1. Molecular Evolution GE3M17 Mario A. Fares

2. Nothing in biology makes sense except in the light of evolution Dobzhansky, 1973

3. Sung to the tune of "The Battle Hymn of the Republic" My bones proclaim a story of incompetent design. My back still hurts, my sinus clogs, my teeth just won’t align. If I had drawn the blueprint, I would cer-tain-ly resign. Incompetent Design! Evo-Evo-Evo-lution! Design is but a mere illusion. Darwin sparked our revolution. Science SHALL prevail! Don Wise Incompetent Design!

4. Course aims Look at evidence for evolution Discuss how to measure evolution Describe evolutionary processes

5. Fossil record Transitions Extinctions Sinosauropteryx Dromaeosaurid dinosaur

6. Nothing in biology makes sense except in the light of evolution Dobzhansky, 1973 molecular

7. actgaatg |||||||| tgacttac The molecule : DNA MALVK gene genome protein Population …. Speciation

8. Molecules versus Morphology Strictly heritable Unambiguous description Model of evolution More amenable to mathematical analysis Easier homology assessment Distant comparisons Abundant Environmental factors Classification differences Unclear models

9. DNA: Material and Markers DNA is both the raw material and the marker of evolution –Genes determine inherited differences, which is what evolution acts on –Genes change and can be used to measure evolution

10. Jean Baptiste de Lamarck Besoin - the need or desire for change in phenotype Change in phenotype Change in genotype Inherited Change in phenotype of offspring

11. August Weismann Genotype unaffected by changes in phenotype Offspring has changed genotype Change in phenotype of offspring Spontaneous and random changes in genes during reproduction Weismann distinguished somatic and germline mutation

12. Descent with modification Charles Darwin For evolution to happen, must have heredity and variation

13. Natural Selection: Survival of the Fittest “In the struggle for survival, the fittest win out at the expense of their rivals because they succeed in adapting themselves best to their environment”

14. Variation by DNA mutation Nucleotide substitution –Replication error –Chemical reaction Insertions or deletions (indels) –single base indels –Unequal crossing over

15. Consequences of point mutations within genes Figure 15-2

16. Point mutations can alter mRNA splicing

17. Measuring evolution... DNA sequences change very slowly Cannot directly observe evolution Compare two or more homologous sequences Homologous = descended from a common ancestor (= related) Analysis requires statistical models –See later “Evolution has been observed. It’s just it has not been observed while it’s happening”

18. Natural Selection: adaptive Evolution and Fitness Traps Fitness Fitness traps preclude innovation leaps

19. FITNESS (a) (b) Stable systems navigate landscapes of low complexity with smooth and densely populated adaptive picks and lowly populated deleterious valleys Non-robust systems present more complex landscapes with very dense deleterious valleys in genotypes

20. Observing Evolution of Novel Functions while it’s Happening Two stages for observing evolution: 1)Describe what we observe 2)Identify the mechanism underlying that we observe Gener. 440 Gener. 660 Gener. 1100 Gener. 1,540 Gener. 1,980 Gener. 2,200

21. Evolutionary models Neo-Darwinian (Pan-selectionist) – positive selection only Mutationist – mutation and random drift Neutralist – mutation, random drift, and negative selection

22. Positive selection A new allele (mutant) confers some increase in the fitness of the organism Selection acts to favour this allele Also called adaptive evolution NOTE : Fitness = ability to survive and reproduce

23. Advantageous allele Herbicide resistance gene in nightshade plant

24. Negative selection A new allele (mutant) confers some decrease in the fitness of the organism Selection acts to remove this allele Also called purifying selection

25. Deleterious allele Human breast cancer gene, BRCA2 Normal (wild type) allele Mutant allele (Montreal 440 Family) 4 base pair deletion Causes frameshift Stop codon 5% of breast cancer cases are familial Mutations in BRCA2 account for 20% of familial cases

26. Neutral mutations Neither advantageous nor disadvantageous Invisible to selection (no selection) Frequency subject to ‘drift’ in the population Random drift – random changes in small populations

27. Frequency of ABO Blood Group B- allele 0.4 2 13 3 9 19 18 24 20 13 12 14 8 7

29. Neo-Darwinian Model Mutation is recognised as the origin of variation Gene substitution (new allele replacing old) occurs by positive selection only Polymorphism (multiple alleles co-existing) caused by balancing selection

30. Large variation unexplained by Natural selection Zuckerkandel & Pauling – 1960s Electrophoretic gel separation of proteins Proteins travel at different speeds according biochemical properties or molecular weight 15-50% of genes have 2 or more electrophoretic alleles

31. Consequences of point mutations on gene products

32. Unexplained variation Too much polymorphism to be explained by mutation and positive selection alone (NeoDarwinian model) Why so much?

33. Neutral Theory Neutral Theory of Molecular Evolution –Motoo Kimura, 1968 Most polymorphism is selectively neutral Majority of evolutionary changes caused by random genetic drift of selectively neutral (or almost neutral) alleles Still allows for some selection Motoo Kimura (1924-94)

34. Genetic Drift

35. Random Genetic Drift Selection Allele frequency 0 100 advantageous disadvantageous

36. Genetic Drift Each new allele (mutant) has a chance of being fixed (= present in all individuals) in the population Probability is proportional to frequency Selection (positive or negative) also affects rate and likelihood Neutral alleles have no selection May ‘drift’ to fixation or extinction Under genetic drift the probability of fixation is simply equal to freq.

37. Rate of Neutral Evolution  = neutral mutation rate per allele Neutral mutation New allele Frequency of 1/2N Population of N diploid individuals Containing 2N alleles (2 per individual) Probability of being fixed 2N  = number of new mutations in a population of N Mutation Rate Rate of neutral evolution = rate of mutation X probability of mutation being fixed = 2N  X 1/2N =  Under the neutral theory, the rate of substitution = rate of mutation

38. Molecular clock

39. But … Molecular clock does not always hold Still is a useful concept … more details later …