1. Mutation: Origin of genetic variation sources of new alleles rate and nature of mutations sources of new genes highly repeated functional sequences

2. new alleles arise from changes in DNA sequence point mutations deletions insertions transposition inversion or translocation breakpoints point mutations may either be synonymous substitutions -- no change in amino acid identity replacement substitutions -- changed amino acid frameshift mutations

3. 60-70% of mutations are transitions (vs. exp. 33%)

6. Transition Resistant

7. Basic

8. Acidic Polar

9. mutation rates vary considerably among species

10. mutation rates vary considerably among genes within a species

11. most mutations are deleterious -- C. elegans (Vassilieva et al. 2000)

12. most mutations are deleterious WHY?? If all mechanisms were nearly ‘perfect’ any change would be detrimental. Maybe Best place 50% chance of improvement

13. most mutations are deleterious WHY?? If all mechanisms were nearly ‘perfect’ any change would be detrimental. Maybe Suppose two dimensions Chance of improvement Less than 50% With many more dimensions the chance of improvement goes to zero.

14. most mutations are only slightly deleterious

16. Origins of new genes pseudogenes novel functions Repeated arrays duplications Function lost Mutations accumulate e.g. Tandem repeats of rRNA genes Absence of variation in repeats Suggests functional requirements Expression patterns Exon shuffling Internal repeats

17. New genes via internal duplications: antifreeze glycoprotein in Antarctic Toothfish (Dissostichus mawsoni) waters of the Antarctic Ocean -1.9 o C most fish freeze at -1.0 o C to –0.7 o C

18. ancestral trypsinogen gene antifreeze glycoprotein gene (from Graur & Li 2000)

19. protease kringle (plasminogen) epidermal growth factor fibronectin type-1 New genes via exon shuffling: tissue plasminogen activator evolves from four unrelated genes (from Graur & Li 2000)

20. new alleles are produced by mutation most mutations are slightly deleterious duplication is the most important mechanism for producing new genes

21. Populations are affected by two sets of processes: 1.Genetic -- mutation, recombination, independent assortment, transposition, meiotic drive 2. Ecological -- changes in population size, dispersal, mating system, environmental variation How do these processes affect population genetic variation ?

22. plumage variation in the snow goose, Chen caerulescens white phase blue phase

23. morphological variation in Panaxia dominula P. d. dominula c d c d P. d. medionigra c d c b P. d. bimacula c b c b

24. protein electrophoresis

25. PO7 275kb PO8 250kb PO3 160kb PO1 175kb Microsatellite loci for Pogonomyrmex occidentalis

26. Quantifying population genetic variation: genotype frequency = # particular genotype total number of individuals allele frequency = # particular allele total number of alleles by the law of proportions, both genotype and allele frequencies always sum to one

27. genotype A 1 A 1 A 1 A 2 A 2 A 2 number 670 200 130 genotype 670 200 130 frequency1000 10001000 geno freq. 0.67 0.20 0.13 frequency of A 1 = 0.67 + (0.20) = 0.77 1212 frequency of A 2 = 0.13 + (0.20) = 0.23 1212

28. genotype A 1 A 1 A 1 A 2 A 2 A 2 number 670 200 130 Genotype 0.67 0.20 0.13 frequency Allele frequencies: A 1 = 0.77 A 2 = 0.23 What are the expected genotype frequencies? A 1 A 1 A 1 A 2 A 2 A 2.77x.77 2x(.77x.23).23x.23.59.35.05

29. genotype A 1 A 1 A 1 A 2 A 2 A 2 Genotype G 1 G 2 G 3 frequency Allele frequency A 1 p A 2 q Expected genotype frequencies: p 2 2pq q 2 Remember: p+q = 1 Therefore (p+q) 2 = 1 2, or p 2 + 2pq + q 2 =1

30. When the observed genotype frequencies equal the expected genotype frequencies the population is said to be in Hardy-Weinberg Equilibrium

31. In the presence of certain conditions, the genotype frequencies of a population will be stable over time, and will be directly predictable from the allele frequencies. If the population is not at equilibrium, it will achieve it after one generation of random mating. Assumes: no mutation, no selection, infinite population size, no gene flow, random mating Null model for describing population genetic variation

32. How do we know whether a population is in HWE: genotypeMM MNNN number 60 20 20 obs. gen. fr. 0.6 0.2 0.2 f (M) = 0.6 + 0.1 = 0.7f (N) = 0.2 + 0.1 = 0.3 exp. gen. fr. f (M) 2 2f (M)f (N) f (N) 2 (0.7) 2 2(0.7)(0.3) (0.3) 2 0.49 0.42 0.09 49 42 9 DO NOT say: (0.7) 2 + 2(0.7)(0.3) + (0.3) 2 = 1, therefore HWE.

33. Compare observed and expected genotype distributions with a goodness of fit chi-square test with n-1 degrees of freedom (n = number of categories)     dof  =  (observed # - expected #) 2 (expected #) for the data on the previous page:    = 27.4 Look up in Table: critical values0.05.0250.010.005 df13.845.026.647.88 26.07.389.2110.6 37.829.3511.3512.84 One additional degree of freedom is lost when estimating allele frequencies dof = (n - 2)

34. HWE and sex-linked genes autosomes: half of the alleles in each sex sex chromosomes: two-thirds of the alleles in the homogametic (XX) sex if males are homogametic, A 1 A 1 A 1 A 2 A 2 A 2 A 1 / A 2 / malesfemales allele frequencies are sex-specific: p m, q m and p f, q f

35. Under random mating: q m ’ = (q m + q f ) males get an X-chromosome from each parent q f ’ = q m females get their only X-chromosome from their father 1212 p = p m + p f q = q m + q f 2323 1313 2323 1313 > > q m ’- q f ’ = ½ q m + ½ q f - q m = - ½(q m - q f )

37. genetic diversity characterizes most natural populations Hardy-Weinberg Equilibrium represents a null model for the evolution of genotype frequencies basis for mathematically examining the effects of: mutation, selection, genetic drift, gene flow, and non-random mating dynamics of HWE differ for sex-linked genes