1. History of Evolutionary Thought:
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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
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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. 11/29/2018
Charles Darwin ( )
Last time we discussed Darwin’s contributions to evolutionary thinking

4. Darwin’s contribution:
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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 variation in a population
Individuals better adapted to environment survive
Survivors leave more offspring (“Survival of the Fittest”)
Thus, average character of population is altered

5. But, Darwin’s theory was not complete
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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. 11/29/2018
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)
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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
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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
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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
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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
Darwin was unable to clearly see the pattern of inheritance because he studied quantitative variation
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.
Frequency
Type
Frequency
Type

16. Discrete vs Quantitative Traits
Darwin was unable to clearly see the pattern of inheritance because he studied quantitative variation
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.
Frequency
Type
Example: human height encoded by ~423 genes:

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

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
11/29/2018
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
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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
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Both appreciated the importance of Natural Selection AND Genetic Drift
But they argued about the relative importance

35. Ronald Aylmer Fisher (1890-1962)
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Ronald Aylmer Fisher ( )
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)
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Ronald Aylmer Fisher ( )
• 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)
Most of you gave a Fisherian answer to the question on how evolution occurs

37. 11/29/2018
Sewall Wright ( )
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. 11/29/2018
Sewall Wright ( )
• 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. If you want to read more about this topic, this book is a good read
The Population Geneticists
11/29/2018
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
Ernst Mayr
George Gaylord Simpson
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
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James F. Crow ( )
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

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

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 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.
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.

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)

51. 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

52. Completing the Synthesis
Advances in Genetics
Epigenetic Inheritance
Some genetic changes could lead to radical changes in phenotype
Polyploidization, through polyploid hybridization or Whole Genome Duplication
Regulatory Evolution (e.g. transcription factor evolution, as TFs regulate many genes)
 often leads to radical evolution of development
Transposons

53. The role of Epigenetics
Lamarck Revisited
Lamarck was incorrect in thinking that the inheritance of acquired characters is the main mechanism of evolution
However, we now know that the inheritance of acquired characters does happen sometimes, through the inheritance of epigenetic modifications (Epigenetic Inheritance)
Yet, the extent to which epigenetic inheritance occurs is still not known and controversial (experimentally difficult to confirm), especially in animals

54. C.H. Waddington --his resurgence
Largely dismissed during the Evolutionary Synthesis attacked for being “Lamarckian” for his ideas on “Genetic Assimilation”
Father of Developmental Biology
Introduced the concept of “Canalization”
Coined the term “Epigenetics”
Conrad Hal Waddington
Interested in the interplay between phenotypic plasticity (response to stress) and selection “Genetic Assimilation”

55. Why did Waddington become popular starting in the 1990’s?
Evo-Devo: Evolution of Development as playing an important role in the evolution of phenotypes
Evolution of developmental program could cause radical phenotypic change
The idea of evolution of canalization and decanalization of a developmental program
Genetic Assimilation: stress could cause decanalization, and the phenotypes that are exposed could then be under selection  creation of “Hopeful Monsters”

56. Evolution of Development (Lecture #26)
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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

57. 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 vs trans-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

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

59. Today: Genome Evolution and Systems Biology
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Today: Genome Evolution and Systems Biology
How do multiple genes interact?
How do multiple genes affect a phenotype?
(questions about the “genotype-phenotype map”)
Systems Biology: How does selection act on interacting gene regulatory networks?
Evolution of Genome Architecture

60. 11/29/2018
Questions:
(1) What were the sources of confusion regarding evolutionary mechanisms leading up to the Evolutionary Synthesis?
(2) What was the Modern (Evolutionary) Synthesis?
(3) What were the main tenets of the Evolutionary Synthesis?
(4) What is the relationship between natural selection, genetic drift, mutations, and recombination?
(5) What were some of the limitations of the Evolutionary Synthesis?
(6) What were some key developments since the Evolutionary Synthesis?
(7) What gaps remain in our understanding today?

61. Sample Exam Questions
1. For several decades "Darwinists" and "Mendelists" battled over the mechanisms of evolution. Which of the following did NOT contribute to this particular conflict? (a) Geneticists/Evolutionary biologists did not understand that continuous and discrete traits follow the same principle of inheritance (b) Geneticists/Evolutionary biologists did not understand that natural selection acts on mutations in a population (c) Mendel worked with discrete traits, whereas Darwin worked with continuous traits, leading to differences in perspectives on inheritance (d) Darwin was unaware of the mechanism or unit of inheritance (e) Darwin was unaware of the mechanisms of Genetic Drift

62. 11/29/2018
Sample Exam Question
2.Which of the following was NOT a tenet of the Evolutionary Synthesis?
(a) Evolution occurs at the level of populations, in terms of changes in allele frequencies, rather than changes at the individual level
(b) Selection could act on traits that are coded by multiple genes
(c) Selection acts on genetic variation in traits that are caused by mutations
(d) Natural Selection and Mutation are the only causes of evolutionary change
(e) Microevolutionary processes within populations lead to Macroevolutionary changes among populations

63. Answers:
1. E (Darwin did not know about Genetic Drift, but that was not a reason for the conflict between the “Darwinists” and “Mendelists”)
2. D