Molecular clock Flashcards
What do class 1 antigens do?
Bind foreign bodies and present to cytotoxic killer cells
Give examples of class 1 antigen loci
HLA-A
HLA-B
HLA-C
(All in the MHC complex)
Platyfish are viviparous, true or false?
True
What is meant by vivparous?
Organisms bear live young
What is the significance of the platyfish genome sequence?
It was the first genome from an non-mammalian viviparous vertebrate
Does the alcohol dehydrogenase gene show geographical clines in Drosophila melanogaster?
Yes
What are neutrality tests?
Statistical tests for departures from neutrality
Why are neutrality tests useful?
Very useful as they detect the signatures of natural selection
mps5 is not temperature sensitive, true or false?
False, it is extremely temperature sensitive
Are clocks adaptive?
Yes - ubiquity
Is the mammalian clock the same as that of Drosophila?
Very similar
Is the ls-tim circadian clock more or less light-sensitive?
Less light-sensitive
Is ls-tim an old or new mutation?
A new mutation that has spread from southern Italy by directional selection in 8000 years
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?
Directional selection NOT balancing selection
What does microsatellite analysis suggest what the dominant force driving ls-tim spread is?
Selection
Light stimulation is conveyed to tim via what molecule?
Cryptochrome
What happens when tim physically interacts with cry under ‘lights on’?
It leads to rapid tim degradation
What happens to the physical interaction between l-tim and cry in light conditions?
It is attenuated
Which is more stable, ls-tim or s-tim?
ls-tim
In summary, what do period Thy-Gly repeats reveal?
Balancing selection and underlying functional biology
In summary, timeless provides a rare case of what type of selection?
Directional selection favouring a new allele that we can understand at the phenotypic and molecular levels
In summary, what maintains the fast/slow polymorphism in Adh?
Unknown
In 1962, Zuckerkandl and Pauling compared different species protein sequences. What did they suggest was the best indicator of amino acid variability?
Time of divergence since common ancestry (irrespective of mutation rates across genes or species)
What did the ‘molecular clock’ idea stimulate Kimura to develop in 1969?
The ‘neutral theory’ of molecular evolution (most DNA variation is selectively neutral, and is either eliminated or fixed by drift)
Is natural intraspecific genetic variation obvious or subtle?
Usually subtle, and phenotypes are usually difficult or impossible to detect
Intraspecific variation is the substrate for generating what?
Interspecific variation
Over an entire gene, what is the value of Ka/Ks usually?
Small, but over sections can be >1 suggesting natural selection in a specific region
When testing for natural selection, what provides the raw material?
Modern genome biology, i.e. DNA sequences
When testing for natural selection, what theory provides the null hypothesis of all statistical tests of population variability?
Kimura’s theory (after years of controversy)
Why, for most proteins, is Ka/Ks small, i.e. Ks»>Ka?
Because of selective constraints on protein sequence
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?
Because of codon bias
If you compare the DNA from two related species, what would you see in terms of substitutions?
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
What can we infer if Ka/Ks ~1?
Suggests no selective constraints (any amino acid is okay, i.e. drift)
What can we infer if Ka/Ks >1?
Rapid amino acid evolution - suggests positive selection
What can we infer if Ka/Ks is small?
Suggest amino acid evolution is under constraint - stabilising selection
How many genes show positive selection throughout their sequence?
Very few
Some defence response, proteolysis genes
What is the most ‘clinal’ site of the alcohol dehydrogenase gene?
Adh fast/slow (AdhF/S)
Consistent with selection at that site
What two tests are commonly used to test natural selection using interspecific comparisons?
HKA test
MacDonald Kreitman test
What do both the HKA and MacDonald Kreitman tests both use?
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’
When natural selection on human protein coding genes was investigated, how many out of the 11,624 genes showed coding variation?
10,767
What sort of proteins in the human genome show hallmarks of both balancing and directional selection?
Defence proteins
Since when did insects start to evolve resistance to pyrethroid insecticides?
Since 1980s, e.g. tobacco budworm, Heliothis verescens in USA
Neutrality tests are now web-based, true or false?
True
In the tajima test, what does it mean if D is not zero?
Selection is at work
In the tajima test, what does it mean if D is negative?
Suggests directional selection (too many singletons - young neutral variation at low frequencies)
In the tajima test, what does it mean if D is positive?
Suggests balancing selection (too much variation, i.e. high levels of few variants)
What does FST measure?
The amount of genetic variation that can be explained by population structure
What does an FST value of 0 mean?
Complete interbreeding
What does an FST value of 1 mean?
Complete lack of interbreeding
What kinds of natural interspecific variation is there in the Drosophila Thr-Gy region of period?
Normal Thr-Gly repeats
Thr-Gly replaced by pentapeptide repeat
Is there a relationship between length differences and protein divergence (Ka)?
Yes
Is the relationship between length differences and protein divergence simply due to the time elapsed since the two species had a common ancestor?
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
What does the delay between the period and timeless mRNA and protein suggest about their interactions?
Suggests a negative feedback loop
If the frequency of ls-tim correlates with the distance from southern Italy, what can we deduce about the mutation?
That Novoli is the epicentre of the mutation
Why is ls-tim not seen across the whole of Europe yet?
Because the mutation is too young
What is the previous estimation of the age of the newly derived allele ls-tim?
10-15,000 years
What was used as the outgroup to come up with the previous estimation of the age of the newly derived allele ls-tim?
D. simulans
