Quantification of Natural Selection

Question 1

Substituting N

Answer 1

AAT encoding asparagine (Asp/N)

Mutational possibilities:
- CAT, GAT, TAT
- ACT, AGT, ATT
- AAA, AAC, AAG

Giving amino acids:
- H, D, Y
- T, S, I
- K, N, K

Question 2

Synonymous vs non-synonymous

Answer 2

Synonymous substitutions do not change the amino acid

Non-synonymous substitutions change the amino acid

Ratio of non-syn/syn = dN/ds = omega

Question 3

Are most AAT mutations synonymous or non-synonymous?

Answer 3

Non-synonymous, they will change the amino acid

Question 4

Define constraint

Answer 4

Selective pressure to maintain protein sequence

Question 5

Define neutrality

Answer 5

No pressure, mutations accumulate evenly

Question 6

Define positive selection

Answer 6

Selective pressure favours change in protein sequence

Question 7

What are some amino acids more prone to non-synonymous substitutions?

Answer 7

Non-redundancy (Met, Trp) or 2-fold redundancy (Asp, Glu etc)

Others have 4-fold or 6-fold redundancy (Leu, Arg, Ser)

Question 8

How many positive selection sites are there?

Answer 8

18 in total

14 are in the Hyper variable region

Question 9

Calculating omega

Answer 9

For each codon in the alignment, count potential syn (s) and potential non-syn (n)
Total up to give S and N
Count actual synonymous (Sd) and non-synonymous (Nd) substitutions
pS and pN are Sd/S and Nd /N - proportions of substitutions
Correct for multiple substitutions – dN and dS are rates of substitution: dS = -(3/4)ln(1-(4/3) pS )
 = dN /dS - can be calculated as an average or sitewise

Question 10

Natural selection at the molecular level

Answer 10

• Among many protein variants, one confers superior survival/reproductive potential on the organism in which it occurs:
• Organism may have more descendants
• Protein will be in more descendants
• There will be more of that protein variant
• Selection on the protein
• Selection on the gene

Question 11

Varieties of Natural Selection at molecular level

Answer 11

• Constraint:
• Fittest variant is one currently found in population
• Selective pressure is against novelty

Positive selection:
- Fittest variant is a new one rare in population
- Selective pressure will increase this novelty

Question 12

Aspects of positive selection at molecular level

Answer 12

• Directional selection - There is one (new) fittest variant
• Diversifying selection:
• There is no single fittest variant
• Selective pressure will increase any novelty
• “It pays to be different”

Balancing selection:
- There are two variants whose fitness depends on the frequency of the other
- Selective pressure will act to maintain a ratio

Question 13

Aspects of Neutrality and Constraint at the molecular level

Answer 13

Neutrality:
- Genetic drift: each new variant will eventually either reach fixation or go extinct, purely by chance

Constraint:
- Under positive selection, fixation is reached much faster
- The currently constrained variant (which may be fixed) must once have been novel, and would originally have been positively selected

Question 14

Adaptation

Answer 14

By cumulative action of positive selection, an organism becomes adapted to its environment (niche)

• A highly adapted species is a highly constrained one
• If the niche changes, a species becomes less adapted, and positive selection may start to appear
• If the niche is always changing rapidly, adaptation may never occur: “The Red Queen Effect”