terms of substitutions?

Answer 32

Lots of substitutions at non-coding regions (e.g. introns) and synonymous sites (Ks) of coding region. Far fewer substitutions in non-synonymous sites (Ka) because of selective constraints

Question 33

What can we infer if Ka/Ks ~1?

Answer 33

Suggests no selective constraints (any amino acid is okay, i.e. drift)

Question 34

What can we infer if Ka/Ks >1?

Answer 34

Rapid amino acid evolution - suggests positive selection

Question 35

What can we infer if Ka/Ks is small?

Answer 35

Suggest amino acid evolution is under constraint - stabilising selection

Question 36

How many genes show positive selection throughout their sequence?

Answer 36

Very few | Some defence response, proteolysis genes

Question 37

What is the most 'clinal' site of the alcohol dehydrogenase gene?

Answer 37

Adh fast/slow (AdhF/S) | Consistent with selection at that site

Question 38

What two tests are commonly used to test natural selection using interspecific comparisons?

Answer 38

HKA test | MacDonald Kreitman test

Question 39

What do both the HKA and MacDonald Kreitman tests both use?

Answer 39

The neutral theory for the NH which predicts 'the amount of within species variation found at a locus, should correlate with the amount of between species variation at that locus'

Question 40

When natural selection on human protein coding genes was investigated, how many out of the 11,624 genes showed coding variation?

Answer 40

10,767

Question 41

What sort of proteins in the human genome show hallmarks of both balancing and directional selection?

Answer 41

Defence proteins

Question 42

Since when did insects start to evolve resistance to pyrethroid insecticides?

Answer 42

Since 1980s, e.g. tobacco budworm, Heliothis verescens in USA

Question 43

Neutrality tests are now web-based, true or false?

Answer 43

True

Question 44

In the tajima test, what does it mean if D is not zero?

Answer 44

Selection is at work

Question 45

In the tajima test, what does it mean if D is negative?

Answer 45

Suggests directional selection (too many singletons - young neutral variation at low frequencies)

Question 46

In the tajima test, what does it mean if D is positive?

Answer 46

Suggests balancing selection (too much variation, i.e. high levels of few variants)

Question 47

What does FST measure?

Answer 47

The amount of genetic variation that can be explained by population structure

Question 48

What does an FST value of 0 mean?

Answer 48

Complete interbreeding

Question 49

What does an FST value of 1 mean?

Answer 49

Complete lack of interbreeding

Question 50

What kinds of natural interspecific variation is there in the Drosophila Thr-Gy region of period?

Answer 50

Normal Thr-Gly repeats | Thr-Gly replaced by pentapeptide repeat

Question 51

Is there a relationship between length differences and protein divergence (Ka)?

Answer 51

Yes

Question 52

Is the relationship between length differences and protein divergence simply due to the time elapsed since the two species had a common ancestor?

Answer 52

No, because if it were, the same correlation would be obtained with the third position (Ks), which is a measure of time elapsed since common ancestor and the ticking of the molecular clock. Thus protein divergence in flanking regions either drives length differences in repeat or vice-versa, i.e. coevolution

Question 53

What does the delay between the period and timeless mRNA and protein suggest about their interactions?

Answer 53

Suggests a negative feedback loop

Question 54

If the frequency of ls-tim correlates with the distance from southern Italy, what can we deduce about the mutation?

Answer 54

That Novoli is the epicentre of the mutation

Question 55

Why is ls-tim not seen across the whole of Europe yet?

Answer 55

Because the mutation is too young

Question 56

What is the previous estimation of the age of the newly derived allele ls-tim?

Answer 56

10-15,000 years

Question 57

What was used as the outgroup to come up with the previous estimation of the age of the newly derived allele ls-tim?

Answer 57

D. simulans