1. Please feel free to chat amongst yourselves until we begin at the top of the hour. 1

2. Seminar Agenda Population Genetics Self Assessment Questions Questions & Answers 2

3. 3 Molecular evolution The discovery that DNA is the genetic material made it possible to compare corresponding genes even in distantly related species DNA and protein sequences contain information about evolutionary relationships among species Comparative studies of macromolecules, the study of how and why their sequences change through time constitutes molecular evolution

4. 4 Accumulation of sequence differences through time is the basis of molecular systematics, which analyses them in order to infer evolutionary relationships A gene tree is a diagram of the inferred ancestral history of a group of sequences A gene tree is only an estimate of the true pattern of evolutionary relations Taxon = the source of each sequence Molecular evolution

5. 5 Fig. 14.1

6. 6 Rate of sequence evolution = the fraction of sites that undergo a change in some designated time interval = number of replacements per site per billion years Rates of evolution can differ dramatically from one protein to another Molecular evolution

7. 7 There are different kind of nucleotide sites and nucleotide substitutions depending on their position and function in the genome Synonymous substitution = no change in amino acid sequence = primarily at the third codon position Nonsynonymous substitution = amino acid replacement Rates of evolution of nucleotide sites differ according to their function Molecular evolution

8. 8 Fig. 14.3

9. 9 New genes usually evolve through duplication and divergence Orthologous genes = duplicated as an accompaniment to speciation, retain the same function Paralogous genes = duplicated in the genome of the same species, acquire new or more specialized function Pseudogenes = duplicated genes that have lost their function Molecular evolution

10. Speciation Comparison of Related Sequences from Different Species Can Give Clues to Evolutionary Relationships Among Proteins Protein Families - thought to arise by two different evolutionary processes, gene duplication and speciation. Lodish et al., Molecular Cell Biology, Fifth Edition. 10

11. Protein families=homologous (Speciation) (Duplication) Lodish et al., Molecular Cell Biology, Fifth Edition. 11

12. What information do you think scientists gain by examining the homology of protein sequence among various species? 12

13. Information gained from species comparison Evolution of proteins Usefulness of animal models Will the animal models, such as the mouse and rat, be useful? Is the protein the same in the mouse and rat? Conserved protein regions that may be critical for a particular function 13

14. BLAST: basic local alignment search tool NF1: neurofibromatosis=GAP - GTPase accelerator protein Why search using protein rather than DNA sequence? http://www.ncbi.nlm.nih.gov/ 14 Lodish et al., Molecular Cell Biology, Fifth Edition.

15. 15 Population genetics = application of genetic principles to entire populations of organisms Population = group of organisms of the same species living in the same geographical area Subpopulation = any of the breeding groups within a population among which migration is restricted Local population = subpopulation within which most individuals find their mates Population Genetics

16. 16 Population Genetics Gene pool = the complete set of genetic information in all individuals within a population Genotype frequency = proportion of individuals in a population with a specific genotype Genotype frequencies may differ from one population to another Allele frequency = proportion of any specific allele in a population Allele frequencies are estimated from genotype frequencies

17. 17 Mating Systems Random mating means that mating pairs are formed independently of genotype Random mating of individuals is equivalent of the random union of gametes Assortative mating = nonrandom selection of mating partners; it is positive when like phenotypes mate more frequently than would be expected by chance and is negative when reverse occurs Inbreeding = mating between relatives

18. 18 Inbreeding Inbreeding means mating between relatives Inbreeding results in an excess of homozygotes compared with random mating In most species, inbreeding is harmful due to rare recessive alleles that wouldn’t otherwise become homozygous Fig. 14.9Fig. 14.23

19. AP Biology Measuring Evolution of Populations www.explorebiology.com

20. AP Biology 5 Agents of evolutionary change MutationGene Flow Genetic DriftSelection Non-random mating www.explorebiology.com 20

21. AP Biology Populations & gene pools  Concepts  a population is a localized group of interbreeding individuals  gene pool is collection of alleles in the population  remember difference between alleles & genes!  allele frequency is how common is that allele in the population  how many A vs. a in whole population www.explorebiology.com 21

22. AP Biology Evolution of populations  Evolution = change in allele frequencies in a population  hypothetical: what conditions would cause allele frequencies to not change?  non-evolving population REMOVE all agents of evolutionary change 1. very large population size (no genetic drift) 2. no migration (no gene flow in or out) 3. no mutation (no genetic change) 4. random mating (no sexual selection) 5. no natural selection (everyone is equally fit) www.explorebiology.com 22

23. AP Biology Hardy-Weinberg equilibrium  Hypothetical, non-evolving population  preserves allele frequencies  Serves as a model (null hypothesis)  natural populations rarely in H-W equilibrium  useful model to measure if forces are acting on a population  measuring evolutionary change W. Weinberg physician G.H. Hardy mathematician www.explorebiology.com 23

24. AP Biology Hardy-Weinberg theorem  Counting Alleles  assume 2 alleles = B, b  frequency of dominant allele (B) = p  frequency of recessive allele (b) = q  frequencies must add to 1 (100%), so: p + q = 1 bbBbBB www.explorebiology.com 24

25. AP Biology Hardy-Weinberg theorem  Counting Individuals  frequency of homozygous dominant: p x p = p 2  frequency of homozygous recessive: q x q = q 2  frequency of heterozygotes: (p x q) + (q x p) = 2pq  frequencies of all individuals must add to 1 (100%), so: p 2 + 2pq + q 2 = 1 bbBbBB www.explorebiology.com 25

26. AP Biology H-W formulas  Alleles:p + q = 1  Individuals:p 2 + 2pq + q 2 = 1 bbBbBB BbBbbb www.explorebiology.com 26

27. AP Biology Using Hardy-Weinberg equation q 2 (bb): 16/100 =.16 0.4 q (b): √.16 = 0.4 0.6 p (B): 1 - 0.4 = 0.6 q 2 (bb): 16/100 =.16 0.4 q (b): √.16 = 0.4 0.6 p (B): 1 - 0.4 = 0.6 population: 100 cats 84 black, 16 white How many of each genotype? population: 100 cats 84 black, 16 white How many of each genotype? bbBbBB p 2 =.36 2pq=.48 q 2 =.16 Must assume population is in H-W equilibrium! www.explorebiology.com 27

28. AP Biology Using Hardy-Weinberg equation bbBbBB p 2 =.36 2pq=.48 q 2 =.16 Assuming H-W equilibrium Sampled data bbBbBB p 2 =.74 2pq=.10 q 2 =.16 How do you explain the data? p 2 =.20 2pq=.64 q 2 =.16 How do you explain the data? Null hypothesis www.explorebiology.com 28

29. AP Biology Application of H-W principle  Sickle cell anemia  inherit a mutation in gene coding for hemoglobin  oxygen-carrying blood protein  recessive allele = H s H s  normal allele = H b  low oxygen levels causes RBC to sickle  breakdown of RBC  clogging small blood vessels  damage to organs  often lethal www.explorebiology.com 29

30. AP Biology Sickle cell frequency  High frequency of heterozygotes  1 in 5 in Central Africans = H b H s  unusual for allele with severe detrimental effects in homozygotes  1 in 100 = H s H s  usually die before reproductive age Why is the H s allele maintained at such high levels in African populations? Suggests some selective advantage of being heterozygous… www.explorebiology.com 30

31. AP Biology Malaria Single-celled eukaryote parasite (Plasmodium) spends part of its life cycle in red blood cells 1 2 3 www.explorebiology.com 31

32. AP Biology Heterozygote Advantage  In tropical Africa, where malaria is common:  homozygous dominant (normal)  die or reduced reproduction from malaria: H b H b  homozygous recessive  die or reduced reproduction from sickle cell anemia: H s H s  heterozygote carriers are relatively free of both: H b H s  survive & reproduce more, more common in population Hypothesis: In malaria-infected cells, the O 2 level is lowered enough to cause sickling which kills the cell & destroys the parasite. Hypothesis: In malaria-infected cells, the O 2 level is lowered enough to cause sickling which kills the cell & destroys the parasite. Frequency of sickle cell allele & distribution of malaria www.explorebiology.com 32

33. AP Biology Any Questions?? www.explorebiology.com

34. Any questions? 34