Molecular clock Flashcards

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1
Q

What do class 1 antigens do?

A

Bind foreign bodies and present to cytotoxic killer cells

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2
Q

Give examples of class 1 antigen loci

A

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

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3
Q

Platyfish are viviparous, true or false?

A

True

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4
Q

What is meant by vivparous?

A

Organisms bear live young

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5
Q

What is the significance of the platyfish genome sequence?

A

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

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6
Q

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

A

Yes

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7
Q

What are neutrality tests?

A

Statistical tests for departures from neutrality

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8
Q

Why are neutrality tests useful?

A

Very useful as they detect the signatures of natural selection

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9
Q

mps5 is not temperature sensitive, true or false?

A

False, it is extremely temperature sensitive

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10
Q

Are clocks adaptive?

A

Yes - ubiquity

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11
Q

Is the mammalian clock the same as that of Drosophila?

A

Very similar

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12
Q

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

A

Less light-sensitive

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13
Q

Is ls-tim an old or new mutation?

A

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

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14
Q

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?

A

Directional selection NOT balancing selection

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15
Q

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

A

Selection

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16
Q

Light stimulation is conveyed to tim via what molecule?

A

Cryptochrome

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17
Q

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

A

It leads to rapid tim degradation

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18
Q

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

A

It is attenuated

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19
Q

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

A

ls-tim

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20
Q

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

A

Balancing selection and underlying functional biology

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21
Q

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

A

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

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22
Q

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

A

Unknown

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23
Q

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

A

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

24
Q

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

A

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

25
Q

Is natural intraspecific genetic variation obvious or subtle?

A

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

26
Q

Intraspecific variation is the substrate for generating what?

A

Interspecific variation

27
Q

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

A

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

28
Q

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

A

Modern genome biology, i.e. DNA sequences

29
Q

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

A

Kimura’s theory (after years of controversy)

30
Q

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

A

Because of selective constraints on protein sequence

31
Q

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?

A

Because of codon bias

32
Q

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

A

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

33
Q

What can we infer if Ka/Ks ~1?

A

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

34
Q

What can we infer if Ka/Ks >1?

A

Rapid amino acid evolution - suggests positive selection

35
Q

What can we infer if Ka/Ks is small?

A

Suggest amino acid evolution is under constraint - stabilising selection

36
Q

How many genes show positive selection throughout their sequence?

A

Very few

Some defence response, proteolysis genes

37
Q

What is the most ‘clinal’ site of the alcohol dehydrogenase gene?

A

Adh fast/slow (AdhF/S)

Consistent with selection at that site

38
Q

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

A

HKA test

MacDonald Kreitman test

39
Q

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

A

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’

40
Q

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

A

10,767

41
Q

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

A

Defence proteins

42
Q

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

A

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

43
Q

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

A

True

44
Q

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

A

Selection is at work

45
Q

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

A

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

46
Q

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

A

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

47
Q

What does FST measure?

A

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

48
Q

What does an FST value of 0 mean?

A

Complete interbreeding

49
Q

What does an FST value of 1 mean?

A

Complete lack of interbreeding

50
Q

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

A

Normal Thr-Gly repeats

Thr-Gly replaced by pentapeptide repeat

51
Q

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

A

Yes

52
Q

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

A

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

53
Q

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

A

Suggests a negative feedback loop

54
Q

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

A

That Novoli is the epicentre of the mutation

55
Q

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

A

Because the mutation is too young

56
Q

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

A

10-15,000 years

57
Q

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

A

D. simulans