History of
Evolutionary Thought:
The Grand Evolutionary
Synthesis
Dr. Carol Eunmi Lee
University of Wisconsin, Madison
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
Charles Darwin (1809-1882)
Last time we discussed
Darwin’s contributions
to evolutionary thinking
Darwin’s contribution:
“Population Speciation as a result of Natural Selection”
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More offspring are produced than can survive
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Limited resources and competition for resources
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There is heritable variation in a population
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Individuals better adapted to environment survive
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Survivors leave more offspring (“Survival of the
Fittest”)
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Thus, average character of population is altered
But, Darwin’s theory was not complete
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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
Mendel’s work held part of the key to what was
missing in Darwin’s Theory
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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)
Rediscovery of Mendel’s
laws of inheritance
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In 1900, Mendel’s laws of inheritance
were “rediscovered”
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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
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Formed the beginning of the foundation of
Genetics: Mendel is considered the “Father of
Genetics”
Hardy-Weinburg
Equilibrium
(Lecture 3)
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Wilhem Weinberg
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G. H. Hardy
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January 13, 1908
July 10, 1908 in Science
Could mathematically show
expectations of Mendelian
inheritance and whether
expectations are realized in
nature
BUT… Mendel and Darwin’s ideas
seemed Incompatible
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Mendel: dealt with particulate traits
Darwin: observed continuous traits
Q: How would continuous traits
get passed on?
Selection vs Mutations
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Mutations discovered after 1900
Q: If mutations are arising, why
need selection... … if things are
just mutating?
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
Discrete vs Quantitative Traits
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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.
Frequency
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.
Type
Frequency
Type
Proponents of the Darwinist Theory
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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
Proponents of the
Mutationist/Mendelist Theory
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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
Controversy between
Mutationists vs Darwinists
The controversy persisted for ~30 years
up until the 1930s, during which relatively
little progress was made
Problems to Resolve:
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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).
Problem caused by:
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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
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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
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There were other competing ideas of
evolution, including Neo-Lamarckianism
Genetic Drift
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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
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
The Modern Synthesis
1930s ~ 1940s
Also called the “Synthesis of Evolution and
Genetics”
Among the Greatest Scientific
Revolutions of the Century
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.
The Evolutionary Synthesis was important
because many scientists from different
fields convened to discuss the evolutionary
mechanisms and clear up confusion and
inconsistencies
Some Key Tenets of the Modern Synthesis
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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)
Some Tenets of the Evolutionary Synthesis
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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
Mutation vs Selection
and Reconciling Mendel and Darwin
Mutation vs Selection
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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)
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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
How do you deal with quantitative traits?
(2nd point below)
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Hardy Weinberg: multiple alleles:
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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
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HW principle still applies to each locus
independently
Need to use principles of Quantitative
Genetics to examine effects of multiple
loci
The Population Geneticists
JBS Haldane
Sewall Wright
Mathematical theory of population
genetics showed that mutation and
selection TOGETHER cause adaptive
evolution:
RA Fisher
Mutation is NOT an alternative to
Natural Selection, but the raw material
upon which natural selection acts.
Fisher vs Wright
Both appreciated the importance of
Natural Selection AND Genetic Drift
But they argued about the relative
importance
Ronald Aylmer Fisher (1890-1962)
Background in math,
physics, astronomy, and
genetics
Made key contributions
to the field of Statistics
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)
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
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
The Population
Geneticists
If you want to read more about this
topic, this book is a good read
Reconciling Microevolutionary Mechanisms
and Macroevolutionary processes
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 (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)
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
The Importance of Natural Selection vs Genetic Drift
Ongoing debate after the Evolutionary Synthesis
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
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.
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.
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)
Some Tenets of the Evolutionary Synthesis
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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
Completing the Synthesis
Advances in Genetics
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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
Evolution at the Molecular Genetic Level
Which types of mutations predominate and contribute to
adaptations more often?
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Structural vs Regulatory?
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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?
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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)
The role of Epigenetics
(Lecture #9)
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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
Evolution of
Development
(Lecture #26)
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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
Role of Genomics
(Lectures #15, 16)
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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?
Today: Genome Evolution and Systems Biology
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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
Questions:
(1) What were the sources of confusion regarding evolutionary
mechanisms prior 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?
Moral of the Story
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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)
Sample Exam Question
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
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Answer: d