Natural Selection

1. NaturalSelection

2. Natural Selection An Adaptive Mechanism

3. Evolutionary Mechanisms Genetic Drift Migration Mutations Natural Selection Non-adaptive Adaptive

4. Darwin Evolution acts through changes in allele frequencyat each generation According to Darwin, this happens via Natural Selection (He considered Selection only, and not other evolutionary mechanisms, such as mutations, genetic drift, etc.)

5. Sources of Genetic Variation Mutation generates genetic variation Epigenetic modification changes expression of genes Genetic Drift can reduce genetic variation Natural Selection Natural Selection acts on genetic or epigenetic variation in a population Without genetic or epigenetic variation, Natural Selection cannot occur

6. OUTLINE (1) General Description of Natural Selection (2) Modes of Natural Selection (3) Selection Violating Hardy-Weinberg Equilibrium

7. Darwin’s contribution: Population Speciation as a result of Natural Selection • Too many offspring produced • Limited resources and competition • Variation in a population • Better adapted individuals survive • Survivors leave more offspring • Thus, average character of population is altered

8. Natural Selection The differential survival and/or reproduction of classes of entities that differ in one or more characteristics The only evolutionary force that is ADAPTIVE NOT random, but deterministic

9. Darwin • Population speciation

10. Darwin • Population speciation mutation

11. Darwin • Population speciation Selection favors

12. Darwin • Populationspeciation Greater Fitness

13. AZT Selection on pathogens imposed by Drugs (refer to Lecture 1) • AZT (Azidothymidine) is a thymidine mimic which stops reverse transcription • Mutations in the reverse transcriptase gene of HIV arises such that the enzyme can recognize AZT • The drugs impose Selection on the virus. Genetic variation (generated by mutations) allows the virus to respond to selection and evolve drug resistance

14. Selection imposed by Transmission Rate on Virulence of HIV • Need to keep host alive long enough to get passed on to the next host (Tradeoff between fast population growth and keeping the host alive) • High Transmission rate : High Virulence (Can grow fast and jump to the next host; ok if host dies; genetic strain that grows faster will win) • Low Transmission Rate : Low Virulence (More virulent strains would die with the host and get selected out; less virulent strain will win)

15. High Transmission Rate If the virus is likely to move to a new host the faster growing (and more virulent) strain is likely to overtake the slower strains and “win” It’s ok to kill the host, since the chances of jumping to a new host is high Natural selection will favor the more virulent strain

16. Low Transmission Rate If the virus is not likely to move to a new host the slower growing (and less virulent) strain is likely to “win” It’s not ok to kill the host, since the chances of jumping to a new host is low. If the virus kills the host, it will kill itself Natural selection will favor the less virulent strain

17. Evolution of HIV resistance in Human Populations CCR5-Δ32 (or CCR5-D32 or CCR5 delta 32) is a mutant allele of the receptor CCR5, where the deletion of a 32 base pair segment makes the receptor nonfunctional The allele has a negative effect upon T cell function, but appears to protect against smallpox and HIV HIV has no receptor to bind to and cannot enter the cell This allele is found in 14% of Europeans HIV can impose selective pressure for CCR5-Δ32, increasing the frequency of this allele in human populations (Sullivan et al. 2001) Amy D. Sullivan et al. 2001. The coreceptor mutation CCR5Δ32 influences the dynamics of HIV epidemics and is selected for by HIV. Proc Natl Acad Sci USA. 98: 10214–10219.

18. Frequency shift in CCR5- D32 allele Fr

19. Modes of Selection

20. Selection on discrete vs continuous characters • When phenotypes fall into discrete classes (like Mendel’s yellow vs green peas), we can think of selection acting directly on genotypes • Such discrete traits are usually coded by one or a few genes (loci) • However, when phenotypes fall into a continuum (continuous traits such as those Darwin examined, beak shape, body size), you will see changes in the distributions of traits (next slide)–such traits are called “quantitative traits,” coded by many loci

21. DIFFERENT MODES OF SELECTION(Herron & Freeman Section 9.6)

22. Directional Selection on a discrete trait Directional Selection on a continuous trait Directional Selection: Selection changes frequency of alleles in one direction die shift in distribution

23. Directional Selection on a discrete trait Directional Selection: Selection changes frequency of alleles in one direction Mock Example Directional Selection on a discrete trait AA Aa aa Generation 1 0.80 0.15 0.05 Generation 2 0.60 0.30 0.10 . . . . . . . . . . . . Generation X 0.04 0.16 0.75

24. Directional Selection on a discrete trait • How will selection act if A is dominant and selection favors red? AA Aaaa • How will selection act if A is not dominant, but Aa intermediate? AAAaaa • Under which situation will the “a” allele be preserved in the population longer?

25. How will selection act if A is dominant and selection favors red? AA Aaaa Selection will act on AA and Aa in the same manner • How will selection act if A is not dominant, but Aa intermediate? AAAaaa Selection will act more strongly on AA • Under which situation will the “a” allele be preserved in the population longer? • The first above, as the “a” allele is more effectively masked in the heterozygote state Directional Selection on a discrete trait

26. Selection on Dominant vs Recessive Alleles • Herron & Freeman • Selection against recessive allele Set fitness of genotypes to: WAA = 1, WAa = 1, Waa = 1 – s (s = selection coefficient) • Selection against dominant allele Set fitness of genotypes to: WAA = 1 - s, WAa = 1 - s, Waa = 1 (AA and Aa have same phenotype)

27. Selection on Dominant vs Recessive Alleles • What Happens? • Selection against recessive allele In Allele A1, set fitness of genotypes to: WAA = 1, WAa = 1, Waa = 1 – s (s = selection coefficient) • Selection against dominant allele Set fitness of genotypes to: WAA = 1 - s, WAa = 1 - s, Waa = 1 (AA and Aa have same phenotype)

28. Selection on Dominant vs Recessive Alleles • Selection against recessive allele: • As recessive allele becomes rare, rate of its disappearance slows down • As homozygote recessive allele becomes rare, most are in the heterozygous state and are masked from selection • Selection against dominant allele: • Dominant allele that is disfavored by selection is removed quickly from the population

29. Directional Selection: Selection changes frequency of alleles in one direction • Genetic diversity is reduced • (knock out maladapted genotypes) • Examples: • Drug-resistance in tuberculosis and HIV • Agriculture: artificial selection for specific traits • Sexual selection for a trait (e.g. for bright plumage)

30. Directional Selection

31. Directional Selection during Domestication • Rapid evolution under intense directional selection for large and numerous kernals • Selection by humans for a few regulatory genes (affecting transcription) • Reduced genetic diversity in domesticated corn

32. Morphological differences between teosinte and maize • Maize with tb1 knocked out • Has branching patterns like teosinte teosinte maize

33. Genes selected for in Corn Corn Major morphological differences are due to directional selection on 5 genesGenes: • Teosinte branched1 (tb1): single mutation affects branching and inflorescence• Regulator of tb1• tgaglume (outer coating) reduction on chromosome X• teosinte – ~8-12 kernels F1 hybrid 8 rows, corn 20+rowsEvidence for selection in 2-4% of genes, ~1200 genes F1 Hybrid Teosinte

34. Hardy Weinberg revisited AA Aaaa Generation 1 250 500 250 Generation 2 750 200 50 Generation 3 900 90 10 (1) Is this population remaining in HW Equilibrium from generation to generation? (2) What might be going on?

35. Hardy Weinberg revisited AA Aaaa Generation 1 250 500 250 Generation 2 750 200 50 Generation 3 900 90 10 (1) Is this population remaining in HW Equilibrium from generation to generation? ***check if (a) alleles frequencies change across generations and (b) whether the allele frequencies do not yield the predicted genotype frequencies (2) What might be going on?

36. AA Aaaa Generation 1 250 (freq = 250/1000) 500 250 Generation 2 750 (freq = 750/1000) 200 50 Generation 3 900 (freq = 900/1000) 90 10 First convert # of individuals to frequency of genotypes (1) Is this population remaining in HW Equilibrium from generation to generation? NO Gen1 Freq of A (p) = 0.25 + (0.50/2) = 0.50 Freq of a (q) should be = 1 -0.50 = 0.50 Gen2Freq of A (p) = 0.75 + (0.20/2) = 0.85 Freq of a (q) = 1-0.85 = 0.05 + (0.20/2) = 0.15 Gen3 - can do same calculations **Allele and genotype frequencies are changing across generations: freq of A is increasing across the 3 generations **Genotype frequencies deviated from expectations based on allele frequencies: freq of A is 0.5 in Gen1, so expect AA =0.25 at Gen2, (2) What might be going on? Directional selection favoring A?

37. Hardy Weinberg revisited AA Aaaa 0.44 0.56 0 (1) Is this population in HW Equilibrium? (2) Are the HW expectations the same as the genotype frequencies above? Hint: Calculate the genotype frequencies from the # above, and then calculate allele frequencies. Use the allele frequencies to calculate HW expectations. (3) What might be going on?

38. Hardy Weinberg revisited AA Aaaa 0.40 0.60 0 (1) Is this population in HW Equilibrium? NO (2) Are the HW expectations the same as the genotype frequencies above?NO Freq of A (p) = 0.40 + (0.60/2) = 0.70 Freq of a (q) should be = 1 - 0.70 = 0.30 Based on HW expectations, freq of aa should = 0.3 x 0.3 = 0.09 aa is missing! Negative selection acting against aa? aa might be a homozygous recessive lethal

39. Stabilizing Selection (on discrete or continuous traits) • Selection acts against the extremes (favors intermediate trait) =purifying selection • The average trait value stays the same • Genetic diversity is reduced • This is going on all the time, as deleterious alleles are getting selected out of the population • Examples: • Selection against new harmful mutations • Selection for an optimal number of fingers Selection for optimal body size die

40. Example of Stabilizing Selection Selection for an optimal number of eggs

41. Disruptive Selection (on discrete or continuous traits) • Selection favors the extremes • Genetic diversity is increased (help maintain genetic variation; knock out alleles that code for intermediate traits) • Can lead to formation of new species • Examples: • Niche Partitioning (Specialization on different resources, food) • Differences in habitat use • Will discuss more in lecture on Speciation • Sexual selection for different traits (blue birds mate with blue, red birds mate with red)—intermediate colors selected against

42. Disruptive Selection

43. Balancing Selection(on discrete or continuous traits) • Balancing Selectionis a generic term to refer to any type of selection that acts to maintain genetic variation in a population • There are different mechanisms: Fluctuating selection, selection favoring heterozygote (=overdominance) • Examples: • Selection for heterozygotes (sickle cell anemia, and cystic fibrosis) • Selection for different traits in different environments • Selection for different traits at different times (fluctuating selection)

44. Balancing Selection • An Example of one mechanism: • Overdominance: Selection favoring the heterozygote AA Aa aa Generation 1 0.25 0.50 0.25 Generation 2 0.20 0.60 0.20 Generation 3 0.10 0.80 0.10 • Genetic diversity is maintained in a population in this case because the heterozygote maintains both alleles • Example: Sickle Cell anemia

45. Balancing Selection • An Example of one mechanism: • Overdominance: Selection favoring the heterozygote AA Aa aa Generation 1 0.25 0.50 0.25 Generation 2 0.20 0.60 0.20 Generation 3 0.10 0.80 0.10 • In this case, allele frequencies (of A and a) do not change. However, the population did go out of HW equilibrium because you can no longer predict genotypic frequencies from allele frequencies • For example, p = 0.5, p2 = 0.25, but in Generation 3, the observe p2 = 0.10

46. Balancing Selection • An Example of one mechanism: • Overdominance: Selection favoring the heterozygote AA Aaaa Generation 1 0.25 0.50 0.25 Generation 2 0.20 0.60 0.20 Generation 3 0.10 0.80 0.10 • Genetic diversity is maintained in a population in this case because the heterozygote maintains both alleles • Example: Sickle Cell anemia

47. Balancing Selection • An Example of one mechanism: • Overdominance: Selection favoring the heterozygote AA Aaaa Generation 1 0.25 0.50 0.25 Generation 2 0.20 0.60 0.20 Generation 3 0.10 0.80 0.10 • Why is this NOT stabilizing selection? In Stabilizing Selection genetic diversity decreases as the population stabilizes on a particular trait value (a quantitative trait, like body size, height, intermediate color –of a multilocus nature)

48. Sickle cell anemiaexample of balancing selection • Reduced ability of red blood cells to carry oxygen (mutation in HbS gene, makes defective hemoglobin protein) • HAHA: homozygous, no effects of disease (sickle cell anemia) • HAHs: heterozygotes, suffer mild effects • HsHs: homozygous, usually die before reproduction

50. Sickle cell anemia • When Malaria is present HAHs advantage: red blood cells with abnormal hemoglobin tend to sickle when infected by parasite and are culled out 72% HAHA; 25% HAHs; and 2.2% HsHs(die young) • Malaria not present AA advantage 99.999% HAHA; 0.001% HAHs; and 0% HsHs • With malaria, balancing selectionfor the heterozygote • Without malaria,directional selectionfor HAHA