Presentation on theme: "WHERE DOES THE VARIATION COME FROM IN THE FIRST PLACE?"— Presentation transcript:
WHERE DOES THE VARIATION COME FROM IN THE FIRST PLACE?
World’s tallest and shortest men 2 ft 5.4 in 8 ft 1 in
1) 2) 3) 4) “THE FUEL FOR EVOLUTION”
POINT MUTATIONS: ACA TTG GTA CGA CAA ACA TTT GTA CGA CAA THE DOG AND THE CAT EAT HAM THE DOT AND THE CAT EAT HAM
POINT MUTATIONS: THE DOG AND THE CAT EAT HAM THD OGA NDT HEC ATE ATH AM…. THE DOG AND THE CAT EAT HAM THT EDO GAN DTH ECA TEA THA M….
Transposable Elements: “Jumping Genes”
Chromosomal InversionsChromosomal Fusions
Translocations of Genetic Material Between Chromosomes
THE FATE OF DUPLICATE GENES Retain original function and provide additional copy of parent loci Each gene has partial role in original product Accumulate point mutation and become functionless Gain a new function through mutation and selection
GENEOME DUPLICATION: Adders-Tongue
“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!”
Rate of Mutation Gago et al Science
ORGANISMGENOME SIZEPER BASEPER GENOME Phage M x x Phage lambda 4.8 x x Phage T2, T4 1.6 x x E. coli 4.7 x x Yeast 1.4 x x Neurospora 4.2 x x Rate of Mutation Two primary questions Drake 1991
The genomic deleterious mutation rate: 0.004/cell division in E. coli 1.5/generation in D. melanogaster /generation in H. sapiens High rates in flies and humans suggest Drake’s constancy idea cannot be extended to higher organisms Constancy of Mutation Rates? Lynch 2010 Why does mutation rate increase with large genomes?
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).
THE MUTATION RATE IN HUMANS Female Cell divisions 24 (independent of age) Male Cell Divisions 36 + ((Age - 13) x 23) Age 20 Age 45 FROM: J. F. Crow Environ. Mol. Mutagenesis 21: & F. Vogel and R. Rathenberg Adv. Human Genetics
THE MUTATION RATE IN HUMANS continued… Male rate of point mutations is 4 x per base per generation The genomic mutation rate is (4 x ) x (6 x 10 9 ) bases/genome) ? More than 6% of newly fertilized eggs carry a gross chromosomal abnormality –5.5% of these terminate as spontaneous abortions FROM: J. F. Crow Environ. Mol. Mutagenesis 21: & F. Vogel and R. Rathenberg Adv. Human Genetics
Do mutations arise spontaneously OR in response to environmental stimulus??? Pattern A: Mutation is DirectedPattern B: Mutation is Random DIRECTED MUTATION
Are Mutations Random? Cairns, J., & P. L. Foster Adaptive reversion of a frameshift mutation in Escherichia coli. Genetics 128: Physiological pathway responds to selective pressure to produce mutation conferring the correct phenotype, which alleviates pressure
Mutation Rates after 10,000 Generations of Evolution Ancestral PopulationHigh Mutation Lines FROM: Sniegowski et al Nature 387: Rate of reversion from Ara - to Ara + Rate of mutation to nalidixic-acid resistance Rate of mutation to bacteriophage T5 resistance
Conclusions from Mutator Strain Experiment Most mutations deleterious, so mutator strain has negative fitness relative to wild Mutator strains are hitch-hiking in association with the important mutation Ones with high mutation rate get a beneficial mutation faster and displace wild Actually shut off DNA repair pathways to introduce many novel mutations
Recent studies by Rosenberg and Foster suggest that alteration of the pathway is essential for this result Starvation is mutagenic May have a short term advantage coping with environmental stress but over the long term they will be at a selective disadvantage. What Is Going On?
Mutational Effects: mutations of small effect are more likely the fuel for evolution by natural selection On average, what are the effects of mutation?
FROM: Lynch & Walsh 1998 On average, are mutations positive or negative?
The majority of spontaneous mutations have a slightly deleterious effect on fitness The average effect of spontaneous deleterious mutations is a 1-2% decrease in fitness (Houle et al. 1997). Conclusions from mutation accumulation studies: Why don’t we see dramatic consequences of mutations in natural populations?
SUMMARY OF KNOWLEDGE ON MUTATION RATES The spectrum of mutations is enormous The mutation rate is subject to evolutionary modification The vast majority of mutations appear to be deleterious Mildly deleterious mutations are much more common than lethals The mutation rate per generation increases with the number of cell divisions
The mutational rate of introduction of new variation is on the order of 0.1% to 1.0% of the standing variation The adaptive value of mutations changes with the ecological circumstances Mutations arise randomly with respect to their utility The mutation rate can be modified greatly by the environment SUMMARY OF KNOWLEDGE ON MUTATION RATES