Evolution Lectures 9,10,11: Population Genetics: Mutation, Migration and Drift (Chapter 7)

1. Evolution Lectures 9,10,11: Population Genetics: Mutation, Migration and Drift(Chapter 7)

2. Mutation • Mutation adds variation to population • It is, by itself not a powerful force • Imagine we have the following freq:a=0.9 and A=0.1 • Say, A is mutated to a at a rate of 1 copy/10,000 generations • Back mutations rarely happen • Observe

3. Normally, they would produce alleles at the freq:A=0.9 and a=0.1. Mutation has converted them to:A=0.9-(0.9x0.0001)=0.8999 and a=0.1+(0.0001x0.9)=0.10009

4. Mutation and rate of change? • Allele frequency change occurs slowly!! • Not a big deal by itself! • This example is at a quick rate of mutation

5. Over long periods, mutation can change allele frequencies

6. Mutation and selection • Mutation is a potent evolutionary force when tied to selection • Lenski (1994) took 12 populations of cells and grew them on nutrient poor media (selective environment). • He then took subsamples of each population daily for 1500 days and grew them in fresh media for 10,000 generations • Samples were frozen (still living) at regular intervals. This was so relative fitness of ancestors and descendants could be compared. • He also measured cell size. • Individuals grown in harsh environments produced mutations that allowed it to reproduce quicker • The time from the appearance of a mutation to the fixation of that was so quick we can almost not see it on a graph

8. Mutation-selection balance • The rate at which deleterious alleles are being eliminated is equal to the rate at which new copies are made • q=sqrt(u/s), where q is the equilibrium frequency, u is the mutation rate and s is the selection coefficient. • Ranges from 0-1. This tells us the degree of selection against the mutation. If selection coefficient is small and and mutation rate is high, then the equilibrium frequency of that allele will be high.

9. Mutation-Selection Example • Spinal muscular atrophy is a neurodegenerative disease and is caused by deletions in the gene telSMN on chromosome 5. • Second most common autosomal recessive allele • It has a freq of 0.01 in Caucasian population and has a selection coefficient of 0.9. • You would expect this allele to become extinct, however, it occurs at 1/100 • If we substitute allele freq. for q and selection coefficient for s and solve for u, we get a number that is 9.0 x 10-5 mutations per telSMN allele per generation • When we examine 340 individuals, it was found that 7 of the parents did not have this mutation (brand new mutation) • This rate is 1.1 x 10-4 • Very close to estimate

10. Is Cystic fibrosis maintained by mutation-selection balance? • Most common genetic disease • LOF of CFTR gene. This is a cell surface protein that is expressed in the lungs and prevents bacterial (Pseudomonas) infection • People of European ancestry seem to have this at a frequency of 0.02. • Using the equation in Box 5.10, we find that the mutation rate creating the new allele would have to be very high (4 x 10-4) with a selection coefficient of 1.0 to maintain an allele frequency of 0.02. • However, the real mutation rate is 6.7 x 10-7. Therefore, the frequency at 0.02 cannot be maintained by a steady supply of mutations • Is it possible, the allele is being maintained by overdominance…heterozygote superiority?

11. Pseudomonas

12. Cystic fibrosis and het. superiority? • It is possible that heterozygous individuals cystic fibrosis are resistant to typhoid fever? • The CFTR protein is also found in the gut. • Typhoid bacteria (Salmonella) exploit this protein to cross the gut and increase infection • If you look at normal CFTR in homozyg., het., and homoz. with loss of both CFTR (F508) copies..you see

14. Selection for cyst fibrosis gene after a typhoid outbreak

15. Migration • The movement of alleles between populations • Migration can be caused by anything that moves alleles. Dispersal of animals, pollen on the wind etc.

16. Amounts of gene flow? What about distance?

17. Migration can obviously change allele frequencies!!

18. Migration as a mechanisms of evolution • Water snakes (Nerodia sipedon) in Lake Erie come in two color phases: banded and unbanded • This is a two allele system • Banded dominant to unbanded • The mainland has really only banded • The islands may have both

21. Lake Erie water snakes • It was found that, when basking on islands, the unbanded snakes are more cryptic and thus remain hidden better. • Why wouldn’t selection cause the unbanded pattern to go to fixation? • Migration. Every year, banded snakes migrate from the mainland and introduce fresh banded alleles • Therefore, migration offsets selection • https://www.youtube.com/watch?v=-A468qN5kS0

22. A= UNBANDED B=INTERMEDIATE C=INTERMEDIATE D=STRONGLY BANDED

23. Unopposed migration • Migration may be opposed by selection • If not, migration tends to homogenize populations • If gene flow from the mainland to the island was not opposed by selection, than the island would be homogenized by banded color patterns • Fst statistics predict the amount of allelic variation from 0-1. High numbers indicate high variation

24. Age of flower populations and diversity Young=founded from many alleles Intermediate=migration homogenizes population Old=Competition Disease leaves only few representatives, no new migration

25. Population Genetics 10: Genetic Drift

26. What is drift? • Results from the violation of the assumption of infinite population size • It is equivalent to sampling error or choosing too small of a sample size • In a small population, chance outcomes differ from theoretical expectations • It does not result in adaptation, but does change allele frequencies • https://www.youtube.com/watch?v=mjQ_yN5znyk

27. Small population with 10 individuals

28. Possible outcome when choosing the 10 mice each generation

29. As sample size increases, values meet expectations

30. Founder effect • Small founder populations probably have a different frequency of alleles • This is a result of sampling error • For example, if a continental population of lizards has 35 alleles at a single locus, then the probability=0 that 15 lizards floating away from that population contains all of the alleles

31. Founder effect example • Sonya Clegg studied the effects of migration of Silvereyes from Tazmania to Islands surrounding New Zealand. • Six Microsatellite loci were examined on each population

33. Latest colonization

34. Founder effects in humans • Pingelapese people are descended from 20 individuals following a typhoon and famine • An individual carrying the LOF for the CNGB3 (protein crucial for normal color vision) • Normally, only 1/20,000 people are effected with Achromatopsia • Of the 3,000 Pingelapese, 1/20 have this condition

35. Fixation and loss of diversity are related to sample size

38. Loss of heterozygosity • As alleles drift to fixation or loss, heterozygosity also declines • If we start with Allele A at 73% and allele a at 27%, then each of them proceeds to fixation at a probability equal to their allele frequency • Hg+1=Hg[1-1/2N]. Heterozygosity is always being lost between 1/2 and 1 • If you had only 50 breeding pairs of animals in the world, and you bred them randomly, then you still see a loss of 1% heterozygosity per year

39. Experimental Study on Loss of Heterozygosity • Buri (1956) kept 107 populations of fruit flies for 19 generations. • He only bred 8 males and 8 females from each generation. • A particular allele began 0.5

40. 107 pop. Total By the end of the experiment, 28 pop had become fixed at 0. 30 Pop fixed at 1 Overall they remained symmetric around 0.5

41. Random fixation in natural populations • Templeton (1990) studied collared lizards in Missouri • This lizard normally inhabits desert land • In the past 8,000-4,000 years, Missouri has become wetter and isolated these desert habitats into glades • Fire suppression is further isolating the glades and lizards…they will not migrate through woods to other glades

43. Most are fixed for one type of mtDNA haplotype

44. Problems with loss of heterozygosity • If a pathogen kills one lizard in a glade, then it could kill them all. Why? because they are all have identical genotypes • Lizards would not be able to evolve a response as biological or physical environment changes • In fact 2/3 of 130 glades in Missouri contained no lizards • How to save them? • Introduce new genetic lines of collared lizards • Restore fire regimes…thus increasing migration

45. Genetic Diversity Increases with Population size

46. Mutation vs Substitution Mutation=creation of new allele Substitution= fixation of new mutation (Allele) When genetic drift is only process, mutation rate= sub. Rate (box 7.5)

47. Genetic Drift and Molecular Evolution • Neutral Theory (Kimura) says that advantageous mutations are rare and that most genes are neutral. Therefore evolution generally occurs by drift • Selectionists (Gillespie) advantageous mutations are common (enough to matter) and that the rate of substitution occurs by selection • Drift is a non-adaptive mechanism of evolution

48. Neutral Theory • By the mid-60’s, amino acid sequences for hemoglobin and cytochrome c were determined. • It was found by Kimura that when comparing rate of substitution of AA for horses and humans (using fossils to calibrate) was extremely high. • Zuckerland and Pauling also determined that the rate AA substitution was clock-like. Not what you would expect if selection should act rapidly during times of environmental change

49. Kimura’s Neutral Theory • Beneficial mutations are largely inconsequential. • Rate of molecular evolution is equal only to the rate of mutation • Strangely, in spite of drift, Kimura says that population size does not matter in terms of fixation for new truly neutral alleles • Positive natural selection is excluded, because the vast number of mutations are neutral

50. Patterns in DNA sequence divergence • Use pseudogenes as the paradigm of neutral evolution • The divergence rates in pseudogenes should be equal to the neutral rate…the highest observed in genomes.