Dr. Carol Eunmi Lee University of Wisconsin, Madison

1. History of Evolutionary Thought: The Grand Evolutionary Synthesis Considered one of the most important Biological Revolutions of the Century Dr. Carol Eunmi Lee University of Wisconsin, Madison

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. Question: • What body of knowledge provided Darwinian theory with the concept of “genes” and inheritance?

7. 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)

8. 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 • These rediscoveries formed the beginning of the foundation of Genetics: Mendel is considered the “Father of Genetics”

9. 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 Mendelian expectations are realized in nature

10. Did the Darwinists accept Mendelian Genetics? • Why or Why Not?

11. PROBLEMS!

12. BUT… Mendel and Darwin’s ideas seemed Incompatible • Mendel’s principles: dealt with particulate (discrete) traits (e.g. yellow vs. green, wrinkled vs. smooth) • BUT, Darwin observed continuous traits (e.g. beak size, body length) Q: So, how would continuous traits get passed on?

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

14. 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

15. 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

16. Discrete vs Quantitative Traits • 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 Example: human height encoded by ~423 genes: http://www.nature.com/ng/journal/v46/n11/full/ng.3097.html

17. 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

18. 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

19. Controversy between Mutationists vs Darwinists Controversy persisted for ~30 years up till the 1930s, during which little progress was made

20. 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).

21. 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

22. 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

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

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

25. 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.

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

27. 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

28. 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

29. With which of these tenets do you agree? • With which do you not agree?

30. Mutation vs Selection and Reconciling Mendel and Darwin

31. 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 for multi-locus traits, 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

32. How do you deal with multi-locus quantitative traits? (2nd point below) • Hardy Weinberg: multiple alleles at a single locus: • 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

33. 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

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

35. Ronald Aylmer Fisher (1890-1962) Background in math, physics, astronomy, and genetics Made key contributions to the field of Statistics Developed the Foundations for the mathematics of Natural Selection

36. 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)

37. 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

38. 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 I’ll talk a lot about Sewall Wright in the lecture on Genetic Drift

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

40. Reconciling Microevolutionary Mechanisms and Macroevolutionary processes

41. 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 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)

42. 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 on Mutations http://www.genetics.wisc.edu/CATG/crow/index.html

43. Professor James Crow Lecture: Selection on Quantitative Traits (multi-locus traits): video.wpt.org/video/1811393836/

44. Moral of the Story • Scientists from different fields should talk to each other • Should avoid binary thinking (this vs. that, right vs. wrong), as different mechanisms might work together in an integrated fashion • We are often biased by what we study (example of continuous vs. discrete traits)

45. After the Evolutionary Synthesis

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

47. 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 RA 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 much of the genome is under selection

48. 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.

49. 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. • Purifying selection (negative selection) could still be acting to remove deleterious mutations from the genome. But, the idea here is that most of the genetic variation within and between populations is due to neutral variation. • **Ongoing debate on the extent to which variation across the genome is caused by genetic drift vs. natural selection

50. 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)