From DNA Mutations to Selectable Phenotypes to Genetically Diverged Populations

1. From DNA Mutations to Selectable Phenotypes to Genetically Diverged Populations Teaching Evolutionary Principles by Integrating Biology’s Sub-disciplines Jim Smith Michigan State University Lyman Briggs College Department of Entomology jimsmith@msu.edu • 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. Alleles at a locus Basic Principles of Mendelian Genetics R R Genotype Phenotype

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

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

7. Integrating Across Sub-disciplines

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

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

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

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

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

13. Gregor Mendel • Observed 5474 round seeds (dominant) and 1850 wrinkled seeds (recessive) • 5474/1850 = 2.96:1 • Do a c2-test • Is this a 3:1?

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

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

16. R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R r r r r r r r r r A Population of Peas

17. r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r r A Population of Peas

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

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

20. Beach Mice - The Mc1r locus and MC1R ProteinHoekstra 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 R65C amino acid substitution bind -MSH less well and produce less cAMP From: Barsh 1996 Trends in Genetics

24. R65C 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 a-MSH and the lower amount of cAMP produced by individuals with the R65C 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 • Muscle attached to sagittal crest on top of head • Continued to modern apes • Allows for hard chewing • Important for raw vegetable diet Currie P. 2004. Nature 428: 373-374. • Stedman H, et al. 2004. Myosin gene mutation correlated with anatomical changes in the human lineage. Nature 428: 415-418.

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

30. How did this happen? • 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 • Temporalis and Masseter Muscles • 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 Guilfoile P. 1997. Wrinkled Peas & White-Eyed Fruit Flies: The Molecular Basis of Two Classical Genetic Traits. The American Biology Teacher 59: 92-95. 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 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