1. Evolution, Adaptation, Natural Selection and Fitness Dr Pupak Derakhshandeh, PhD Assiss. Prof. of Medical Science of Tehran University

2. 2 The Process of Natural Selection Evolution Reproductive Ability + Environmental Restrictions Reproductive Ability + Environmental Restrictions Struggle for Existence + Heritable Variations Struggle for Existence + Heritable Variations Natural Selection + Environmental Changes Natural Selection + Environmental Changes

3. 3 Model of Selection Heritable variation Selection Other Evolutionary Forces

4. 4 Four evolutionary forces Mutation Drift Isolation Natural selection Non overlapping generation *

5. 5 Evolutionary Forces Mutation –New allele arises by physical change in structure of DNA Genetic drift –Random drift in allele frequency by chance, important mainly in small populations Isolation –Isolated populations can diverge due to drift or natural selection Natural selection –The process of differential (survival and reproduction of individuals)

6. 6 Natural selection The only force that produces adaptations “ The only force that produces adaptations ” Conditions for evolution by natural selection : Variation Heritability ( h 2 ) Differential fitness

7. 7 Genotypic LevelPhenotypic Level Genetic variability exists (alternative alleles exist) Phenotypic variation (genetic variation is expressed) Some variation survive and reproduce more successfully in given environment Phenotypic variation passes to offspring (h 2 ≠ 0) Distribution of Allele Frequencies will Change Through Time (Adaptive Evolution)

8. 8 Important to recognize 1.Selection and response: Natural selection is the process of differential survival and reproduction by different individuals in a specific environment Selection acts on the phenotype

9. 9 1.Selection and Response: Response to selection is different in allele frequencies, if phenotypic variation is heritable, i.e. due to genetic variation. Evolution occurs at level of genotype. Evolution IS simply change in allele frequency Important to recognize

10. 10 2. Selection is caused by all aspects of the environment (Biotic and Abiotic) >Therefore adaptation is relative to a given context >An individual’s fitness is relative to its environment Important to recognize

11. 11 3. Whether an allele increases or decreases in frequency: –depends on what alternative alleles exist in the population –Fitness is relative to alternative genotypes (phenotypes) Important to recognize

12. 12 4. Heritability: proportion of variation in phenotype that is due to genotype h 2 =  2 g /  2 p Important to recognize

13. 13 Heritability Two identical genotypes, in different environments, may not produce identical phenotype. Two different genotypes, in the same environment, can produce similar or identical phenotype.

14. 14 Heritability the phenotype is product of interaction between genotype and environment. Heritability measures what proportion of variation in the phenotype is due to the genotype. There are many ways to estimate heritability. Most common is: –Offspring-parent regression heritability

15. 15 Offspring-parent regression heritability Value of trait In offspring Value of trait in father

16. 16 Measuring Natural Selection 1. Fitness is the currency of natural selection –Absolute fitness = W –Probability of survival X reproductive output Relative fitness = ω Absolute fitness of a phenotype Absolute fitness of “most fit” phenotype –Selection coefficient = s = 1 - ω –A measure of the strength or intensity of selection against a phenotype

17. 17 Relative Fitness Consider a population of newborns with variable survival among three genotypes: ω = Relative Fitness ω= 1 for best performer; others are ratios relative to best performer: A1A1A1A1 A1A2A1A2 A2A2A2A2 N100 Survival805640 ω 11 = 80/80 = 1ω 12 = 56/80 = 0.7ω 22 = 40/80 = 0.5

18. 18 Average Fitness ω Use genotype frequencies to calculate weighted fitness for entire population ω = P(ω 11 ) + H(ω 12 ) + Q(ω 22 ) ω = (150/300) 2 (1) + (0.5)(0.7) + (150/300) 2 (0.5) = 0.93 When fitness varies among genotypes, average fitness of the population is less than 1 GenotypeA1A1A1A1 A1A2A1A2 A2A2 A2A2 ω10.70.5

19. 19 Selection Against the Homozygous Recessive Phenotype selection that is directed only against the homozygous recessive phenotype (one of the most common patterns of selection ! )

20. 20 Selection Against One of The Homozygotes the recessive allele (a) will not completely disappear it is still passed on by heterozygous (Aa) parents to the half of their children

21. 21 Selection Against One of The Homozygotes Total population fitness W GenotypeAAAaaa Fitness1.0 0.2 Total fn p AA w AA + p Aa w Aa + p aa w aa W Allelic fn (A)(p AA w AA + 1/2 p Aa w Aa )wAwA Allelic fn (a)(1/2 p Aa w Aa + p aa w aa )wawa Genotype frequency (A) (p AA w AA + 1/2 p Aa w Aa )/Wp AA Genotype frequency (a) (1/2 p Aa w Aa + p aa w aa )/Wp aa

22. 22 Selection Against One of The Homozygotes the allele fitnesses will change –if the allele frequencies change! a rare detrimental/lethal allele, as recessive has very little fitness –if it is lethal in the homozygote because when it is very rare, it is almost never in homozygotes Note:

23. 23 Selection Against One of The Homozygotes A population fitness less than 1 does not mean a dead population just a population that is not reaching its maximum possible fitness the fitness of the heterozygote is represented by a multiplier h

24. 24 Selection Against One of The Homozygotes h=0,  Aa =1 h=1,  Aa =1 When A > a GenotypeAAAaaa Fitness1.01 – h s1 - s When a > A GenotypeAAAaaa Fitness1 - S1 (h)1

25. 25 Selection Against One of The Homozygotes The multiplier h: – a measure of dominance (a). –h=1 means that (a) is dominant:       –h=0 means that (a) is recessive and (A) is dominant       –h=0.5 means that it is perfectly additive

26. 26 Directional / Purifying selection Additive or Co-dominant (h=1/2) s = 0.5, h = 0.5 In this case p a will drop smoothly toward 0. GenotypeAAAaaa Fitness1.01 – h s1 - s Fitness1.01 – ½ s1 - s Fitness1.00.750.5

27. 27 Directional / Purifying selection Natural selection favors a single phenotype Allele frequency continuously shifts in one direction the advantageous allele will increase in frequency independently of its dominance relative to other alleles (i.e. even if the advantageous allele is recessive, it will eventually become (fixed)

28. 28 Directional selection

29. 29 Directional / Balancing selection Selection may favor multiple alleles It is the same as purifying selection Removes deleterious mutations from a population (-) Directional selection is a particular mode or mechanism of natural selection

30. 30 Directional selection 1.At first, the light-gray form of the peppered moths on light-gray tree 2.industrial pollution: darkened the tree trunks 3.notice by bird 4.the numbers of dark-gray moths increased 5.In recent years pollution controls have led to decreased amounts of soot on the trees 6.the light colored moths are increasing in numbers ! Example :

31. 31 Directional selection 12 3

32. 32 Selection Against One of The Homo/Heterozygotes (Directional selection) Albinism (AA/Aa) Diabetes (AA/Aa) HIV / bubonic Plague (Aa): –CCR5-delta 32

33. 33 Selection Against Both Homozygotes Complete selection against both homozygotes (AA and aa)

34. 34 Selection Against Both Homozygotes Nature selecting against both homozygotes was found in Central Africa 10% of the world's human population: –infected by malaria –90% of the cases are in Sub-Saharan

35. 35 Selection Against The Heterozygote And One Of The Homozygotes For example, if just aa genotype individuals fail to reproduce Only AA people will contribute their genes to the next generation Genetic testing and counseling: –Discouraging heterozygous carriers ( Aa) of harmful recessive alleles (aa) from reproducing –Sickle-cell trait and Tay-Sachs disease

36. 36 Balancing Selection / Overdominance / Heterozygote Advantage GenotypeAAAaaa Fitness0.91.00.2

37. 37 Balancing Selection / Overdominance / Heterozygote Advantage (Aa) or Selection Against both of The Homozygotes

38. 38 Selection Against both of The Homozygotes ( ≠ Distruptive selection ) The multiplier h: – A measure of dominance (A/a). – h<0 means that (A/a) is dominant:       Or      

39. 39 Directional selection

40. 40 Overdominance ! Genotype AA Aa aa fitness1.0 1-hs 1-s H<0 means: 1-(-1/2)s=1+1/2s (0<s<1) 1.5  <1

41. 41 Genotype AA Aa aa fitness 0.9 1.0 0.2 In this case p A will approach a value that maximizes W Both A and a will persist in the population The equilibrium point depends on w AA and w aa ( in this case, it's p A=0.89, p a=0.11 Examples: Sickle-cell anemia

42. 42 Disruptive Selection / Underdominance / Heterozygote Disadvantage GenotypeAAAaaa Fitness1.00.81.0 H>1 means that (A or a) is dominant:       Or      

43. 43 Disruptive Selection h >1 means: 1-(1.5)s = 1-1/2s (0<s<1) -1/2 <w<1 GenotypeAAAaaa Fitness1.01 – h s1.0

44. 44 Selection Against The Heterozygote Half will normally be homozygous dominant (AA) and half will be homozygous recessive (aa)

45. 45 Selection Against All Genotypes Completely selects against all genotypes (AA, Aa, aa) All genotypes are at a selective disadvantage

46. 46 Genetic Change Between Generations GenotypeAAAaaa Initial freq.p 2p 2 2pqq 2q 2 Rel. Fitnessw AA w Aa w aa Freq. After selection p 2 w AA 2pq w Aa q 2 w aa Rel. freq. after sel. p 2 w AA w 2pq w Aa w q 2 w aa w

47. 47 Selection Against a Recessive GenotypeAAAaaa Initial freq.p 2p 2 2pqq 2q 2 Rel. Fitness111 - s Freq. After selection p 2p 2 2pqq 2 - sq 2 Rel. freq. after sel. p 2wp 2w 2pq w q 2 - sq 2 w

48. 48 Relative Fitness GenotypeA 1 A 1 A 2 A 2 Total a405010100 b809010180 b / a80/4090/5010/10- Rel. reproductive fitness 2/21.8/21/2

49. 49 Relative Fitness:Survival (Tay Sach) GenotypeA1A1A1A1 A1A2A1A2 A2A2A2A2 Survival fit.10.90.5 Fertility fit.111 Net fit.1x1 = 11x0.9 = 0.91x0.5 = 0.5

50. 50 Relative Fitness:Fertility (CF) GenotypeA1A1A1A1 A1A2A1A2 A2A2A2A2 Survival fit.111 Fertility fit.10.90.5 Net fit.1x1 = 11x0.9 = 0.91x0.5 = 0.5

51. 51 Modeling directional selection: allele frequency change is determined by relative fitness GenotypeA1A1A1A1 A1A2A1A2 A2A2A2A2 ViabilityW 11 W 12 W 22 Rel. viability1W 12 / W 11 W 22 / W 11 Relative11 - hs1 - s Where 1 – hs = W 12 / W 11 and 1 – s W 22 / W 11 The parameter s is called the selection coefficient and the parameter h is called the heterozygotous effect. h = 0A 1 is dominant, A 2 recessive h = 1A 2 is dominant, A 1 recessive 1 < h < 1Incomplete dominance h < 0Overdominance h > 1Underdominance

52. 52

53. 53 Selection against a dominant phenotype

54. 54 Selection favoring the heterozygote

55. 55 Simple models of selection relative fitness of A 1 A 1 1.0 0.5 0.0 0.5 1.0 w 11 > w 12 > w 22 fix A 1 w 11 > w 12 < w 22 unstable polymorphism w 11 w 22 stable polymorphism w 11 < w 12 < w 22 fix A 2 relative fitness of A 2 A 2

56. 56  q= q’ - q = - q =  q= q(1-sq) 1-sq 2 q – sq 2 – q + sq 3 1-sq 2 -sq 2 (1 – q) 1-sq 2 How much has the frequency of A 2 Change after one generation of selection ?

57. 57 (Roughgarden 1979) change in the frequency of a deleterious recessive 2

58. 58 selection against a deleterious recessive allele qq q

59. 59 change in the frequency of a deleterious dominant (Roughgarden 1979)

60. 60 Selection against a dominant allele qq q

61. 61 Selection favoring heterozygotes GenotypeA1A1A1A1 A1A2A1A2 A2A2A2A2 Initial genotype freq. P2P2 2pq q 2 Rel. fitness1 - s11 - t w = p 2 (1 - s) + 2pq(1) + q 2 (1 - t) = 1 - p 2 s - q 2 t Genotype freq. after selection p 2 (1 - s) 1- p 2 s - q 2 t 2pq(1) 1- p 2 s - q 2 t q 2 (1+t) 1- p 2 s - q 2 t s and t = two different fitnesses !

62. 62 heterozygote advantage qq q

63. 63 GenotypeA1A1A1A1 A1A2A1A2 A2A2A2A2 Initial genotype freq. P2P2 2pq q 2 Rel. fitness1+s11+t w = p 2 (1+s) + 2pq(1) + q 2 (1+t) = 1 + p 2 s + q 2 t Genotype freq. after selection p 2 (1+s) 1+p 2 s+q 2 t 2pq(1) 1+p 2 s+q 2 t q 2 (1+t) 1+p 2 s+q 2 t Selection against heterozygotes