10 THE FATE OF DUPLICATE GENES Retain original function and provide additional copy of parent lociEach gene has partial role in original productAccumulate point mutation and become functionlessGain a new function through mutation and selection
12 “It’s like someone has taken the encyclopaedias, ripped out all the individual pages, torn some of them, photocopied everything dozens of times, and stuffed the whole lot in a gigantic messy drawer….& It’s like every page in its messy drawer is hard-bound!”
14 Rate of Mutation Two primary questions ORGANISM GENOME SIZE PER BASE PER GENOMEPhage M x xPhage lambda x xPhage T2, T x xE. coli x xYeast x xNeurospora x xDrake 1991
15 Why does mutation rate increase with large genomes? Constancy of Mutation Rates?The genomic deleterious mutation rate: 0.004/cell division in E. coli 1.5/generation in D. melanogaster /generation in H. sapiensHigh rates in flies and humans suggest Drake’s constancy idea cannot be extended to higher organismsWhy does mutation rate increase with large genomes?Lynch 2010
16 In the 1930s, the pioneering geneticist J. B. S In the 1930s, the pioneering geneticist J. B. S. Haldane noticed a peculiar inheritance pattern in families with long histories of haemophilia. The faulty mutation responsible for the blood-clotting disorder tended to arise on the X chromosomes that fathers passed to their daughters, rather than on those that mothers passed down. Haldane subsequently proposed that children inherit more mutations from their fathers than their mothers, although he acknowledged that “it is difficult to see how this could be proved or disproved for many years to come”.Haldane, J. B. S. Ann. Eugen. 13, 262–271 (1947).
17 THE MUTATION RATE IN HUMANS Female Cell divisions 24 (independent of age)Male Cell Divisions 36 + ((Age - 13) x 23) Age 20 Age 45FROM: J. F. Crow Environ. Mol. Mutagenesis 21: & F. Vogel and R. Rathenberg Adv. Human Genetics
18 THE MUTATION RATE IN HUMANS continued… Male rate of point mutations is x 10-8 per base per generationThe genomic mutation rate is (4 x 10-8) x (6 x 109) bases/genome) ?More than 6% of newly fertilized eggs carry a gross chromosomal abnormality5.5% of these terminate as spontaneous abortionsFROM: J. F. Crow Environ. Mol. Mutagenesis 21: & F. Vogel and R. Rathenberg Adv. Human Genetics
20 DIRECTED MUTATIONDo mutations arise spontaneously OR in response to environmental stimulus???Pattern A: Mutation is DirectedPattern B: Mutation is Random
21 Are Mutations Random?Physiological pathway responds to selective pressure to produce mutation conferring the correct phenotype, which alleviates pressureCairns, J., & P. L. Foster Adaptive reversion of a frameshift mutation in Escherichia coli. Genetics 128:
22 Ancestral Population High Mutation Lines Mutation Rates after 10,000 Generations of EvolutionAncestral Population High Mutation LinesRate of reversion from Ara- to Ara+Rate of mutation to nalidixic-acid resistanceRate of mutation to bacteriophage T5 resistanceFROM: Sniegowski et al Nature 387:
23 Conclusions from Mutator Strain Experiment Most mutations deleterious, so mutator strain has negative fitness relative to wildMutator strains are hitch-hiking in association with the important mutationOnes with high mutation rate get a beneficial mutation faster and displace wildActually shut off DNA repair pathways to introduce many novel mutations
24 What Is Going On?Recent studies by Rosenberg and Foster suggest that alteration of the pathway is essential for this resultStarvation is mutagenicMay have a short term advantage coping with environmental stress but over the long term they will be at a selective disadvantage.
25 On average, what are the effects of mutation? Mutational Effects: mutations of small effect are more likely the fuel for evolution by natural selectionHad very poor eyesight and learned to visualize math problems in headBefore computers so employed hundreds of people to crunch equationsPublished the genetical theory of natural selection – important book for the modern synthesisMajor advances in statistics – correlation, ANOVA, founder of population genetics
26 On average, are mutations positive or negative? FROM: Lynch & Walsh 1998
27 Conclusions from mutation accumulation studies: The majority of spontaneous mutations have a slightlydeleterious effect on fitnessThe average effect of spontaneous deleterious mutations isa 1-2% decrease in fitness (Houle et al. 1997).Why don’t we see dramatic consequences of mutations in natural populations?
28 SUMMARY OF KNOWLEDGE ON MUTATION RATES The spectrum of mutations is enormousThe mutation rate is subject to evolutionary modificationThe vast majority of mutations appear to be deleteriousMildly deleterious mutations are much more common than lethalsThe mutation rate per generation increases with the number of cell divisions
29 SUMMARY OF KNOWLEDGE ON MUTATION RATES The mutational rate of introduction of new variation is on the order of 0.1% to 1.0% of the standing variationThe adaptive value of mutations changes with the ecological circumstancesMutations arise randomly with respect to their utilityThe mutation rate can be modified greatly by the environment