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Deviations from HWE
I. Mutation
II. Migration
III. Non-Random Mating
IV. Genetic Drift
V. The Neutral Theory
Deviations from HWE
I. Mutation
II. Migration
III. Non-Random Mating
IV. Genetic Drift
V. The Neutral Theory
A. Variation
1. Phenotypic variation was often interpreted as having selective
value; in fact, most studies confirmed that under one environmental
condition or another, there was a difference in fitness among variations. Mayr
(1963) "it is altogether unlikely that two genes would have identical selective
value under all conditions under which they may coexist in a population.
Cases of neutral polymorphism do not exist."
Deviations from HWE
I. Mutation
CCC = Proline
II. Migration
CCU = Proline
CCA = Proline
III. Non-Random Mating
CCG = Proline
IV. Genetic Drift
V. The Neutral Theory
A. Variation
1. Phenotypic variation was often interpreted as having selective
value; in fact, most studies confirmed that under one environmental
condition or another, there was a difference in fitness among variations. Mayr
(1963) "it is altogether unlikely that two genes would have identical selective
value under all conditions under which they may coexist in a population.
Cases of neutral polymorphism do not exist."
2. In the 1960's - lots of electrophoretic work revealed a vast amount
of variability - variability at the gene or protein level that did not necessarily
correlate with morphological variation. Some are silent mutations in DNA, or
even neutral substitution mutations. This variation results in heterozygosity.
Deviations from HWE
I. Mutation
II. Migration
III. Non-Random Mating
IV. Genetic Drift
V. The Neutral Theory
A. Variation
3. Most populations showed mean heterozygosities across ALL loci
of about 10%.
- And, about 20-30% of all loci are polymorphic (have at least 2
alleles with frequencies over 1%).
Drosophila has 10,000 loci, so 3000 are polymorphic.
At these polymorphic loci, H = .33
Conclusion - lots of variation at a genetic level... is this also solely
maintained by selection?
Deviations from HWE
I. Mutation
II. Migration
III. Non-Random Mating
IV. Genetic Drift
V. The Neutral Theory
A. Variation
B. Genetic Load
Deviations from HWE
I. Mutation
II. Migration
III. Non-Random Mating
IV. Genetic Drift
V. The Neutral Theory
A. Variation
B. Genetic Load
1. "HARD" Selection can 'cost' a population individuals:
Deviations from HWE
I. Mutation
II. Migration
III. Non-Random Mating
IV. Genetic Drift
V. The Neutral Theory
A. Variation
B. Genetic Load
1. "HARD" Selection can 'cost' a population individuals:
- those that die as a consequence of differential fitness values.
Deviations from HWE
I. Mutation
II. Migration
III. Non-Random Mating
IV. Genetic Drift
V. The Neutral Theory
A. Variation
B. Genetic Load
1. "HARD" Selection can 'cost' a population individuals:
- those that die as a consequence of differential fitness values.
- the "breeding population" is smaller than the initial population.
Deviations from HWE
I. Mutation
II. Migration
III. Non-Random Mating
IV. Genetic Drift
V. The Neutral Theory
A. Variation
B. Genetic Load
1. "HARD" Selection can 'cost' a population individuals:
- those that die as a consequence of differential fitness values.
- the "breeding population" is smaller than the initial population.
- Reproductive output must compensate for this loss of individuals
Deviations from HWE
I. Mutation
II. Migration
III. Non-Random Mating
IV. Genetic Drift
V. The Neutral Theory
A. Variation
B. Genetic Load
1. "HARD" Selection can 'cost' a population individuals:
- those that die as a consequence of differential fitness values.
- the "breeding population" is smaller than the initial population.
- Reproductive output must compensate for this loss of individuals
- The stronger the "hard" selection, the more individuals are lost and
the higher the compensatory reproductive effort must be.
Deviations from HWE
I. Mutation
II. Migration
III. Non-Random Mating
IV. Genetic Drift
V. The Neutral Theory
A. Variation
B. Genetic Load
1. "HARD" Selection can 'cost' a population individuals:
- those that die as a consequence of differential fitness values.
- the "breeding population" is smaller than the initial population.
- Reproductive output must compensate for this loss of individuals
- The stronger the "hard" selection, the more individuals are lost and
the higher the compensatory reproductive effort must be.
- The 'cost' of replacing an allele with a new, adaptive allele =
"Genetic Load" (L) L = (optimal fitness - mean fitness)/optimal fitness.
Essentially, this is a measure of the proportion of individuals that will die as a
consequence of this "hard" selection. The lower the mean fitness, the further
the population is from the optimum, and the more deaths there will be.
B. Genetic Load
1. "HARD" Selection can 'cost' a population individuals:
2. Why is this a problem?
B. Genetic Load
1. "HARD" Selection can 'cost' a population individuals:
2. Why is this a problem?
- If variation is maintained by selection, we are probably talking
about "heterosis" - selection for the heterozygote where the heterozygote
has the highest fitness (and both alleles are maintained). (Selection against
the heterozygote can only maintain variation at equilibrium, and this is
unstable).
B. Genetic Load
1. "HARD" Selection can 'cost' a population individuals:
2. Why is this a problem?
- If variation is maintained by selection, we are probably talking
about "heterosis" - selection for the heterozygote where the heterozygote
has the highest fitness (and both alleles are maintained).
- The problem is that load can be high in this situation, because lots
of homozygotes are produced each generation, just to die by selection.
B. Genetic Load
1. "HARD" Selection can 'cost' a population individuals:
2. Why is this a problem?
- If variation is maintained by selection, we are probably talking
about "heterosis" - selection for the heterozygote where the heterozygote
has the highest fitness (and both alleles are maintained).
- The problem is that load can be high in this situation, because lots
of homozygotes are produced each generation, just to die by selection.
- Let's consider even a "best case" scenario:
B. Genetic Load
1. "HARD" Selection can 'cost' a population individuals:
2. Why is this a problem?
- If variation is maintained by selection, we are probably talking
about "heterosis" - selection for the heterozygote where the heterozygote
has the highest fitness (and both alleles are maintained).
- The problem is that load can be high in this situation, because lots
of homozygotes are produced each generation, just to die by selection.
- Let's consider even a "best case" scenario:
- mean fitness = 1 - H((s+t)/2)
B. Genetic Load
1. "HARD" Selection can 'cost' a population individuals:
2. Why is this a problem?
- If variation is maintained by selection, we are probably talking
about "heterosis" - selection for the heterozygote where the heterozygote
has the highest fitness (and both alleles are maintained).
- The problem is that load can be high in this situation, because lots
of homozygotes are produced each generation, just to die by selection.
- Let's consider even a "best case" scenario:
- mean fitness = 1 - H((s+t)/2)
- If s and t = .1 (very weak), and H = .33 (average for Drosophila,
above), then the mean fitness = 0.967.
B. Genetic Load
1. "HARD" Selection can 'cost' a population individuals:
2. Why is this a problem?
- If variation is maintained by selection, we are probably talking
about "heterosis" - selection for the heterozygote where the heterozygote
has the highest fitness (and both alleles are maintained).
- The problem is that load can be high in this situation, because lots
of homozygotes are produced each generation, just to die by selection.
- Let's consider even a "best case" scenario:
- mean fitness = 1 - H((s+t)/2)
- If s and t = .1 (very weak), and H = .33 (average for Drosophila,
above), then the mean fitness = 0.967.
- Not bad; not much death due to selection in this situation...
B. Genetic Load
1. "HARD" Selection can 'cost' a population individuals:
2. Why is this a problem?
- If variation is maintained by selection, we are probably talking
about "heterosis" - selection for the heterozygote where the heterozygote
has the highest fitness (and both alleles are maintained).
- The problem is that load can be high in this situation, because lots
of homozygotes are produced each generation, just to die by selection.
- Let's consider even a "best case" scenario:
- mean fitness = 1 - H((s+t)/2)
- If s and t = .1 (very weak), and H = .33 (average for Drosophila,
above), then the mean fitness = 0.967.
- Not bad; not much death due to selection in this situation...
- HOWEVER, there are 3000 polymorphic loci across the genome.
So, mean fitness across the genome = (0.967)^3000!
B. Genetic Load
1. "HARD" Selection can 'cost' a population individuals:
2. Why is this a problem?
- If variation is maintained by selection, we are probably talking
about "heterosis" - selection for the heterozygote where the heterozygote
has the highest fitness (and both alleles are maintained).
- The problem is that load can be high in this situation, because lots
of homozygotes are produced each generation, just to die by selection.
- Let's consider even a "best case" scenario:
- mean fitness = 1 - H((s+t)/2)
- If s and t = .1 (very weak), and H = .33 (average for Drosophila,
above), then the mean fitness = 0.967.
- Not bad; not much death due to selection in this situation...
- HOWEVER, there are 3000 polymorphic loci across the genome.
So, mean fitness across the genome = (0.967)^3000! This becomes
ridiculously LOW (0.19 x 10-44) relative to the best case genome that is
heterozygous at every one of the 3000 loci. - So, some individuals die
because they are homozygous (and less fit) at A, others die because they are
homozygous (and less fit) at B, other die because they are homozygous (and
less fit) at C, and so forth...
B. Genetic Load
1. "HARD" Selection can 'cost' a population individuals:
2. Why is this a problem?
- If variation is maintained by selection, we are probably talking
about "heterosis" - selection for the heterozygote where the heterozygote
has the highest fitness (and both alleles are maintained).
- The problem is that load can be high in this situation, because lots
of homozygotes are produced each generation, just to die by selection.
- Let's consider even a "best case" scenario:
- mean fitness = 1 - H((s+t)/2)
- If s and t = .1 (very weak), and H = .33 (average for Drosophila,
above), then the mean fitness = 0.967.
- Not bad; not much death due to selection in this situation...
In this case, the load is SO GREAT across the genome that almost NOBODY
lives to reproduce. And those that do can not possibly produce enough
offspring to compensate for this amount of death.
B. Genetic Load
1. "HARD" Selection can 'cost' a population individuals:
2. Why is this a problem?
So, hard selection can not be SOLELY responsible for the variation we
observe... a population could not sustain itself under this amount of genetic
load...
B. Genetic Load
1. "HARD" Selection can 'cost' a population individuals:
2. Why is this a problem?
3. Solutions
a. Selectionists
- Not all selection is "hard", imposing additional deaths above
background mortality.
B. Genetic Load
1. "HARD" Selection can 'cost' a population individuals:
2. Why is this a problem?
3. Solutions
a. Selectionists
- Not all selection is "hard", imposing additional deaths above
background mortality.
- There is also "soft" selection, in which the death due to selection
occurs as a component of background mortality, not in addition to it.
B. Genetic Load
1. "HARD" Selection can 'cost' a population individuals:
2. Why is this a problem?
3. Solutions
a. Selectionists
- Not all selection is "hard", imposing additional deaths above
background mortality.
- There is also "soft" selection, in which the death due to selection
occurs as a component of background mortality, not in addition to it.
- For instance, consider territoriality or competition for a resource.
Suppose there is only enough food or space to support 50 individuals, but 60
offspring are produced each generation. Well, each generation there are 10
deaths and there are 50 “survivors".
B. Genetic Load
1. "HARD" Selection can 'cost' a population individuals:
2. Why is this a problem?
3. Solutions
a. Selectionists
- Suppose we have a population of aa homozygotes initially. All the
territories are occupied by aa individuals and 10 individuals die.
B. Genetic Load
1. "HARD" Selection can 'cost' a population individuals:
2. Why is this a problem?
3. Solutions
a. Selectionists
- Suppose we have a population of aa homozygotes initially. All the
territories are occupied by aa individuals and 10 individuals die.
- Well, If an 'A' allele is produce by mutation and heterozygotes have
the highest relative fitness (probability of acquiring a territory), then the allele
"A" increase in frequency to equilibrium....
B. Genetic Load
1. "HARD" Selection can 'cost' a population individuals:
2. Why is this a problem?
3. Solutions
a. Selectionists
- Suppose we have a population of aa homozygotes initially. All the
territories are occupied by aa individuals and 10 individuals die.
- Well, If an 'A' allele is produce by mutation and heterozygotes have
the highest relative fitness (probability of acquiring a territory), then the allele
"A" increase in frequency to equilibrium....
- Selection occurs, BUT THERE ARE STILL ONLY 10 DEATHS PER
GENERATION.
B. Genetic Load
1. "HARD" Selection can 'cost' a population individuals:
2. Why is this a problem?
3. Solutions
a. Selectionists
- Suppose we have a population of aa homozygotes initially. All the
territories are occupied by aa individuals and 10 individuals die.
- Well, If an 'A' allele is produce by mutation and heterozygotes have
the highest relative fitness (probability of acquiring a territory), then the allele
"A" increase in frequency to equilibrium....
- Selection occurs, BUT THERE ARE STILL ONLY 10 DEATHS PER
GENERATION.
- In this case there is NO genetic load, as selection is NOT causing
ADDITIONAL mortality. It is just changing the probability of who dies.
B. Genetic Load
1. "HARD" Selection can 'cost' a population individuals:
2. Why is this a problem?
3. Solutions
a. Selectionists
- Suppose we have a population of aa homozygotes initially. All the
territories are occupied by aa individuals and 10 individuals die.
- Well, If an 'A' allele is produce by mutation and heterozygotes have
the highest relative fitness (probability of acquiring a territory), then the allele
"A" increase in frequency to equilibrium....
- Selection occurs, BUT THERE ARE STILL ONLY 10 DEATHS PER
GENERATION.
- In this case there is NO genetic load, as selection is NOT causing
ADDITIONAL mortality. It is just changing the probability of who dies.
- So, selection across lots of loci does not NECCESSARILY lead to
impossible loads.... as long as it is SOFT SELECTION
B. Genetic Load
1. "HARD" Selection can 'cost' a population individuals:
2. Why is this a problem?
3. Solutions
a. Selectionists
b. Neutralists
B. Genetic Load
1. "HARD" Selection can 'cost' a population individuals:
2. Why is this a problem?
3. Solutions
a. Selectionists
b. Neutralists
- Maybe MOST of this variation is NEUTRAL, and is simply
maintained by drift as new mutant alleles sequentially replace one another.
B. Genetic Load
1. "HARD" Selection can 'cost' a population individuals:
2. Why is this a problem?
3. Solutions
a. Selectionists
b. Neutralists
- Maybe MOST of this variation is NEUTRAL, and is simply
maintained by drift as new mutant alleles sequentially replace one another.
c. In a sense, the argument is really about selection.
B. Genetic Load
1. "HARD" Selection can 'cost' a population individuals:
2. Why is this a problem?
3. Solutions
a. Selectionists
b. Neutralists
- Maybe MOST of this variation is NEUTRAL, as is simply maintained
by drift as new mutant alleles sequentially replace one another.
c. In a sense, the argument is really about selection.
Selectionists state that selection is important for 2 reasons - it eliminates bad
alleles and FAVORS advantageous alleles.
B. Genetic Load
1. "HARD" Selection can 'cost' a population individuals:
2. Why is this a problem?
3. Solutions
a. Selectionists
b. Neutralists
- Maybe MOST of this variation is NEUTRAL, as is simply maintained
by drift as new mutant alleles sequentially replace one another.
c. In a sense, the argument is really about selection.
Selectionists state that selection is important for 2 reasons - it eliminates bad
alleles and FAVORS advantageous alleles.
Neutralists agree that selection weeds out deleterious alleles, but they claim
that this leaves a set of alleles that are functionally equivalent - neutral - in
relative value.
And changes in these equivalent alleles occur as a consequence of drift.
Deviations from HWE
I. Mutation
II. Migration
III. Non-Random Mating
IV. Genetic Drift
V. The Neutral Theory
C. Neutral Variation
Motoo Kimura
1924-1994
V. The Neutral Theory
C. Neutral Variation
- Variation occurs at many levels, from genes to proteins to physical
and behavioral characteristics of organisms.
V. The Neutral Theory
C. Neutral Variation
- Variation occurs at many levels, from genes to proteins to physical
and behavioral characteristics of organisms.
- adaptive phenotypic variation is due to selection.
V. The Neutral Theory
C. Neutral Variation
- Variation occurs at many levels, from genes to proteins to physical
and behavioral characteristics of organisms.
- adaptive phenotypic variation is due to selection.
- But is ALL genetic variation of selective value?
V. The Neutral Theory
C. Neutral Variation
- Variation occurs at many levels, from genes to proteins to physical
and behavioral characteristics of organisms.
- adaptive phenotypic variation is due to selection.
- But is ALL genetic variation of selective value?
- "no"; obviously, silent mutations are not maintained by selection
V. The Neutral Theory
C. Neutral Variation
- Variation occurs at many levels, from genes to proteins to physical
and behavioral characteristics of organisms.
- adaptive phenotypic variation is due to selection.
- But is ALL genetic variation of selective value?
- "no"; obviously, silent mutations are not maintained by selection So, Kimura suggested that there is too much variation at the DNA level to be
explained by selection... he suggested that MOST of the variation in DNA is of
NO selective value - it is NEUTRAL VARIATION.
V. The Neutral Theory
C. Neutral Variation
- Variation occurs at many levels, from genes to proteins to physical
and behavioral characteristics of organisms.
- adaptive phenotypic variation is due to selection.
- But is ALL genetic variation of selective value?
- "no"; obviously, silent mutations are not maintained by selection So, Kimura suggested that there is too much variation at the DNA level to be
explained by selection... he suggested that MOST of the variation in DNA is of
NO selective value - it is NEUTRAL VARIATION.
- Curiously, the rate of replacement by drift, alone = the rate of
mutation:
V. The Neutral Theory
C. Neutral Variation
- Variation occurs at many levels, from genes to proteins to physical
and behavioral characteristics of organisms.
- adaptive phenotypic variation is due to selection.
- But is ALL genetic variation of selective value?
- "no"; obviously, silent mutations are not maintained by selection So, Kimura suggested that there is too much variation at the DNA level to be
explained by selection... he suggested that MOST of the variation in DNA is of
NO selective value - it is NEUTRAL VARIATION.
- Curiously, the rate of replacement by drift, alone = the rate of
mutation:
1) The number of new alleles produced at a locus = 2N(m), where m
is the mutation rate.
V. The Neutral Theory
C. Neutral Variation
- Variation occurs at many levels, from genes to proteins to physical
and behavioral characteristics of organisms.
- adaptive phenotypic variation is due to selection.
- But is ALL genetic variation of selective value?
- "no"; obviously, silent mutations are not maintained by selection So, Kimura suggested that there is too much variation at the DNA level to be
explained by selection... he suggested that MOST of the variation in DNA is of
NO selective value - it is NEUTRAL VARIATION.
- Curiously, the rate of replacement by drift, alone = the rate of
mutation:
1) The number of new alleles produced at a locus = 2N(m), where m
is the mutation rate.
- So, if the average mutation rate is 1 in 10,000, but there are 20,000
individuals (2N = 40,000 alleles), then on average 4 new alleles will be
produced by mutation every generation.
V. The Neutral Theory
C. Neutral Variation
- Variation occurs at many levels, from genes to proteins to physical
and behavioral characteristics of organisms.
- adaptive phenotypic variation is due to selection.
- But is ALL genetic variation of selective value?
- "no"; obviously, silent mutations are not maintained by selection So, Kimura suggested that there is too much variation at the DNA level to be
explained by selection... he suggested that MOST of the variation in DNA is of
NO selective value - it is NEUTRAL VARIATION.
- Curiously, the rate of replacement by drift, alone = the rate of
mutation:
1) The number of new alleles produced at a locus = 2N(m), where m
is the mutation rate.
- So, if the average mutation rate is 1 in 10,000, but there are 20,000
individuals (2N = 40,000 alleles), then on average 4 new alleles will be
produced by mutation every generation.
2) Each allele has a probability of fixation = 1/2N.
V. The Neutral Theory
C. Neutral Variation
- Variation occurs at many levels, from genes to proteins to physical
and behavioral characteristics of organisms.
- adaptive phenotypic variation is due to selection.
- But is ALL genetic variation of selective value?
- "no"; obviously, silent mutations are not maintained by selection So, Kimura suggested that there is too much variation at the DNA level to be
explained by selection... he suggested that MOST of the variation in DNA is of
NO selective value - it is NEUTRAL VARIATION.
- Curiously, the rate of replacement by drift, alone = the rate of
mutation:
1) The number of new alleles produced at a locus = 2N(m), where m
is the mutation rate.
- So, if the average mutation rate is 1 in 10,000, but there are 20,000
individuals (2N = 40,000 alleles), then on average 4 new alleles will be
produced by mutation every generation.
2) Each allele has a probability of fixation = 1/2N.
3) So, the rate of replacement = (number of new alleles formed) x
(probability one become fixed) = 2N(m) x 1/2N = m per generation.
V. The Neutral Theory
C. Neutral Variation
D. Predictions and Results
V. The Neutral Theory
C. Neutral Variation
D. Predictions and Results
1. Rates of molecular evolution should vary in functional and nonfunctional regions
V. The Neutral Theory
C. Neutral Variation
D. Predictions and Results
1. Rates of molecular evolution should vary in functional and nonfunctional regions
- Rates should vary in different codon positions. Variation at the
third position should be higher, because these are usually silent mutations.
Mutations at the first two position change amino acids, and these changes
are deleterious.
V. The Neutral Theory
C. Neutral Variation
D. Predictions and Results
1. Rates of molecular evolution should vary in functional and nonfunctional regions
- Rates should vary in different codon positions. Variation at the
third position should be higher, because these are usually silent mutations.
Mutations at the second position change amino acids, and these changes are
deleterious. PATTERN CONFIRMED.
V. The Neutral Theory
C. Neutral Variation
D. Predictions and Results
1. Rates of molecular evolution should vary in functional and nonfunctional regions
- Rates should vary in different codon positions. Variation at the
third position should be higher, because these are usually silent mutations.
Mutations at the second position change amino acids, and these changes are
deleterious. PATTERN CONFIRMED.
- Rates should vary in coding and non-coding regions. Variation in
Introns should occur more rapidly than variation in exons, since introns are
not transcribed and are also invisible to selection.
V. The Neutral Theory
C. Neutral Variation
D. Predictions and Results
1. Rates of molecular evolution should vary in functional and nonfunctional regions
- Rates should vary in different codon positions. Variation at the
third position should be higher, because these are usually silent mutations.
Mutations at the second position change amino acids, and these changes are
deleterious. PATTERN CONFIRMED.
- Rates should vary in coding and non-coding regions. Variation in
Introns should occur more rapidly than variation in exons, since introns are
not transcribed and are also invisible to selection. PATTERN CONFIRMED
V. The Neutral Theory
C. Neutral Variation
D. Predictions and Results
1. Rates of molecular evolution should vary in functional and nonfunctional regions
- Rates should vary in different codon positions. Variation at the
third position should be higher, because these are usually silent mutations.
Mutations at the second position change amino acids, and these changes are
deleterious. PATTERN CONFIRMED.
- Rates should vary in coding and non-coding regions. Variation in
Introns should occur more rapidly than variation in exons, since introns are
not transcribed and are also invisible to selection. PATTERN CONFIRMED
- Rates should vary in functional and non-functional regions of
proteins.
V. The Neutral Theory
C. Neutral Variation
D. Predictions and Results
1. Rates of molecular evolution should vary in functional and nonfunctional regions
- Rates should vary in different codon positions. Variation at the
third position should be higher, because these are usually silent mutations.
Mutations at the second position change amino acids, and these changes are
deleterious. PATTERN CONFIRMED.
- Rates should vary in coding and non-coding regions. Variation in
Introns should occur more rapidly than variation in exons, since introns are
not transcribed and are also invisible to selection. PATTERN CONFIRMED
- Rates should vary in functional and non-functional regions of
proteins. PATTERN CONFIRMED
V. The Neutral Theory
C. Neutral Variation
D. Predictions and Results
1. Rates of molecular evolution should vary in functional and nonfunctional regions
- Rates should vary in different codon positions. Variation at the
third position should be higher, because these are usually silent mutations.
Mutations at the second position change amino acids, and these changes are
deleterious. PATTERN CONFIRMED.
- Rates should vary in coding and non-coding regions. Variation in
Introns should occur more rapidly than variation in exons, since introns are
not transcribed and are also invisible to selection. PATTERN CONFIRMED
- Rates should vary in functional and non-functional regions of
proteins. PATTERN CONFIRMED
- Rates should vary between vital proteins and less vital proteins.
V. The Neutral Theory
C. Neutral Variation
D. Predictions and Results
1. Rates of molecular evolution should vary in functional and nonfunctional regions
- Rates should vary in different codon positions. Variation at the
third position should be higher, because these are usually silent mutations.
Mutations at the second position change amino acids, and these changes are
deleterious. PATTERN CONFIRMED.
- Rates should vary in coding and non-coding regions. Variation in
Introns should occur more rapidly than variation in exons, since introns are
not transcribed and are also invisible to selection. PATTERN CONFIRMED
- Rates should vary in functional and non-functional regions of
proteins. PATTERN CONFIRMED
- Rates should vary between vital proteins and less vital proteins.
PATTERN CONFIRMED
V. The Neutral Theory
C. Neutral Variation
D. Predictions and Results
1. Rates of molecular evolution should vary in functional and nonfunctional regions
2. Rates of replacement (substitution of one fixed allele by another
that reaches fixation) should be constant over geologic time.
V. The Neutral Theory
C. Neutral Variation
D. Predictions and Results
1. Rates of molecular evolution should vary in functional and nonfunctional regions
2. Rates of replacement (substitution of one fixed allele by another
that reaches fixation) should be constant over geologic time.
- If changes are random and occur at a given rate, then they should
"tick" along like a clock.
V. The Neutral Theory
C. Neutral Variation
D. Predictions and Results
1. Rates of molecular evolution should vary in functional and nonfunctional regions
2. Rates of replacement (substitution of one fixed allele by another
that reaches fixation) should be constant over geologic time.
- If changes are random and occur at a given rate, then they should
"tick" along like a clock.
- Selection should slow change when an adapted complex occurs,
and speed rates when a new adaptive combination occurs, like in obviously
adaptive morphological traits. - PATTERNS CONFIRMED (usually).
V. The Neutral Theory
C. Neutral Variation
D. Predictions and Results
1. Rates of molecular evolution should vary in functional and nonfunctional regions
2. Rates of replacement (substitution of one fixed allele by another
that reaches fixation) should be constant over geologic time.
- If changes are random and occur at a given rate, then they should
"tick" along like a clock.
- Selection should slow change when an adapted complex occurs,
and speed rates when a new adaptive combination occurs, like in obviously
adaptive morphological traits. - PATTERNS CONFIRMED (usually).
V. The Neutral Theory
C. Neutral Variation
D. Predictions and Results
1. Rates of molecular evolution should vary in functional and nonfunctional regions
2. Rates of replacement (substitution of one fixed allele by another
that reaches fixation) should be constant over geologic time.
3. Rates of morphological change should be independent of the rate
of molecular change.
V. The Neutral Theory
C. Neutral Variation
D. Predictions and Results
1. Rates of molecular evolution should vary in functional and nonfunctional regions
2. Rates of replacement (substitution of one fixed allele by another
that reaches fixation) should be constant over geologic time.
3. Rates of morphological change should be independent of the rate
of molecular change.
- "Living Fossils" show extreme genetic change and variation, yet
have remained morphologically unchanged for millenia. And, the rate of
genetic change in this morphologically constant species is the same as in
hominids, which have changed dramatically in morphology over a short
period.
V. The Neutral Theory
C. Neutral Variation
D. Predictions and Results
1. Rates of molecular evolution should vary in functional and nonfunctional regions
2. Rates of replacement (substitution of one fixed allele by another
that reaches fixation) should be constant over geologic time.
3. Rates of morphological change should be independent of the rate
of molecular change.
- "Living Fossils" show extreme genetic change and variation, yet
have remained morphologically unchanged for millenia. And, the rate of
genetic change in this morphologically constant species is the same as in
hominids, which have changed dramatically in morphology over a short
period. PATTERN CONFIRMED
V. The Neutral Theory
C. Neutral Variation
D. Predictions and Results
E. Problems and Resolutions
V. The Neutral Theory
C. Neutral Variation
D. Predictions and Results
E. Problems and Resolutions
1. Selection also explains different mutation rates in functional and
non-functional regions
V. The Neutral Theory
C. Neutral Variation
D. Predictions and Results
E. Problems and Resolutions
1. Selection also explains different mutation rates in functional and
non-functional regions
Essentially, since most adaptive changes should be slight, fewer mutations
in functional regions are likely to improve function. So, the rate of change is
"constrained" to only those changes that are neutral or ADAPTIVE. Also, a
change of one AA is likely to cause a smaller change if it is in a less
functional region. "Tweeking" less functional regions might be adaptive,
whereas "tweeking" functional regions are more likely to be deleterious.
V. The Neutral Theory
C. Neutral Variation
D. Predictions and Results
E. Problems and Resolutions
1. Selection also explains different mutation rates in functional and
non-functional regions
2. A truly neutral clock should tick off mutations at a constant rate.
But should this ticking occur per unit time, or per generation?
V. The Neutral Theory
C. Neutral Variation
D. Predictions and Results
E. Problems and Resolutions
1. Selection also explains different mutation rates in functional and
non-functional regions
2. A truly neutral clock should tick off mutations at a constant rate.
But should this ticking occur per unit time, or per generation?
- Since mutations produce new alleles (a new "tick"), and mutations
only occur during replication of the DNA, it would seem that a truly neutral
clock should tick at a rate dependent on the generation time of the organism.
V. The Neutral Theory
C. Neutral Variation
D. Predictions and Results
E. Problems and Resolutions
1. Selection also explains different mutation rates in functional and
non-functional regions
2. A truly neutral clock should tick off mutations at a constant rate.
But should this ticking occur per unit time, or per generation?
- Since mutations produce new alleles (a new "tick"), and mutations
only occur during replication of the DNA, it would seem that a truly neutral
clock should tick at a rate dependent on the generation time of the organism.
- Species with rapid generation times should accumulate mutations
at a faster rate than long-lived species with slower generation times.
V. The Neutral Theory
C. Neutral Variation
D. Predictions and Results
E. Problems and Resolutions
1. Selection also explains different mutation rates in functional and
non-functional regions
2. A truly neutral clock should tick off mutations at a constant rate.
But should this ticking occur per unit time, or per generation?
- Since mutations produce new alleles (a new "tick"), and mutations
only occur during replication of the DNA, it would seem that a truly neutral
clock should tick at a rate dependent on the generation time of the organism.
- Species with rapid generation times should accumulate mutations
at a faster rate than long-lived species with slower generation times.
- This is true of non-coding DNA... but not true for proteins, as we
have seen. Proteins accumulate mutations in absolute time, not generational
time.
V. The Neutral Theory
C. Neutral Variation
D. Predictions and Results
E. Problems and Resolutions
1. Selection also explains different mutation rates in functional and
non-functional regions
2. A truly neutral clock should tick off mutations at a constant rate.
But should this ticking occur per unit time, or per generation?
- Since mutations produce new alleles (a new "tick"), and mutations
only occur during replication of the DNA, it would seem that a truly neutral
clock should tick at a rate dependent on the generation time of the organism.
- Species with rapid generation times should accumulate mutations
at a faster rate than long-lived species with slower generation times.
- This is true of non-coding DNA... but not true for proteins, as we
have seen. Proteins accumulate mutations in absolute time, not generational
time. THIS IS INCONSISTENT WITH THE NEUTRAL MODEL
V. The Neutral Theory
C. Neutral Variation
D. Predictions and Results
E. Problems and Resolutions
F. The Nearly Neutral Model (Ohta)
V. The Neutral Theory
C. Neutral Variation
D. Predictions and Results
E. Problems and Resolutions
F. The Nearly Neutral Model (Ohta)
- Ohta included the very weak effect against slightly deleterious
mutations. He found that, if s < 1/2Ne, then alleles are essentially neutral and
become fixed as drift would predict.
V. The Neutral Theory
C. Neutral Variation
D. Predictions and Results
E. Problems and Resolutions
F. The Nearly Neutral Model (Ohta)
- Ohta included the very weak effect against slightly deleterious
mutations. He found that, if s < 1/2Ne, then alleles are essentially neutral and
become fixed as drift would predict.
- In other words, in small populations, drift predominates unless
selection is fairly strong (in a population of Ne = 5, drift will predominante
unless s > 0.1).
V. The Neutral Theory
C. Neutral Variation
D. Predictions and Results
E. Problems and Resolutions
F. The Nearly Neutral Model (Ohta)
- Ohta included the very weak effect against slightly deleterious
mutations. He found that, if s < 1/2Ne, then alleles are essentially neutral and
become fixed as drift would predict.
- In other words, in small populations, drift predominates unless
selection is fairly strong (in a population of Ne = 5, drift will predominante
unless s > 0.1).
- In large populations, selection predominates, even if it is fairly
weak (if Ne = 10,000, then selection will predominate if s > 0.00005).
V. The Neutral Theory
C. Neutral Variation
D. Predictions and Results
E. Problems and Resolutions
F. The Nearly Neutral Model (Ohta)
SO..... (GET READY FOR THIS!!!!)
F. The Nearly Neutral Model (Ohta)
Sub. Rate
SO.
- We observe a constant AA substitution rate across species, even
though we would expect that species with shorter generation times should
have FASTER rates of substitution.
OBS.
EXP.
Short
GEN TIME
Long
F. The Nearly Neutral Model (Ohta)
SO.
- We observe a constant AA substitution rate across species, even
though we would expect that species with shorter generation times should
have FASTER rates of substitution.
- So, something must be 'slowing down' this rate of substitution in
species with short gen. times. What's slowing it down is their large
populations size, such that the effects of drift, alone, are reduced.
Sub. Rate
LARGE
POP. SIZE
OBS.
EXP.
Short
GEN TIME
Long
F. The Nearly Neutral Model (Ohta)
SO.
- We observe a constant AA substitution rate across species, even
though we would expect that species with shorter generation times should
have FASTER rates of substitution.
- So, something must be 'slowing down' this rate of substitution in
species with short gen. times. What's slowing it down is their large
populations size, such that the effects of drift, alone, are reduced.
- Likewise, species with long generation times have small
populations, and substitution by drift and fixation is more rapid than
expected based on generation time, alone.
Sub. Rate
SMALL POP.
SIZE
OBS.
EXP.
Short
GEN TIME
Long
F. The Nearly Neutral Model (Ohta)
SO.
- We observe a constant AA substitution rate across species, even
though we would expect that species with shorter generation times should
have FASTER rates of substitution.
- So, something must be 'slowing down' this rate of substitution in
species with short gen. times. What's slowing it down is their large
populations size, such that the effects of drift, alone, are reduced.
- Likewise, species with long generation times have small
populations, and substitution by drift and fixation is more rapid than
expected based on generation time, alone.
SMALL POP.
SIZE
Sub. Rate
SO.
- The constant
rate of AA
substitution
across species
is due to the
balance between
generation time
and population
size.
OBS.
EXP.
Short
GEN TIME
Long
V. The Neutral Theory
C. Neutral Variation
D. Predictions and Results
E. Problems and Resolutions
F. The Nearly Neutral Model (Ohta)
SO.
- The constant rate of AA substitution across species with different
generation times is due to the counter-balancing effect of population size,
which is inversely correlated with generation time.
V. The Neutral Theory
C. Neutral Variation
D. Predictions and Results
E. Problems and Resolutions
F. The Nearly Neutral Model (Ohta)
G. Conclusions
V. The Neutral Theory
C. Neutral Variation
D. Predictions and Results
E. Problems and Resolutions
F. The Nearly Neutral Model (Ohta)
G. Conclusions
- Neutral variability certainly exists; in non-coding DNA, especially.
V. The Neutral Theory
C. Neutral Variation
D. Predictions and Results
E. Problems and Resolutions
F. The Nearly Neutral Model (Ohta)
G. Conclusions
- Neutral variability certainly exists; in non-coding DNA, especially.
- However, it is possible that selection maintains molecular variation
as well, particularly in coding regions.
V. The Neutral Theory
C. Neutral Variation
D. Predictions and Results
E. Problems and Resolutions
F. The Nearly Neutral Model (Ohta)
G. Conclusions
- Neutral variability certainly exists; in non-coding DNA, especially.
- However, it is possible that selection maintains molecular variation
as well, particularly in coding regions.
It is also possible that selection maintains variability in non-coding
regions, as well, if these are "functional" in a structural or regulatory manner.
IV. Selection and Other Factors
A. Mutation
IV. Selection and Other Factors
A. Mutation
- Mutation can maintain a deleterious allele in the
population against the effects of selection, such that:
IV. Selection and Other Factors
A. Mutation
- Mutation can maintain a deleterious allele in the
population against the effects of selection, such that:
q(eq) = √(m/s)
IV. Selection and Other Factors
A. Mutation
- Mutation can maintain a deleterious allele in the
population against the effects of selection, such that:
q(eq) = √(m/s)
- more deleterious alleles are maintained if m
increases, or if selection differential declines... (if it is
not that bad to have it)…
IV. Selection and Other Factors
A. Mutation
B. Drift and "Adaptive Landscapes"
1. Single Locus
- consider a locus with selection against the heterozygote
p = 0.4, q = 0.6
AA
Aa
aa
Parental "zygotes"
0.16
0.48
0.36
prob. of survival (fitness)
0.8
0.4
0.6
Relative Fitness
1
0.5
0.75
Corrected Fitness
1 + 0.5
1.0
1 + 0.25
formulae
1+s
peq = t/(s + t) = .25/.75 = 0.33
1+t
= 1.00
IV. Selection and Other Factors
A. Mutation
B. Drift and "Adaptive Landscapes"
1. Single Locus
- consider a locus with selection against the heterozygote
mean fitness
1.0
0.75
0
0.33
1.0
IV. Selection and Other Factors
A. Mutation
B. Drift and "Adaptive Landscapes"
1. Single Locus
- suppose there is random movement up the 'wrong' slope?
mean fitness
1.0
0.75
0
0.33
1.0
IV. Selection and Other Factors
A. Mutation
B. Drift and "Adaptive Landscapes"
1. Single Locus
- if this is a large pop
with no drift, the
population will
become fixed on the
'suboptimal' peak, (p
= 0, q = 1.0, w = 0.75).
mean fitness
1.0
0.75
0
0.33
1.0
IV. Selection and Other Factors
A. Mutation
B. Drift and "Adaptive Landscapes"
1. Single Locus
- BUT if it is small,
then drift may be
important... because
only DRIFT can
randomly BOUNCE
the gene freq's to the
other slope!
mean fitness
1.0
0.75
0
0.33
1.0
IV. Selection and Other Factors
A. Mutation
B. Drift and "Adaptive Landscapes"
1. Single Locus
- And then selection
can push the pop up
the most adaptive
slope!
mean fitness
1.0
0.75
0
0.33
1.0
IV. Selection and Other Factors
A. Mutation
B. Drift and "Adaptive Landscapes"
1. Single Locus
- The more shallow
the 'maladaptive
valley', (representing
weaker selection
differentials) the
easier it is for drift to
cross it...
mean fitness
1.0
0.75
0
0.33
1.0
IV. Selection and Other Factors
A. Mutation
B. Drift and "Adaptive Landscapes"
2. Two Loci - create a 3-D landscape, with "mean
fitness" as the 'topographic relief"
Suppose AAbb and
aaBB work well, but
combinations of the
two do not (epistatic,
like butterfly mimicry).
1.0
f(A)
f(B)
1.0
IV. Selection and Other Factors
A. Mutation
B. Drift and "Adaptive Landscapes"
2. Two Loci - create a 3-D landscape, with "mean
fitness" as the 'topographic relief"
Again, strong
selection or weak drift
will cause mean
fitness to move up
nearest slopes.
1.0
f(A)
f(B)
1.0
IV. Selection and Other Factors
A. Mutation
B. Drift and "Adaptive Landscapes"
2. Two Loci - create a 3-D landscape, with "mean
fitness" as the 'topographic relief"
Only strong drift or
weak selection and
some drift (shallow
valley) can cause the
population to cross
the maladaptive
valley.
1.0
f(A)
f(B)
1.0
IV. Selection and Other Factors
A. Mutation
B. Drift and "Adaptive Landscapes"
- so, the interactions between drift and selection
are necessary for a population to find the optimal
adaptive peak... think about this in the context of
peripatric speciation.... THINK HARD about this...