1. WHERE DOES THE VARIATION COME FROM IN THE FIRST PLACE?

2. World’s tallest and shortest men
8 ft 1 in
World’s tallest and shortest men
2 ft 5.4 in

3. “THE FUEL FOR EVOLUTION”1) 2) 3) 4)

4. ACA TTG GTA CGA CAA ACA TTT GTA CGA CAA THE DOG AND THE CAT EAT HAM
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

5. THE DOG 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….

6. Transposable Elements:
“Jumping Genes”
Transposable element actually codes for a reverse transcriptase enzyme that copies itself back into a new position
Very similar to HIV or retroviruses

7. Chromosomal Inversions
Chromosomal Fusions

8. Translocations of Genetic Material Between Chromosomes

9. GENE DUPLICATION:

10. 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

11. GENEOME DUPLICATION:
Adders-Tongue

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!”

13. Rate of Mutation
Gago et al Science

14. Rate of Mutation Two primary questions
ORGANISM GENOME SIZE PER BASE PER GENOME
Phage M x x
Phage lambda x x
Phage T2, T x x
E. coli x x
Yeast x x
Neurospora x x
Drake 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. sapiens
High rates in flies and humans suggest Drake’s constancy idea cannot be extended to higher organisms
Why 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 45
FROM: 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 generation
The 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 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

20. DIRECTED MUTATION
Do mutations arise spontaneously OR in response to environmental stimulus???
Pattern A: Mutation is Directed
Pattern B: Mutation is Random

21. Are Mutations Random?
Physiological pathway responds to selective pressure to produce mutation conferring the correct phenotype, which alleviates pressure
Cairns, 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 Evolution
Ancestral Population High Mutation Lines
Rate of reversion from Ara- to Ara+
Rate of mutation to nalidixic-acid resistance
Rate of mutation to bacteriophage T5 resistance
FROM: Sniegowski et al Nature 387:

23. 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

24. What Is Going On?
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.

25. On average, what are the effects of mutation?
Mutational Effects: mutations of small effect are more likely the fuel for evolution by natural selection
Had very poor eyesight and learned to visualize math problems in head
Before computers so employed hundreds of people to crunch equations
Published the genetical theory of natural selection – important book for the modern synthesis
Major 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 slightly
deleterious effect on fitness
The average effect of spontaneous deleterious mutations is
a 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 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

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 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