Natural Selection Outline

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Natural Selection Outline

• Introduction what is natural selection?
• Stabilizing selection
• Genetic variation for fitness
• Estimation of fitness
• Interplay of forces on genetic variation

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Natural Selection Outline

• Introduction what is natural selection?
• Stabilizing selection
• Genetic variation for fitness
• Estimation of fitness
• Interplay of forces on genetic variation

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Natural selection has two outcomes

• Stasis
• Change

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Natural selection is a systematic change in
allele frequency

• Dq q1 - q
• s is the strength of selection

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Detecting selection in nature

• manipulation of populations or of individuals
• estimating selection coefficients change in
  gene frequency from parents to offspring, among
  cohorts, etc.
• the comparative method traits in unrelated
  species living in similar habitats
• association of gene frequencies with selective
  agent across a gradient in either space or time
• selection history can be read in the sequence of
  the gene

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Fitness profile

• A fitness profile is a plot of fitness against
  phenotypic value, expressed as standard
  deviations from the means.
• Dotted line fitness
• (1) directional selection for high values major
  component of fitness
• (2) stabilizing selection intermediate optimum
• (3) very weak selection nearly neutral

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Neutral characters

• Test for neutrality by perturbation test
  artificially select away from mean, then relax
  selection. If character is neutral, it will not
  return to its previous value
• May not work if allele frequencies greatly
  altered, inbreeding occurs, etc.

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Natural Selection Outline

• Introduction what is natural selection?
• Stabilizing selection
• Genetic variation for fitness
• Estimation of fitness
• Interplay of forces on genetic variation

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Intermediate optima causes

• Real stabilizing selection there is a causal
  relationship between the trait and fitness, and
  the optimum phenotype is intermediate
• Apparent stabilizing selection genes affecting
  trait have pleiotropic effect on fitness
  components

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Apparent stabilizing selection I

• If individuals with extreme phenotypes are less
  fit because they have more deleterious mutations
• If mutations with large effects on the trait also
  have large effects on fitness

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Apparent stabilizing selection II

• Example clutch size in birds. Bigger clutches
  yield more offspring, but require less well
  provisioned eggs which yield lower quality
  offspring
• Negative genetic correlations between fertility
  and viability could result in intermediate
  optimum for trait

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Natural Selection Outline

• Introduction what is natural selection?
• Stabilizing selection
• Genetic variation for fitness
• Estimation of fitness
• Interplay of forces on genetic variation

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Genetic variation for fitness

• Roff and Mousseau surveyed heritabilities in a
  variety of species and found moderate to high
  heritabilities for quantitative traits
• Life history traits tend to have lower
  heritabilities than morphological traits,
  probably because they are more closely related to
  fitness

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Natural selection operates on fitness

• Fitness is the target of natural selection
• Fitness is the individuals contribution of
  offspring (alleles) to the next generation
• Different metric traits contribute different
  amounts to fitness, and can be arranged in a
  hierarchy reflecting the extent of the traits
  contribution

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Hierarchy of traits contributing to fitness
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Relative fitness

• The fitness of an individual relative to the
  population mean is its relative fitness.
• E.g., contributing 100 offspring sounds good
  unless an average individual in the population
  contributes 200!
• Relative fitness

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Fitness of a population
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Fitness includes the environment

• Fitness includes not just the genes but the
  environment
• The fitness of a gene is defined by the
  environment in which it is found
• Part of the environment is genetic (i.e. the
  organisms interacting with the focal individual),
  and thus the environment can also evolve

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Major components of fitness I

• Constant selection reduces VA, thus causing low
  h2, because VE remains high
• Directional dominance causes VNA, thus we have
  inbreeding depression

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Major components of fitness II

• Tend to observe negative genetic correlations
  between major components of fitness in random
  mating populations ( tradeoffs, antagonistic
  pleiotropy)
• Economic/budget models a total amount of
  resources exists, must be divided among multiple
  components, thus cant maximize all components
  simultaneously
• QG model any pleiotropic alleles that affect
  multiple components of fitness favorably will be
  fixed quickly, eliminating VG. Genes with
  antagonistic pleiotropy remain at intermediate
  frequencies.

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Major components of fitness III

• Thus expect positive genetic correlation between
  fitness components in inbred lines, because
  deleterious recessive homozygotes are likely
  pleiotropic with respect to fitness components

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Fishers fundamental theorem

• Increase in fitness at any given time equals the
  additive genetic variance of fitness at that time
• Recall R h2S weve already established in
  order to have a response to selection, we must
  have non-zero h2

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Stable populations

• A stable population, that is neither growing nor
  shrinking, has a mean fitness of 1
• In a stable population, absolute and relative
  fitness are the same
• We can still see evolution in a stable population
  as increasing absolute fitness (nonzero Dq), but
  mean fitness remains 1.

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Equilibrium populations I

• If action of natural selection is constant (i.e.
  environment does not change, no mutation or
  migration), eventually an equilibrium is reached
  with Dq 0
• Thus is zero, so response to selection is
  zero (Fishers FT) even though selection is still
  operating

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Equilibrium populations II

• However, this does not mean VG 0, just that VG
  is non-additive
• Overdominant genes at intermediate frequencies
• In an equilibrium population, allele frequencies
  maximize fitness by definition
• Thus selection on a non-fitness trait reduces
  fitness by changing allele frequencies, unless
  the trait is neutral and unlinked to fitness loci

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Natural Selection Outline

• Introduction what is natural selection?
• Stabilizing selection
• Genetic variation for fitness
• Estimation of fitness
• Interplay of forces on genetic variation

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Fitness is hard to estimate I

• Because it is the ultimate complex trait
• Because separating parent fitness from offspring
  fitness is difficult (if a good parent mates with
  a poor parent, the good parents fitness is not
  represented exactly in its offspring)
• Because measuring fitness of individuals is
  difficult, and thus fitness must be extrapolated
  from multiple individuals

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Fitness is hard to estimate II

• Because measuring total fitness is very difficult
  even in the lab, so fitness is often extrapolated
  from multiple fitness components
• Because the variance in fitness is very large,
  due to the large contribution of the environment

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Strength of natural selection

• Can measure in two ways, depending on traits
  relationship to fitness
• Major fitness components are under directional
  selection
• Characters with intermediate optima are under
  stabilizing selection

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Correlated responses

• Response of a character correlated with fitness
  to selection on fitness itself is the additive
  covariance of character Y with fitness
• Estimating those parameters is nontrivial!

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Directional selection I

• Linear regression of fitness on trait is
• is the correlated selection differential for the
  character
• is the selection gradient, or, the partial
  regression coefficient for each of many characters

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Directional selection II

• Standardize across organisms or environments by
  dividing by the phenotypic standard deviation of
  the trait
• I tells us the intensity of selection, but does
  not predict the actual changes natural selection
  will make in the trait

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Stabilizing selection

• Traits with intermediate optima are under
  stabilizing selection alternatively, traits
  where extremes are deleterious
• is the strength of selection if stabilizing
  selection, j is negative if disruptive
  selection, j is positive
• is the variance before selection
• is the variance in the same generation after
  selection

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Estimation of relative fitness

• Depends on competitive measures, such that the
  competitor is standard between genotypes/treatment
  s and thus is an internal control

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Natural Selection Outline

• Introduction what is natural selection?
• Stabilizing selection
• Genetic variation for fitness
• Estimation of fitness
• Interplay of forces on genetic variation

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Forces affecting quantitative variation

• Selection
• Genetic drift
• Mutation
• Migration

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Genetic drift

• Loss of genetic variation at rate governed by
  effective population size Ne
• In the absence of mutation and migration, drift
  will eventually extinguish all genetic variation

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Mutation

• Mutation is the ultimate source of new genetic
  variation
• The range of input per generation is denoted by
  VM. Estimates for VM for Drosophila bristle
  traits are consistently in the range of 10-3 VE

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Mutation and drift interact I

• Incorporating variance loss from drift with input
  from mutation
• In terms of heritability
• So for VM 10-3 VE,
• h2 0.002 Ne/(1 0.002 Ne)

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Mutation and drift interact II

• Thus mutation in the absence of selection can
  maintain a large amount of variation, except in
  very small populations
• Heritabilities of most characters are much lower
  than predicted by the neutral model, so for most
  characters, selection must reduce VG

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Joint action of mutation, directional selection,
and drift I

• Assumptions
• Mutations affect fitness only via effects on the
  trait
• Additivity
• Equilibrium response and variance are independent
  of the absolute magnitude of mutant effects, but
  depend on P, the proportion of favorable
  mutations

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Joint action of mutation, directional selection,
and drift II

• If mutations are equally likely to be positive or
  negative, i.e. P 0.5, then the equilibrium
  variance under this model is the same as the
  mutation-drift model

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Joint action of mutation, directional selection,
and drift IV

• Only advantageous mutations contribute
  appreciably to variation and response, and do so
  during their sweep to fixation
• This model predicts the maintenance of large
  amounts of variation

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Heterozygote superiority models for maintenance

• Pure overdominance
• Pleiotropic overdominance
• Marginal overdominance

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Pure overdominance model

• Stable equilibrium at q s1 / (s1 s2)
• However, few examples are known

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Pleiotropic overdominance model

• There is some evidence of antagonistic pleiotropy
  for major fitness components

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Marginal overdominance model

• Relative fitness changes according to
  environmental change, temporal or spatial
• Different homozygous genotypes are favored in
  different environments, leading to heterozygote
  superiority when averaged across environments

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Stabilizing selection

• The most intensively studied model
• Effect of stabilizing selection is to eliminate
  genetic variation
• New mutations are unconditionally deleterious and
  independent

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Multiple loci under stabilizing selection I

• VG 4nmVS, such that n is the number of loci and
  m is the per locus mutation rate
• Assume that VS 10 VE (strong stabilizing
  selection) and h2 0.5
• Predicts that nm 2.5 x 10-2

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Multiple loci under stabilizing selection II

• Thus, for appreciable heritabilities, either n or
  m must be large
• If n 100, m 2.5 x 10-4, which is too high
• If m 10-5, n 2500, which seems too high,
  unless a large fraction of the genome affects a
  given trait
• However, recent surveys suggest stabilizing
  selection may be weak (Kingsolver et al. 2001)

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Problems with stabilizing selection model

• Seems to predict high h2 only with strong
  selection, if a large number of loci affect the
  trait
• If each trait is affected by many loci, traits
  cannot be considered independent
• If there really are large numbers of independent
  traits, the genetic load is too high, that is,
  too many individuals will fail to reproduce for
  genetic reasons

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Pleiotropic model I

• Apparent stabilizing selection can occur if
  mutations have deleterious pleiotropic effects on
  fitness
• Mutations with large effects on the trait may
  also have large effects on fitness
• Thus individuals with extreme phenotypes are less
  fit because they have more deleterious mutations

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Pleiotropic model II

• Assumptions
• Equally deleterious mutations with heterozygous
  fitness 1 - s
• Selection is strong relative to mutation

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Pleiotropic model III

• Given VG VM /s, where s is the strength of
  selection,
• Assuming s 0.05 and
• VG/VE VM /(0.05 VE),
• Then VM/VE 0.05

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Pleiotropic model IV

• VM/VE 0.05 is higher than observed
• Alternatively, high levels of VG can be explained
  with this model if individual mutations have very
  small effects, but this only generates weak
  stabilizing selection

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Conclusions on maintenance

• The maintenance of quantitative genetic variation
  remains an unsolved problem
• Information on the nature of segregating
  variants, via QTL mapping, may help
• Empirical data on pleiotropy of mutations
  affecting quantitative traits would also be
  useful!