1. From DNA Mutations to Selectable Phenotypes to Genetically Diverged Populations Jim Smith Michigan State University Lyman Briggs College Department of Entomology jimsmith@msu.edu Teaching Evolutionary Principles by Integrating Biology’s Sub-disciplines n Goals for today’s session Why were Mendel’s peas wrinkled? Cell biology of natural selection on a beach. People are evolving, too! wcco.com

2. On the Origin of Species Darwin’s Logic  Variation under Domestication  We can easily see how people have artificially selected “favored races” of pigeons, sheep, roses and dahlias.  Natural Selection  One can easily also envision how this same “selection” process can occur naturally, in the wild. The patterns of variation we observe in nature support this idea. Downe House from the Sand Walk

3. We’ll Follow Similar Logic Today Mendel’s Peas  Artificial Selection  Wrinkled Peas are sweeter, and therefore people will tend to select them and propagate them. Hopi’s Mice  Natural Selection  Mice with white coats on white sand beaches are less visible to prey.  Thus, they are less subject to predation and selectively survive. goodlifefarm.com Hoekstra et al. 2006. Science 313: 101–107.

4. Basic Principles of Mendelian Genetics Alleles at a locus Genotype Phenotype RR

5. R Mother Rr Female gametes R r Father Rr Male gametes R r RrRR Rrrr Resulting genotypes: 1/4 RR : 1/2 Rr : 1/4 rr Resulting phenotypes: 3/4 : 1/4 Freeman 1e Fig. 10.7 R = Dominant allele for seed shape (round) r = Recessive allele for seed shape (wrinkled) = Round-seeded phenotype = Wrinkled-seeded phenotype Mendelian Genetics

6. Why are wrinkled peas wrinkled? (use the word, “protein” in your answer!) R Hint: What does “R” do? Freeman 1e Fig. 10.2

7. Integrating Across Sub-disciplines

8. The Central Dogma of Molecular Biology n Connect to Mendelian Genetics n Connect to Evolution

9. What does the “R” gene do? R How does the SBEI protein lead to round seeds? It gives rise to highly branched starch (amylopectin) Highly branched starch in the seeds leads to seeds with low water content. When the seeds dry, they stay round. Freeman 1e Fig. 10.2 Modified from Campbell 4e Fig. 5.6

10. Molecular Basis of Wrinkled vs. Round Peas R allele  Functional SBE Protein 800 bp fragment of DNA inserted R protein r protein r allele  Non-Functional SBE Courtesy of Dr. April Cognato, Mich. St. Univ., Dept. Zoology

11. R 3550 nucleotides! What does the “R” symbol represent?

12. What does the “R” gene do? R The “R” gene DNA encodes a starch branching enzyme protein (SBEI)! A polypeptide of approx. 960 amino acids

13. Gregor Mendel n Observed 5474 round seeds (dominant) and 1850 wrinkled seeds (recessive) 5474/1850 = 2.96:1 Do a  2-test Is this a 3:1?

14. Basic Principles of Evolution Phenotypic Variation Environment w/ Selection Evolved Population n Connect to Mendelian Genetics n Connect to Cell and Molecular Biology

15. Bridging Mendel and Darwin n Observed 5474 round seeds (dominant) and 1850 wrinkled seeds (recessive) 5474/1850 = 2.96:1 n How would the wrinkled allele (r) go to fixation in a population?

16. rrrrRRRRRRRRrRrrRRRRRRRRRrRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRrRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRRR A Population of Peas

17. rrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrr

18. How do new species evolve? From:http://evolution.berkeley.edu/e volibrary/article/_0/history_20

19. Merging Genetics, Molecular Biology, and Evolution Phenotypic Variation Environment w/ Selection Evolved Population Alleles at a locus Genotype Phenotype DNA RNA Protein R Peas Connect Parallel Paths!!

20. Beach Mice - The Mc1r locus and MC1R Protein Hoekstra et al. 2006

21. Mice living on exposed white sand beaches along the Gulf Coast have different Mc1r allele frequencies

22. The mutant Mc1r gene has a single C  T substitution, leading to the substitution of Cysteine for Arginine at position 65 in the MC1R protein

23. MC1R proteins (polypeptides) with the R 65 C amino acid substitution bind  -MSH less well and produce less cAMP From: Barsh 1996 Trends in Genetics

24. R 65 C MC1R Proteins Function Differently in Melanocytes than their Counterparts Steiner et al. 2009. Mol Biol Evol 26: 35-45.

25. Clicker Q1. The ultimate reason for the lighter coat colors of the mice on the white sand Gulf Coast beaches was: A. predation by hawks and other carnivores on beach mice that do not carry the mutant allele. B. a substitution of Cys for Arg at position 65 of the MC1R protein. C. a substitution of T for C at position 193 of the Mc1r gene nucleotide sequence. D. the failure of melanocytes to lay down melanin pigment in the coat hairs of the lighter colored beach mice. E. the poorer binding affinity for  -MSH and the lower amount of cAMP produced by individuals with the R 65 C MC1R protein.

26. Clicker Q2. The C  T substitution at position 193 of the Mc1r gene: A. arose by a mutation in the beach mouse populations in response to a need for protection from predation. B. leads to the failure of melanocytes to make an MC1R protein. C. arose by a mutation, which increased in frequency because it was selectively advantageous in the beach mouse populations. D. had no effect on the beach mouse populations. E. produced an alternate allele that was detrimental to mice on the white sand beaches.

27. Humans Are Evolving, Too!! Organismal Biology Honors Presentation [2 Lyman Briggs students]

28. Jaw Muscle-Ape Archaic Ape, Humanoids- heavy jaw (myofascial) muscles Archaic Ape, Humanoids- heavy jaw (myofascial) muscles Muscle attached to sagittal crest on top of head Muscle attached to sagittal crest on top of head Continued to modern apes Continued to modern apes –Allows for hard chewing –Important for raw vegetable diet Stedman H, et al. 2004. Myosin gene mutation correlated with anatomical changes in the human lineage. Nature 428: 415-418. Currie P. 2004. Nature 428: 373-374.

29. Jaw Muscle-Humans Smaller jaw muscles then apes Smaller jaw muscles then apes –Decrease in plant consumption –More reliance on hands Decrease in muscles eliminated sagittal crest Decrease in muscles eliminated sagittal crest Currie P. 2004. Nature 428: 373-374.

30. How did this happen? Myosin Heavy Chain (MYH) Myosin Heavy Chain (MYH) –Critical proteins in sarcomere –Myosin binds to actin and uses ATP to pull itself  Give contractile force to skeletal muscle –Different types for contraction in different muscles –Loss of MYH gene cause large loss of muscle

31. MYH: Humans vs. Chimps MYH 16 in both Human & Chimps MYH 16 in both Human & Chimps –Temporalis and Masseter Muscles Human gene mutated Human gene mutated –Accumulate less MYH 16 protein Seven non-human species compared to six geographically dispersed human populations

32. Bibliography and Resources Wrinkled Peas n Guilfoile P. 1997. Wrinkled Peas & White-Eyed Fruit Flies: The Molecular Basis of Two Classical Genetic Traits. The American Biology Teacher 59: 92-95. n Bhattacharyya MK, et al. 1990. The wrinkled-seed character of pea described by Mendel is caused by a transposon-like insertion in a gene encoding starch-branching enzyme. Cell 60: 115-122. Beach Mice n Hoekstra HE, Hirschmann RJ, Bundey RA, Insel PA, Crossland JP. 2006. A single amino acid mutation contributes to adaptive beach mouse color pattern. Science 313: 101–107. Human Jaws  Stedman H, et al. 2004. Myosin gene mutation correlated with anatomical changes in the human lineage. Nature 428: 415-418. Slides from today’s session: http://www.msu.edu/user/jimsmith/nabt_2010.pdf