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Mutationism, Mutationism, Neutralism, Neutralism, SelectionismSelectionism

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Deleterious mutations

Advantageous mutations

Neutral mutations

Overdominant mutations

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New mutations may be:New mutations may be:1. Advantageous1. Advantageous2. Overdominant2. Overdominant3. Deleterious3. Deleterious4. Neutral4. Neutral

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Probability of fixation:Probability of fixation:1. Advantageous - 1. Advantageous - lowlow2. Overdominant – 2. Overdominant –

close to close to zerozero (genetic (genetic load)load)

3. Deleterious - very 3. Deleterious - very very very lowlow

4. Neutral - very 4. Neutral - very lowlow

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Conditional time to Conditional time to fixation:fixation:

1. Advantageous - 1. Advantageous - fastfast

2. Overdominant - 2. Overdominant - extremely slowextremely slow

3. Deleterious - fast3. Deleterious - fast4. Neutral - slow4. Neutral - slow

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Deleterious mutations

Advantageous mutations

Neutral mutations

Overdominant mutations

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Amount of variability Amount of variability created:created:

1. Advantageous - 1. Advantageous - nonenone

2. Overdominant - a 2. Overdominant - a lotlot

3. Deleterious - none3. Deleterious - none4. Neutral - some4. Neutral - some

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THE DRIVING FORCES IN EVOLUTION

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3 types of evolutionary explanations:

•Mutationism = evolutionary phenomena are explained by the joint effects of mutational input and random genetic drift.

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•Neutralism = evolutionary phenomena are explained by the joints effects of mutation, random genetic drift, and purifying selection.

3 types of evolutionary explanations:

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•Selectionism = evolutionary phenomena are explained by the joints effects of advantageous selection and balancing selection.

3 types of evolutionary explanations:

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Selectionism

• Gene substitutions occur as a consequence of selection for advantageous mutations. Polymorphism is maintained by balancing selection.

• Gene substitution and polymorphism are two separate phenomena driven by different evolutionary forces.

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Gene substitution is the end result of an adaptive process whereby a new allele takes over future generations of the population if and only if it improves the fitness of the organism.

Polymorphism is maintained when the coexistence of two or more alleles at a locus is advantageous for the organism or the population.

Selectionism

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•Two separate evolutionary forces!

•Genetic polymorphism is permanent - the same alleles are maintained at constant frequencies for long periods of evolutionary time.

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AdaptationAn adaptation is a heritable character state that enhances the fitness of the organisms that bear it relative to alternative character states, especially ancestral character states in the population in which the adaptation evolved.

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Honey creepersHoney creepers

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AdaptationTranslation into Molecular Lingo:

An adaptation is a mutation that enhances the fitness of the organisms that carry it relative to the other alleles in the population.

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Extreme selectionism leads to The “Panglossian paradigm”

“It is proved… that things cannot be other than they are, for since everything was made for a purpose, it follows that everything is made for the best purpose.”

Dr. Pangloss in Dr. Pangloss in CandideCandide by Voltaire by Voltaire

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The Panglossian paradigm:

“Observe, for instance, the nose is formed for spectacles, therefore we wear spectacles.”

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The Panglossian paradigm:

“Legs were clearly intended for breeches , and we wear them.”

Dr. Pangloss in Dr. Pangloss in CandideCandide by Voltaire by Voltaire

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Abbott Handerson ThayerAbbott Handerson Thayer1849-19211849-1921

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1911

1901–1909: President of the United States. 1911: A 116-page article on animal coloration.

27Motoo Kimura

The Neutral Theory of Molecular Evolution

Kimura M. 1968. Evolutionary rate at the molecular level". Nature 217: 624–626. King JL, Jukes TH. 1969. Non-Darwinian Evolution. Science 164: 788–798.

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The majority of evolutionary changes and much of the variability within species are caused by random genetic drift of mutant alleles that are selectively neutral or nearly so.

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Neutrality, in the sense of the neutral theory, does not imply strict equality in fitness for all alleles. It only means that the fate of alleles is determined largely by random genetic drift.

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Selection may operate, but its intensity is too weak to offset the influences of chance effects. s< 1/(2Ne) Ne = effective

population size.

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That is, either the selection coefficient is small, or the effective population size is small. s< 1/(2Ne) Ne = effective

population size.

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According to the neutral theory, the frequency of alleles is determined by purely stochastic rules, and the picture that we obtain at any given time is merely a transient state representing a temporary frame from an ongoing dynamic process.

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The neutral theory regards substitution and polymorphism as two facets of the same phenomenon.

Gene substitution is a long and gradual process whereby the frequencies of mutant alleles increase or decrease randomly, until the alleles are ultimately fixed or lost by chance.

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Polymorphic loci consist of alleles that are either on their way to fixation or are about to become extinct. Thus, at any given time, some loci will possess alleles at frequencies that are neither 0% nor 100%. These are the polymorphic loci.

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All molecular manifestations that are relevant to the evolutionary process should be regarded as the result of a continuous process of mutational input and a concomitant random extinction or fixation of alleles.

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•A single evolutionary force.

•Genetic polymorphism is transient - allele frequencies fluctuate with time and the polymorphic alleles themselves are continuously replaced.

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A population that is free from selection can accumulate many polymorphic neutral alleles. Then, if a change in ecological circumstances occurs, some of the neutral alleles will no longer be neutral but deleterious, against which purifying selection may operate. After these alleles are removed, the population will become more adapted to its new circumstances than before.

Kimura (1983)

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The neutral theory does not preclude

adaptation.

Adaptive evolution may occur without adaptive

selection.

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The SliSligghtlhtlyy Deleterious Model of Molecular Evolution +The SliSligghtlhtlyy Advantageous Model of Molecular Evolution = The Nearly Neutral Model of Evolution

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Mean

fitness

time

selectionism

neutralism

nearly neutral model

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Leigh Van Valen’s “Red Queen Hypothesis” (based “Through the Looking-Glass, and What Alice Found There” by Lewis Carroll (1871).

Alice complains to the Red Queen that she is exhausted from running, only to find she is still under the tree where she started. The Red Queen replies:

“Now, here, you see, it takes all the running you can do to keep in the same place. If you want to get somewhere else, you must run at least twice as fast as that.”

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Neutralist-selectionist Neutralist-selectionist perceptionsperceptions

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A total resolution of the dispute between neutralists and selectionists would require knowledge of the distribution of fitness effects of mutant alleles.

Neutralist-selectionist Neutralist-selectionist perceptionsperceptions

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The distribution of fitness effects of random mutations in vesicular stomatitis virus. Random mutations were introduced into the virus, and the fitnesses of the mutants were compared against the unmutated wild type. A fitness of less than one indicates that the mutant was less fit than the wild type, so the mutation was deleterious. A fitness of zero indicates that no mutated progeny were recovered, and that the mutation was therefore lethal.From: Eyre-Walker A, Keightley PD. 2007. The distribution of fitness effects of new mutations. Nature Rev. Genet. 8:610-618.

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Yeast

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Fact 1:

The cheetah is about to become extinct.

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Fact 2:

Cheetah populations are devoid of genetic variation.

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1. Selectionist explanation:

The cheetahs are depauperate of genetic variation and, therefore, they are on the verge of extinction.

Two explanations:

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2. Neutralist explanation:

The cheetahs are on the verge of extinction and, therefore, they are depauperate of genetic variation.

Two explanations:

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If genetic variation reflects adaptive needs, then advantageous selection will quickly restore genetic variability to its pre-bottleneck levels.

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If genetic variation is merely random sampling, then post-bottleneck genetic variability will remain low for very long periods.

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Northern elephant seal, Mirounga angustirostris1922, Baja California, ~20 animals2000, Baja California, ~120,000 animalsGenetic variation = ~ 0

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Helix aspersa (brown garden snail)

Europe

California

H = 0.121

few individuals

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Helix aspersa (brown garden snail)

Europe

CaliforniaH = 0.000

H = 0.121

Large populations.Important pests of citrus trees.

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Neutrality tests(no need to know history)

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polymorphic fixed

synonymous X Y

nonsynonymous

Z W

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Type of change

Fixed

Polymorphic

Synonymous 26 36

Nonsynonymous

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Numbers of synonymous and nonsynonymous fixed differences and polymorphisms at the glucose-6-phosphate dehydrogenase locus between Drosophila melanogaster and D. simulans

The comparisons are based on 32 sequences from D. melanogaster and 12 sequences from D. simulans, with an aligned length of 1,705 bp.

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polymorphic fixed

synonymous X Y

nonsynonymous

Z W