Dr. Carol Eunmi Lee University of Wisconsin, Madison

1. Dr. Carol Eunmi Lee University of Wisconsin, Madison History of Evolutionary Thought: The Grand Evolutionary Synthesis

2. Today’s OUTLINE: (1) The Sources of Confusion (2) Reconciling Mendel and Darwin (3) The Main Tenets of the Evolutionary Synthesis (4) Key Developments since the Synthesis (5) Gaps in our Understanding Today

3. Charles Darwin(1809-1882) Last time we discussed Darwin’s contributions to evolutionary thinking

4. Darwin’s contribution: “Population Speciation as a result of Natural Selection” • More offspring are produced than can survive • Limited resources and competition for resources • There is heritable variationin a population • Individuals better adapted to environment survive • Survivors leave more offspring (“Survival of the Fittest”) • Thus, averagecharacter of populationis altered

5. But, Darwin’s theory was not complete • Because Darwin knew nothing about mutation, he had no idea how variation was generated in populations • Because Darwin knew nothing about genetics or genes, he had no idea how variation was passed on to offspring(Mendel) • Darwin did not know about nonadaptive evolutionary forces, such as Genetic Drift

6. Mendel’s work held part of the key to what was missing in Darwin’s Theory • Mendel published in 1865… was ignored until 1900 • Presented a mechanism for how traits got passed on “Individuals pass alleles on to their offspring intact” (the idea of particulate (genes) inheritance)

7. Rediscovery of Mendel’s laws of inheritance • In 1900, Mendel’s laws of inheritance were “rediscovered” • Dutch biologist Hugo de Vries, German plant geneticist Carl Correns, and Austrian plant breeder Erich von Tschermak-Seysenegg • Worked out laws of inheritance independently • Discovered Mendel’s work as they were publishing their own • Formed the beginning of the foundation of Genetics: Mendel is considered the “Father of Genetics”

8. Hardy-Weinburg Equilibrium (Lecture 3) • Wilhem Weinberg • January 13, 1908 • G. H. Hardy • July 10, 1908 in Science • Could mathematically show expectations of Mendelian inheritance and whether expectations are realized in nature

9. BUT… Mendel and Darwin’s ideas seemed Incompatible • Mendel: dealt with particulate traits • Darwin: observed continuous traits Q: How would continuous traits get passed on?

10. Selection vs Mutations • Mutations discovered after 1900 Q: If mutations are arising, why need selection... … if things are just mutating?

11. Controversy between Mutationists vs Darwinists Mutationists (+ Mendelianism) • They thought that evolution required only mutations and passing on of discrete traits Darwinists • They thought that evolution required only Natural Selection on continuous variation

12. Discrete vs Quantitative Traits • Discrete trait: a trait that has distinct values, rather than a range of phenotypes, usually encoded by one or a few genes. • Examples: number of fingers, color of Mendel’s peas, sickle cell anemia, ABO blood type, number of eggs in a bird clutch, presence/absence of human widow’s peak, presence/absence of dimples, etc. • Quantitative (continuous) trait: a trait that has a continuum of phenotypes and is encoded by multiple genes. • Examples: body size, height, weight, intelligence (IQ), Running speed, beak shape, hair color, skin color, milk yield of cows, lifespan, etc. • Darwin was unable to clearly see the pattern of inheritance because he studied quantitative variation Frequency Type Frequency Type

13. Proponents of the Darwinist Theory • Proponents of Darwinism were correct about mechanisms of Natural Selection, but they did not understand what Selection was acting on, as they were unaware of the unit of inheritance (genes) or how the variation was passed on to the next generation • They came up with the idea of “Blending inheritance” where offspring gain characteristics of both parents, like mixing colors of paint… but, this was a vague idea that was incorrect • Many of them were Biometricians (statistical types) that thought that evolution was gradually acting on continuous traits

14. Proponents of the Mutationist/Mendelist Theory • Many Prominent Geneticists at the time supported the Mutationist/Mendelist theory • Proponents of the mutationist theory included Hugo de Vries, among those who “discovered” Mendel’s 1900 paper and Thomas Hunt Morgan, founder of Drosophila genetics • Thought that evolution arose through genetic changes (mutations) that were discrete and sudden • New species originated when they mutated from pre-existing species, but this process was independent of natural selection

15. Controversy between Mutationists vs Darwinists The controversy persisted for ~30 years up until the 1930s, during which relatively little progress was made

16. Problems to Resolve: • At the heart was the question of whether Mendelian genetics and Mutation could be reconciled with mechanisms of Natural Selection. • A second issue was whether the broad-scale changes (macroevolution) seen by palaeontologists could be explained by changes seen in local populations (microevolution).

17. Problem caused by: • Binary thinking (Black or White thinking): it’s this or that… “if I’m right, you must be wrong”  When in fact the two or more factors might interact • Inability to see overarching mechanism that could explain a wide range of phenomena: “How could your Hardy-Weinberg (Mendel) explain the inheritance of 5.1 cm, 5.5 cm beak length (continuous characters)?”  When in fact, one principle might govern and explain the different patterns

18. There were other competing ideas of evolution, including Neo-Lamarckianism

19. Genetic Drift • A concept as important as Natural Selection • But, not as prominent on people’s minds • 1872 Gulick: Neutral theory (Genetic Drift) • 1921 A.C. Hagedoorn produced data to support Neutral Theory Genetic Drift

20. The Modern Synthesis 1930s ~ 1940s Also called the “Synthesis of Evolution and Genetics” The synthesis of population genetics (role of mutation, selection, genetic drift), paleontology, systematics Darwin and Mendel Reconciled

21. The Modern Synthesis 1930s ~ 1940s Also called the “Synthesis of Evolution and Genetics” Among the Greatest Scientific Revolutions of the Century

22. Three of the "architects" of the evolutionary synthesis:G. Ledyard Stebbins, Jr., George Gaylord Simpson, Theodosius Dobzhansky Photograph from Smocovitis, V. B. 1997. G. Ledyard Stebbins, Jr. and the evolutionary synthesis (1924-1950). American Journal of Botany 84: 1625-1637.

23. The Evolutionary Synthesis was important because many scientists from different fields convened to discuss the evolutionary mechanisms and clear up confusion and inconsistencies

24. Some Key Tenets of the Modern Synthesis • Populations are the units of Evolution • Mendel vs Darwin: continuous traits are also coded by particulate genes, but many genes • Mutation vs Selection: Mutations are sources of genetic variation upon which Selection acts • Natural Selection and Mutation are not the only evolutionary forces. Examples: Genetic Drift, Recombination • Microevolutionary processes, such as Drift, Selection, Mutation, lead to Macroevolutionary changes (such as speciation)

25. Some Tenets of the Evolutionary Synthesis • The phenotype is different from the genotype • Acquired characters (phenotypic plasticity) are not inherited • Traits are inherited via genes, and they do not “blend” with other genes (Darwin was wrong about this one) • Genes mutate, resulting in different alleles • Evolution occurs at the population level, due to a change in proportions of individuals with different genotypes • Changes in proportion in a population could occur via random genetic drift (Sewall Wright) or Natural Selection… the rate of mutation is usually too low to cause large changes in proportions • Even very weak natural selection could cause substantial changes over a longer time scale • Mutations generate the genetic variation upon which natural selection acts • Microevolutionary processes lead to Macroevolutionary changes (speciation) • All organisms on the planet are related to one another in a great “tree of life”, and have diverged by branching from common ancestors • Gaps in the fossil record are likely due to incompleteness of the fossil record. Gradual changes seen in many parts of the fossil record suggest gradual changes over time

26. Mutation vs Selection and Reconciling Mendel and Darwin

27. Mutation vs Selection • And Reconciling Mendel and Darwin • continuous and discrete traits could follow the same principles of inheritance (Mendel), just that continuous traits are coded by many genes (loci) • If there are many genes (loci) coding for a trait, rather than one, the offspring look intermediate between the parents (looks like “blending inheritance”) • BUT, the SAME Mendelian patterns of inheritance apply, it’s just that you don’t see the particulate inheritance of each gene in the offspring, but the average effect across all the genes affecting the trait

28. How do you deal with quantitative traits? (2nd point below) • Hardy Weinberg: multiple alleles: • 3 alleles: (p + q + r)2 which expands to... p2 + 2pq + q2 + 2pr + 2qr + r2 =1.0 • 4 alleles: (p + q + r + s)2 • Hardy Weinberg: multiple loci • HW principle still applies to each locus independently • Need to use principles of Quantitative Genetics to examine effects of multiple loci

29. The Population Geneticists JBS Haldane Sewall Wright Mathematical theory of population genetics showed that mutation and selection TOGETHER cause adaptive evolution: Mutation is NOT an alternative to Natural Selection, but the raw material upon which natural selection acts. RA Fisher

30. Fisher vs Wright Both appreciated the importance of Natural Selection AND Genetic Drift But they argued about the relative importance

31. Ronald Aylmer Fisher (1890-1962) Background in math, physics, astronomy, and genetics Made key contributions to the field of Statistics

32. Ronald Aylmer Fisher (1890-1962) • Natural selection occurs in large populations • Many genes are involved • Mutations are the main substrate for selection Other Contributions: • Adding mathematical rigor into the theory of selection • Elegant synthesis of Mendelian inheritance into the Theory of Selection • Important developments in Statistics (ANOVA)

33. Sewall Wright(1889-1988) Heavily influenced by examples from agriculture Worked for the US Dept of Agriculture: breeding in guinea pigs and cattle Became a professor at UW-Madison in Genetics

34. Sewall Wright(1889-1988) • Inbreeding and Genetic Drift are important for creating new gene interactions • These new gene interactions (epistasis caused by new recombinations) are the main substrate for selection

35. The Population Geneticists If you want to read more about this topic, this book is a good read

36. Reconciling Microevolutionary Mechanisms and Macroevolutionary processes

37. Microevolution  Macroevolution Ernst Mayr George Gaylord Simpson G. Ledyard Stebbins Bernhard Rensch and others George Gaylord Simpson Ernst Mayr Microevolutionary processes within species account for macroevolution among species (Lecture #18) That is, mutation, recombination, natural selection, and other processes that act within species (microevolution) are the SAME mechanisms that account for the origin of new species and major long term evolution (macroevolution) (Lecture #18)

38. James F. Crow(1916-2012) University of Wisconsin, Madison His work has touched on nearly every area of evolutionary genetics -will discuss some of his contributions in Lecture #7 http://www.genetics.wisc.edu/CATG/crow/index.html

39. The Importance of Natural Selection vs Genetic Drift Ongoing debate after the Evolutionary Synthesis

40. Even after the synthesis the relative importance of Natural Selection and Genetic Drift was debated • During the Evolutionary Synthesis, Sewall Wright focused more on importance of Genetic Drift, whereas Fisher focused on Natural Selection • Shortly after the Evolutionary Synthesis many focused on selection to the point of assuming that most phenotypes were the result of Natural Selection • Emphasis on Genetic Drift resurged in the 1970s, 80s with Kimura’s “Neutral Theory” • Then in the 2000s and 2010s interest in Selection increased with the ability to detect signatures of Natural Selection in genome sequence data

41. Motoo Kimura (1924-1994) The Neutral Theory of Molecular Evolution Classic Paper: Kimura, Motoo. 1968. Evolutionary rate at the molecular level. Nature. 217: 624–626. Classic Book: Kimura, Motoo (1983). The neutral theory of molecular evolution. Cambridge University Press.

42. The Neutral Theory of Molecular Evolution (Lecture #6) • The Neutral theory posits that the vast majority of evolutionary change at the molecular level is caused by random genetic drift rather than natural selection. Motoo Kimura • Neutral theory is not incompatible with Darwin's theory of evolution by natural selection: adaptive changes are acknowledged as present and important, but hypothesized to be a small minority evolutionary change. • Recent tests of selection have found that in many cases evolution is not neutral, even in non-coding regions of the genome. • Nevertheless, the neutral theory is useful as a null hypothesis, against which selection could be tested.

43. While the Evolutionary Synthesis was a HUGE leap in the right direction, there were a few tenets that required modification(as a result of new discoveries in Genetics)

44. Some Tenets of the Evolutionary Synthesis • The phenotype is different from the genotype • Acquired characters (phenotypic plasticity) are not inherited –not always true • Traits are inherited via genes, and they do not “blend” with other genes (Darwin was wrong about this one) • Genes mutate, resulting in different alleles • Evolution occurs at the population level, due to a change in proportions of individuals with different genotypes • Changes in proportion in a population could occur via random genetic drift (Sewall Wright) or Natural Selection… the rate of mutation is usually too low to cause large changes in proportions • Even very weak natural selection could cause substantial changes over a longer time scale • Mutations generate the genetic variation upon which natural selection acts • Microevolutionary processes lead to Macroevolutionary changes (speciation) • All organisms on the planet are related to one another in a great “tree of life”, and have diverged by branching from common ancestors • Gaps in the fossil record are likely due to incompleteness of the fossil record. Gradual changes seen in many parts of the fossil record suggest gradual changes over time –not always true

45. Completing the Synthesis Advances in Genetics • Epigenetic Inheritance (Lecture #9) • Some genetic changes could lead to radical changes in phenotype (Lecture #7) • Polyploidization seen often in plants • Changes in developmental genes • Regulatory Evolution • Transposons

46. Evolution at the Molecular Genetic Level Which types of mutations predominate and contribute to adaptations more often? • Structural vs Regulatory? • Is phenotypic evolution occurring predominantly at the level of gene products (e.g. proteins) or at the level of gene regulation (e.g. transcription, RNA processing, translation, etc.)? • cis-Regulation vstrans-Regulation? • Is regulatory evolution occurring predominantly at the level of cis-regulatory elements (e.g. promoter, enhancers) or at the level of trans-acting factors (e.g. transcription factors, etc.)? More on Lectures on Molecular Evolution (Lecture #13)

47. The role of Epigenetics(Lecture #9) • Lamarck Revisited • Lamarck was incorrect in thinking that the inheritance of acquired characters is the main mechanism of evolution • However, we do now know that the inheritance of acquired characters does happen sometimes, through the inheritance of epigenetic modifications

48. Evolution of Development(Lecture #26) • How small changes in developmental genes (like Hox genes) could radically cause the evolution of body plans • Will talk more about this when I get to lecture on Animal Diversity

49. Role of Genomics(Lectures #15, 16) • How does the whole genome evolve? • How does selection act on networks of interacting genes? • How many and which genes are involved in the formation of new species?

50. Today: Genome Evolution and Systems Biology • How do multiple genes interact? • How do multiple genes affect a phenotype? • Systems Biology: How does selection act on interacting gene networks? • Evolution of Genome Architecture