Dr. Carol Eunmi LeeUniversity of Wisconsin, Madison

HistoryHistory of of Evolutionary Thought:Evolutionary Thought:

The Grand Evolutionary The Grand Evolutionary SynthesisSynthesis

(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

Today’s OUTLINE:

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”

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

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

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)

Mendel’s work held part of the key to what was missing in Darwin’s Theory

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”

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

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?

Selection vs Mutations

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 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

Frequency

Type

Type

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 Darwinist 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

Proponents of the Mutationist/Mendelist Theory

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:

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: 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

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

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

The Modern SynthesisThe Modern Synthesis1930s ~ 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 SynthesisThe Modern Synthesis1930s ~ 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

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 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 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

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

JBS Haldane

Sewall Wright

RA Fisher

The Population Geneticists

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.

Fisher vs WrightBoth appreciated the importance of Natural Selection AND Genetic DriftBut they argued about the relative importance

Background in math, physics, astronomy, and genetics

Made key contributions to the field of Statistics

Ronald Aylmer Fisher (1890-1962)

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)

Ronald Aylmer Fisher (1890-1962)• Natural selection occurs in large populations

• Many genes are involved

• Mutations are the main substrate for selection

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

Sewall Wright (1889-1988)

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

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)

Ernst Mayr

Ernst MayrGeorge Gaylord SimpsonG. Ledyard StebbinsBernhard Renschand others

George Gaylord Simpson

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

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

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)

• 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.

Motoo Kimura

• 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.

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 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

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

Advances in Genetics

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 (Lecture #13)

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

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

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?

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

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

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

Answer: d