Download Chapter 4 The role of mutation in evolution

Chapter 4 The role of mutation in evolution - OUTLINE
A. Importance of mutation - although neutral theory treats mutations as either neutral or
harmful, a small fraction of mutations must also be beneficial. Important source of
genetic variation. No mutation = no evolution.
B. Types of mutation
1. Types – base substitution and various structural mutations (insertion, deletion,
inversion, translocation
2. Example of inversions on Drosophila chromosomes – stain and observe banding;
banding patterns vary. Regions with inversion in heterozygote protected from
recombination.
3. A careful look at base substitutions – alteration of one base (A,C,G,T) to another in a
DNA sequence. Purines G or A; Pyrimidines C or T. Expect transversions to
outnumber transitions by 2:1 if mutation is fully random.
a. Transversions A<->C, C<->G, G<->T, T<->A
Vs. Transitions A<->G, C<->T
b. synonymous (keeps same amino acid) vs. nonsynonymous (changes a.a.)
1. 3rd position – about 2/3 of changes are synonymous
2. 2nd position – no synonymous changes
3. 1st position – a few synonymous changes
c. Different base substitutions will have different effects
1. synonymous – invisible or nearly invisible to natural selection, so evolve at
neutral rate
2. nonsynonymous –Effect may be small or large depending upon effect on
protein.
3. creation of a stop codon - can destroy protein function, especially if early in
protein
C. Base substitutions exhibit an excess of transitions - Do mutations occur at random?
Not quite. Look at pseudogenes (dead copies of genes, where mutations will all be
invisible to natural selection)
1. Ways to get a pseudogene (‘dead gene’)
a.
loss of function when gene function is not required. This happens in
nonphotosynthetic plants (dePamphilis’ research)
b.
more typically, from duplicate genes, where one copy may lose function
2. Study of mammalian pseudogenes – transitions about 2x more common than
transversions (contrary to our prediction, in 2a, above). Suggests bias in mutation
favoring transition.
D. Mutations change allele frequency very slowly
1. typical rates of mutation (animals and plants)
a. u = 10-9 per generation per base
b. 10–6 per generation per gene (1000 bases ave. gene)
c. 3 per person per generation (ca. 3,000,000,000 bases)
2.
the rate of evolution via mutation – build a simple model. p1 = po (1-u). If no
other forces acting, a typical rate of mutation (using 10–6 per generation per
gene) would take over 600,000 generations to shift allele frequency from p=0.1
to 0.5. Long time. Likely to be swamped by other forces.
3. how does it compare to other processes?
a. If allele is beneficial, selection will cause allele frequency to change much
much faster
b. even compared to drift, mutation is slow
E. Are mutations Beneficial? Harmful? Measuring mutation and its effect on fitness
1. balancer chromosomes allow experiments to observe effect of mutation on fitness
a. Balancer chromosomes in Drosophila– a trick to maintain deleterious mutations
in living stocks.
b. See other email (to be sent separately) with an illustrated “minitutorial” I wrote
if you’d like to know more about how balancer chromosomes work. However, if
you know the bottom line, as in “a” above, you have the key concept.
2. Mukai’s studies of the effects of mutation on fitness in flies –
a. the experiment - allow mutation in 104 lines, maintain the mutant lines in
heterozygous form by crossing with a balancer chromosome. Observed survival
of these lines through time. Rapid decline in survivorship and fitness due to
accumulation of mutations.
b. the interpretation - Mutations overall effect was to lower fitness. Recall the
watchmaker analogy. Net effect of mutation alone (natural selection to guide
evolution) would be to decrease fitness.
3. Poisson distribution of mutations – if mutations are a rare event occurring at
random, then a Poisson distribution can be used to describe the frequency of
mutations in any given chromosome (Mukai’s Drosophila) or bacterial line
(fluctuation test, below).
4. When beneficial mutations occur, do they occur because the organism needs them,
or just by chance? Are mutations adaptive?
a. The Fluctuation Test of Luria and Delbruck –
1. Design of experiments
2. Jackpot distribution vs. poisson possible results
3. Findings - jackpot distribution of resistance consistent with mutation
occurring at all times at a low level, NOT with adaptive mutations
occurring in response to organismal need.
b. Alternative views – paper on DNA mutases in bacteria and eukaryotes.
Evidence that error-prone DNA polymerases are used to replicate DNA at times
when the organisms is faced with some extreme stress. A challenge to resolve
the apparent conflict between these results and that of the Fluctuation Test.
Active area of research.
2