What outcomes do which base sequence changes have?
- Synonymous- none
- Transition/transversion- changes aa
- Frame-shift
- Stop
Give and example of a point mutation
Haemoglobin- change from A to T in coding strand of β-globin protein
- substitutes valine for glutamic acid
- heterozygotes resistant to malaria
- homozygotes sickle cell anaemia
What are the possible consequences of mutation?
• Loss of function
- typically recessive
- eg. Drosophila white eye
• Gain of function (not benefit)
- typically dominant
- eg. Drosophila antennapedia
• Conditional
- mutational effect varies with environment
- eg. Temperature
• Lethal- kills bearer
Outline a mutation accumulation study
(Mukai, 1972)
• Examined mutations of second chromosomes of ~1.7 million flies using balanced chromosomes
• Made 101 chromosomal lines using balancers. Each carried independently extracted wild type second chromosome from founding single males
• To maintain experimental line:
- Cross heterozygotes in each gen to reference balancer stock and picked out heterozygotes from progeny
- Repeated for 60 generations
• Reasons for design:
- Many gens allows mutations to arise and trapped on wt chromosome
- mutations sheltered from selection (unless dominant)
• Assay of fitness of experimental lines- measure of mutation accumulation
- At intervals tested net effect on fitness of wt chromosomes
- Male homozygous to measure viability- cross heterozygotes together and score proportions of progeny genotypes- expected 2:1 cw to wt
- drop in proportion of wt means drop in fitness (measured by viability)
15% reduction at 40 gens
50% reduction at 60 gens
-> net effect of new mutations is to reduce fitness
What are balancer chromosomes?
- Contain multiple overlapping inversions which prevent recombination
- Marked with mutant dominant alleles that alter appearance of bearer (curly wing on c2 balancer)
- Dominant markers are lethal in homozygous condition
- Can cross population of interest and balancer stock to extract specific chromosomes from test pop
- Individuals heterozygote for balancer don’t produce recombinant progeny and can be readily identified
What are the problems with Mukai’s design?
Rests on notion that balancer chromosomes are reference genotype of standard fitness
Is mutation under genetic control?
Yes. Transposable elements TEs: short DNA sequences with capacity to move around genome inserting copies into recipient sites and leaving donor copy in place
• Varied effects- can affect function of genes at or near transposition sites
- TEs May contain terminator signals and stop codons-> insertion prevents full transcription and translation
- May contain promoter and splicing signals-> change transcription levels
What are P elements and give an example
Cause hybrid dysgenesis in crosses between strains of fruit flies
• P elements encode transposase needed for movement of TEs
• Also encode repressor of transposition- accumulates in cytoplasm of developing cells
• M strains lack element and repressor
- P/M males * P females -> no effect on mutation rate as female cytoplasm contains repressor
- P males * M females -> elevated mutation rate, F1 low fitness, often sterile; female cytoplasm lacks repressor
Is evolution ever limited by availability of new mutations? Give an example
Yes.
• Evidence from AS applied to selection on bristle phenotype of Drosophila
• Compared populations of fly descended from dysgenic cross between P strains with control strain descended from non-dysgenic population
• In selected strains founded from dysgenic cross there is a steeper direct response to selection because:
- elevates mutation rate means more genetic variation for AS to work with
-> evolution constrained by supply of new mutations
