What is evolution

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What is evolution?
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Evolution A process of change in a certain
direction. A process of gradual and peaceful
advance. The historical development of a
biological group. A theory that the various types
of animals and plants have their origin in other
preexisting types and that the distinguishable
differences are due to modifications in
successive generations.
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Evolution A change in the composition of the
gene pool.
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Possible Changes 1. allele frequencies 2.
genotype frequencies
1.
2.
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1. Changes in allele frequencies are
important. 2. Changes in genotype frequencies are
not so important.
Selection Random genetic drift
1.
2.
Deviations from random mating Migration
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Deviation from random mating By genetic
similarity Assortative mating Disassortative
mating By genetic relatedness Inbreeding Out
breeding
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disassortative
assortative
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Inbreeding
Cousins are preferred mates in many human
cultures.
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The fish Rivulus marmoratus exhibits the most
extreme form of inbreeding Selfing
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Even if extreme deviations from random mating
occur in all generations, allele frequencies
remain constant.
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Selection
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Selection The differential reproduction of
genetically distinct individuals (genotypes)
within a population. Differential reproduction
is caused by differences among individuals in
such traits as (1) mortality, (2) fertility
(offspring), (3) fecundity (gametes), (4) mating
success, and (5) viability of offspring.
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Natural selection is predicated on the
availability of genetic variation among
individuals in characters related to reproductive
success (variation in fitness).
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Variability
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Arashnia levana Non-genetic variability.
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Helix aspersa Genetic variability.
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Variability
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Genetic? Fitness related?
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Synonymous and nonsynonymous genetic variability.
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The fitness (w) of a genotype is a measure of the
individuals ability to survive and reproduce.
The size of a population is constrained by the
carrying capacity of the environment. Thus, an
individuals evolutionary success is determined
not by its absolute fitness, but by its relative
fitness in comparison to the other genotypes in
the population.
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For simplicity

• We assume that fitness is determined solely by
  the genetic makeup.
• We assume that all loci contribute independently
  to fitness (i.e., the different loci do not
  interact with one another in a manner that
  affects fitness), so that each locus can be dealt
  with separately.

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A very simple model (1) One locus A Two
alleles A1 A2 The old allele A1 The new
allele is A2 Three genotypes A1A1, A1A2
A2A2 Each genotype has a typical fitness (w) We
are interested in the fate of A2
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A very simple model (2) The fitness of the old
genotype (A1A1) is set at 1. The relative
fitnesses of the two new possible genotypes (A1A2
A2A2) are defined comparatively as 1 s or 1
t, where s and t are the selection coefficients.
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Genotype A1A1 A1A2 A2A2 Fitness
w11 w12 w22 Frequency p2 2pq q2
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Change in A2 allele frequency per generation
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Genotype A1A1 A1A2 A2A2 Fitness
w11 w12 w22 Frequency p2 2pq q2
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codominance
Genotype A1A1 A1A2 A2A2 Fitness 1 1 s 1 2s
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A1 dominance
Genotype A1A1 A1A2 A2A2 Fitness 1 1 1 s
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A2 dominance
codominance
Genotype A1A1 A1A2 A2A2 Fitness 1 1 s 1 s
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Directional Selection
codominance
A2 dominance
A1 dominance
A1 old mutant A2 new mutant
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Tay-Sachs is a recessive allele
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Selection against recessive lethal alleles
b-hexosaminidase A is a lysosomal. It is encoded
by a gene on chromosome 15.
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Selection against recessive lethal alleles
b-hexosaminidase-A catalyzes the removal of
N-acetylgalactosamine from GM2 ganglioside,
thereby degrading and removing it from the
nervous system.
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Selection against recessive lethal alleles
Absence of b-hexosaminidase-A
? Accumulation of GM2 ganglioside in neurons.
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Tay-Sachs is a recessive lethal alleles
Symptoms of classical Tay-Sachs disease first
appear at 4 to 6 months of age when an apparently
healthy baby gradually stops smiling, crawling or
turning over, loses its ability to grasp or reach
out and, eventually, becomes blind, paralyzed and
unaware of its surroundings. Death occurs by age
3-5.
Cherry-red spot from an infant with Tay-Sachs
disease.
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Selection against recessive lethal alleles
allele frequency
recessive allele
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Inefficiency of selection against recessive allele
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It is difficult to rid a population of recessive
alleles, because they hide behind the back of
dominant alleles, and are not exposed to
selection. If q 50, then 50 of all recessive
alleles are in heterozygous state and 50 are
subject to selection. If q 10, then 98 of
all recessive alleles are in heterozygous state
and 2 are subject to selection. If q 1, then
99.98 of all recessive alleles are in
heterozygous state and 0.02 are subject to
selection.
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Selection against dominant lethal alleles
Dr. George Sumner Huntington 1850-1916
Protein huntingtin Gene 180 Kb (chromosome
4) Exons 67 Amino acids 3,141 Mode autosomal
dominant
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Selection against dominant lethal alleles
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It should be easy to rid a population of dominant
alleles, because all of them are exposed to
selection at all frequencies. So why are there
dominant lethal diseases?
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1. Recurrent mutations.
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2. Late age of onset.
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Balancing Selection
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Overdominance
codominance
Genotype A1A1 A1A2 A2A2 Fitness 1 1 s 1
t s gt 0 s gt t Depending on whether the fitness
of A2A2 is higher than, equal to, or lower than
that of A1A1, t can be positive, zero, or
negative, respectively.
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The change in the frequency of A2 from generation
to generation is
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At equilibrium, i.e., when ?q 0.
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overdominance
underdominance
s 0.04 and t 0.02
s - 0.02 and t - 0.01
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Overdominant selection is inherently inefficient,
even if the two homozygotes are not viable.
RIP
Powderpuff
Chinese Crested
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Random Genetic Drift
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Drift
Allele frequency changes can occur by chance, in
which case the changes are not directional but
random. An important factor in producing
changes in allele frequencies is the random
sampling of gametes during reproduction.
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Niche capacity 10 plants
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• A simple idealized model
• All the individuals in the population have
  the same fitness (selection does not operate).
• The generations are nonoverlapping.
• Adult population size is finite does not
  change from generation to generation.
• Gamete population size is infinite.
• The population is diploid (N individuals, 2N
  alleles).
• One locus with two alleles, A1 and A2, with
  frequencies p and q 1 p, respectively.

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When 2N gametes are sampled from the infinite
gamete pool, the probability, Pi, that the sample
contains exactly i alleles of type A1 is given by
the binomial probability function
Since Pi is always greater than 0 for populations
in which the two alleles coexist (i.e., 0 lt p lt
1), the allele frequencies may change from
generation to generation without the aid of
selection.
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The process of change in allele frequency due
solely to chance effects is called random genetic
drift.
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Fixation
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Magnitude of fluctuations depends on population
size. Large population Small fluctuations.
Small population Large fluctuations. Mean
time to fixation or loss depends on population
size. Large population Long time. Small
population Short time.
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yet
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In mathematical terms, the mean and variance of
the frequency of allele A1 at generation t are
given by Expected mean frequency does not
change with time variance increases with time.
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With each passing generation the allele
frequencies will tend to deviate further and
further from their initial values, however the
change in allele frequencies will not be
systematic in its direction.
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Change in probability of not deviating from
initial frequencies with time
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Effective population size
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Population size the total number of individuals
in a population. From an evolutionary point of
view, however, the relevant size consists of only
those individuals that actively participate in
the reproductive process. This part is called
the effective population size and is denoted by
Ne.
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Why isnt the census size satisfactory?
Some individuals may contribute little to the
reproductive potential of a population
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Sewall Wright (1931) introduced the concept of
effective population size, which he rigorously
defined as the size of an idealized population
that would have the same effect of random
sampling on allele frequencies as that of the
actual population.
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Assume a population with census size N and
frequency of allele A1 at generation t p. If
the number of individuals taking part in
reproduction N, then the variance of the
frequency of allele A1 in the next generation,
pt1, may be obtained from the variance equation
by setting t 1.
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Gene Substitution
Gene substitution is the process whereby a mutant
allele completely replaces the predominant or
wild type allele in a population. Gene
substitution occurs when a mutant allele arises
in a population as a single copy and, then,
increases its frequency to 1 (i.e., becomes
fixed) after a certain number of generations.
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Not all mutants, however, reach fixation. In
fact, the majority of them are lost after a few
generations.
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For a neutral mutation, i.e., s 0 For
positive values of s and large values of
N
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Thus, if an advantageous mutation arises in a
large population and its selective advantage over
the rest of the alleles is small (up to 5),
then the fixation probability is approximately
twice its selective advantage. For example, the
probability of fixation of a new codominant
mutation with s 0.01 is 2. Out of all
advantageous mutations with a selective advantage
of 1, 98 will be lost.
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Probabilities of Fixation
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Conditional Fixation Time In the case of a new
neutral mutation whose initial frequency in a
diploid population is by definition q 1/(2N),
the mean conditional fixation time is
approximated by For a mutation with a
selective advantage of s, the mean conditional
fixation time is approximated by
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Conditional Fixation Times
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Rate of Gene (or Allele) Substitution number
of mutants reaching fixation per unit time
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Rate of Gene Substitution Neutral mutations
If neutral mutations occur at a rate of u per
gene per generation, then the number of mutants
arising at a locus in a diploid population of
size N is 2Nu per generation. The probability
of fixation for each neutral mutation is 1/(2N).
The rate of substitution of neutral alleles is
obtained by multiplying the total number of
mutations by the probability of their fixation.
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Intuitive explanation In a large population the
number of mutations arising in every generation
is high, but the fixation probability of each
mutation is low. In a small population the
number of mutations arising in every generation
is low, but the fixation probability of each
mutation is high. The rate of substitution for
neutral mutations is independent of population
size.
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Rate of Gene Substitution Advantageous
mutations If advantageous mutations occur at a
rate of u per gene per generation, then the
number of mutants arising at a locus in a diploid
population of size N is 2Nu per generation. The
probability of fixation for each mutation is
2s. The rate of substitution of advantageous
alleles is 4Nsu.
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Deleterious mutations
Neutral mutations
Overdominant mutations
Advantageous mutations
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New mutations may be 1. Advantageous 2.
Overdominant 3. Deleterious 4. Neutral
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Probability of fixation 1. Advantageous -
low 2. Overdominant close to zero (genetic
load) 3. Deleterious - very very low 4. Neutral
- very low
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Conditional time to fixation 1. Advantageous -
fast 2. Overdominant - extremely slow 3.
Deleterious - fast 4. Neutral - slow
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Amount of variability created 1. Advantageous -
none 2. Overdominant - a lot 3. Deleterious -
none 4. Neutral - some
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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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3 types of evolutionary explanations

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

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3 types of evolutionary explanations

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

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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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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
Candide 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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Abbott Handerson Thayer 1849-1921
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Neutralism, or The Neutral Theory of Molecular
Evolution
Motoo Kimura
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The Neutral Theory of Evolution (Neutralism)
considers mutation, random genetic drift, and
purifying selection to be the main driving forces
of the evolutionary process.
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The neutral theory of molecular evolution
contends that at the molecular level 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?lt 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 neutralist-selectionistdebate
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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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Two explanations
1. Selectionist explanation The cheetahs lack
genetic variation and, therefore, they are on the
verge of extinction.
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Two explanations
2. Neutralist explanation The cheetahs are on
the verge of extinction and, therefore, they lack
genetic variation.
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1922, Baja California, 20 animals 2000, Baja
California, 120,000 animals Genetic variation
0
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Helix aspersa (brown garden snail)
H 0.121
Europe
1850
California
few individuals
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Helix aspersa (brown garden snail)
H 0.121
Europe
1990
California
Large populations. Important pests of citrus
trees.
H 0.000
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Neutrality tests
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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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The essence of the dispute between neutralists
and selectionists basically concerns the
distribution of fitness values of mutant alleles.
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Both theories agree that most new mutations are
deleterious, and that these mutations are quickly
removed from the population so that they
contribute neither to the rate of substitution
nor to the amount of polymorphism within
populations.
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The difference concerns the relative proportion
of neutral mutations among nondeleterious
mutations. While selectionists claim that very
few nondeleterious mutations are selectively
neutral, neutralists maintain that the vast
majority of nondeleterious mutations are
effectively neutral.
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Detecting Positive Darwinian Selection
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Deleterious mutations
Neutral mutations
synonymous
Overdominant mutations
Advantageous mutations
nonsynonymous
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Prevalence of positive selection
In humans, estimates of the prevalence of
positive selection in protein-coding genes range
from 0.02 to 8.7 (a 435-fold range). In other
words, 91.30 to 99.98 of all genes evolve in a
neutral fashion.
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Codon Usage
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Codon-usage bias
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Measures of codon-usage bias
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The relative synonymous codon usage (RSCU) is the
number of times a codon appears in a gene divided
by the number of expected occurrences under equal
codon usage. n number of synonymous codons
(1 ? n ? 6) for the amino acid under study, Xi
number of occurrences of codon i. If the
synonymous codons of an amino acid are used with
equal frequencies, their RSCU values will equal
1.
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The codon adaptation index (CAI) measures the
degree with which genes use preferred codons.
We first compile a table of RSCU values for
highly expressed genes. From this table, it is
possible to identify the codons that are most
frequently used for each amino acid. The relative
adaptiveness of a codon (wi) is computed
as where RSCUmax the RSCU value for the
most frequently used codon for an amino acid.
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The CAI value for a gene is calculated as the
geometric mean of wi values for all the codons
used in that gene. where L number of
codons.
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The effective number of codons (ENC) where Fi
(i 2, 3, 4, or 6) is the average probability
that two randomly chosen codons for an amino acid
with i codons will be identical. ENC values
range from 20 (the number of amino acids), which
means that the bias is at a maximum, and only one
codon is used from each synonymous-codon group,
to 61 (the number of sense codons), which
indicates no codon-usage bias.
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Universal and species-specific patterns of codon
usage
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The genome hypothesis All genes in a genome
tend to have the same coding strategy. That is,
they employ the codon catalog similarly and show
similar choices between synonymous codons.
Different taxa have different coding
strategies.
Richard Grantham
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Universal patterns Codons that contain the CG
dinucleotide are universally avoided (low-usage
codons). This phenomenon is particularly notable
as far as the arginine codons CGA and CGG are
concerned.
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Codon Usage is related to Translation Efficiency
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The translation efficiency of a codon is related
to the relative quantity of tRNA molecules that
recognize the particular codon.
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Codon Usage is related to Translation Efficiency
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Toshimishi Ikemura
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Rules determining choice of optimal codons in
unicellular organisms ____________________________
______ 1. tRNA availability. 2. Preference
for A over G when thiolated uridine or
5-carboxymethyl are at the anticodon wobble
position. 3. Preference for T and C over A
when inosine is at the anticodon wobble
position. 4. Codons of the AAN, ATN, TAN, and
TTN type prefer C in the third codon
position. __________________________________
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Codon usage in multicellular organisms
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Subramanian S. 2008. Genetics 1782429-2432