Medical Genetics
08基因变异的群体行为
Population Genetics
Medical Genetics
Medical Genetics
Medical Genetics
What is a population from a
genetic perspective?
A population in the genetic
sense,is not just a group of
individuals,but a breeding group
Medical Genetics
The genetics of a population
is concerned not only with the
genetic constitution of the
individuals but also with the
transmission of the genes from
one generation to the next,
Medical Genetics
In the transmission the genotypes of the
parents are broken down and a new set of
genotypes is constituted in the progeny,
from the genes transmitted in the gametes,
The genes carried by the population thus
have continuity from generation to
generation,but the genotypes in which they
appear do not,The genetic constitution of a
population,referring to the genes it carries,
is described by the array of gene
frequencies,that is by specification of the
alleles present at every locus and the
numbers or proportions of the different
alleles at each locus."
Medical Genetics
Goals of Population Genetics
1,To describe how the frequency of an
allele which controls a trait changes over
time；
2,To analyze the factors that lead to
changes in gene (allele) frequencies；
3,To determine how changes in gene (allele)
frequencies affect evolution and
speciation,
Medical Genetics
Why Study Populations and Gene
Frequencies
1,Genetic variability necessary for
evolutionary success;
2,Measuring genetic variability at many
loci can characterize a population;
3,Variability of phenotypic and molecular
traits are analyzed,
Medical Genetics
1,Variability and Gene (or Allelic) Frequencies
1,Genetic data for a population can be expressed
as gene or allelic frequencies;
2,All genes have at least two alleles;
3,Summation of all the allelic frequencies for a
population can be considered a description of
the population;
4,Frequencies can vary widely among the alleles
in a population;
5,Two populations of the same species do not
have to have the same allelic frequencies,
Medical Genetics
Genotypic frequencies
It describes the distribution of
genotypes in a population,
Medical Genetics
Example
Blood type locus; two alleles,M
or N,and three MM,MN,NN
genotypes are possible (the following
data was collected from a single
human population),
Medical Genetics
Genotye # of Individuals Genotypic Frequencies
MM 1787 MM=1787/6129=0.289
MN 3039 MN=3039/6129=0.50
NN 1303 NN=1303/6129=0.21
Total 6129
Medical Genetics
Deriving Gene (or Allelic) Frequencies
To determine the allelic frequencies we simply count
the number of M or N alleles and divide by the total
number of alleles,
f(M) = [(2 x 1787) + 3039]/12,258 = 0.5395
f(N) = [(2 x 1303) + 3039]/12,258 = 0.4605
By convention one of the alleles is given the
designation p and the other q,Also p + q = 1,
p=0.5395 and q=0.4605
Furthermore,a population is considered by
population geneticists to be polymorphic if two
alleles are segregating and the frequency of the
most frequent allele is less than 0.99,
Medical Genetics
Deriving allelic frequencies from
genotypic frequencies
The following example will illustrate how
to calculate allelic frequencies from
genotypic frequencies,It will also
demonstrate that two different populations
from the same species do not have to have
the same allelic frequencies,
Medical Genetics
Let,p=f(M) and q=f(N)
Thus,p=f(MM) + ? f(MN)
and q=f(NN) + ? f(MN),
,
Percent Allelic Frequencies
Location MM MN NN p q
Greenland 83.5 15.6 0.90 0.913 0.087
Iceland 31.2 51.5 17.30 0.569 0.431
Medical Genetics
So the results of the above data are,
Greenland,p=0.835 + ? (0.156)=0.913
and q=0.009 + ? (0.156)=0.087
Iceland,p=0.312 + ? (0.515)=0.569
and q=0.173 + ? (0.515)=0.431
Clearly the allelic frequencies vary
between these populations,
Medical Genetics
2,The Hardy-Weinberg Law
The Hardy-Weinberg Law
? The unifying concept of population
genetics
? Named after the two scientists who
simultaneously discovered the law
? The law predicts how gene frequencies will
be transmitted from generation to
generation given a specific set of
assumptions,
Medical Genetics
If an infinitely large,random mating population is
free from outside evolutionary forces (i.e,
mutation,migration and natural selection),
then the gene frequencies will not change over
time,and the frequencies in the next generation
will be,
p2 for the AA genotype
2pq for the Aa genotype,and
q2 for the aa genotype,
Medical Genetics
Let's examine the assumptions
and conclusions in more detail
starting first with the assumptions,
Medical Genetics
A.Infinitely large population
1,No such population actually exists,
2,The effect that is of concern is
genetic drift (a change in gene
frequency that is the result of
chance deviation from expected
genotypic frequencies) a problem in
small populations,
Medical Genetics
B,Random mating
Random mating - matings in a
population that occur in proportion to
their allelic frequencies,
Medical Genetics
For example,if the allelic frequencies in a
population are,
f(M) = 0.91
f(N) = 0.09
then the probability of MM individuals
occurring is 0.91 x 0.91 =0.828,
If a significant deviation occurred,
then random mating did not happen in
this population,
Medical Genetics
Within a population,random
mating can be occurring at some loci
but not at others,
Examples of random mating loci -
blood type,RFLP patterns
Examples of non-random mating loci
- intelligence,physical stature
Medical Genetics
C,No evolutionary forces affecting the
population
The principal forces are,
1,Mutation
2,Migration
3,Selection
Some loci in a population may be affected by these
forces,and others may not; those loci not
affected by the forces can by analyzed as a
Hardy-Weinberg population
Medical Genetics
Mathematical Derivation of the
Hardy-Weinberg Law
If p equals the frequency of allele
A in a population and q is the
frequency of allele a in the same
population,union of gametes would
occur with the following genotypic
frequencies,
Medical Genetics
*The gamete and offspring genotypes are in parentheses,
From the table,it is clear that the prediction regarding
genotypic frequencies after one generation of random mating is
correct,That is,
AA = p2; Aa = 2pq; and aa = q2
Female Gametes*
p
(A)
q
(a)
Male
Gametes
p
(A)
p2
(AA)
pq
(Aa)
q
(a)
pq
(Aa)
q2
(aa)
Medical Genetics
Prediction regarding stability of gene
frequencies
The following is a mathematical proof of the
second prediction,To determine the allelic
frequency,they can be derived from the genotypic
frequencies as shown above,
p = f(AA) + ?f(Aa) (substitute from the table on previous page)
p = p2 + ?(2pq) (factor out p and divide)
p = p(p + q) (p + q =1; therefore q =1 - p; make this substitution)
p = p [p + (1 - p)] (subtract and multiply)
p = p
Medical Genetics
Evolutionary Genetics
? The Hardy-Weinberg Law described a population
that exists in genetic equilibrium where allelic
frequencies do not change from generation to
generation,
? For evolution of a population to occur,the gene
frequencies of that population must undergo
change,
? Several factors can act to change fitness or the
ability to maintain allelic frequencies,
– Viability - ability to survive
– Fertility - ability to reproduce
? By altering the fitness of an individual,the mating
distribution will change,and consequently the
allelic frequencies will change and the population
will evolve,
Medical Genetics
3,Factors that Affect Stability of Gene Frequencies
A,Mutation
1,Classified as beneficial,harmful or neutral;
2,Can occur by point mutations ; or small insertions
or deletions of the nucleotide sequence;
3,Harmful mutations are lost if they reduce fitness;
4,If fitness is improved by a mutation,then the
frequency of that allele will increase from
generation to generation;
5,The mutation could be a change in one allele to
resemble one currently in the population,for
example from a dominant to a recessive allele;
Medical Genetics
6 The mutation could generate an entirely new allele,
– Most of these mutations though will be detrimental and lost,
– If the environment changes,the new mutant allele may be
favored and eventually become the dominant alelle in that
population,
– If the mutation is beneficial to the species as a whole,
migration must occur for it to spread to other populations of
the species,
7 Gene duplication favor mutational events,
– The duplicated gene can undergo mutations to generate a
new gene that has a similar,but a slightly modified function
for the organism,
– This type of evolution generates multigene families,
(Examples,hemoglobin and muscle genes in humans,and
seed storage and photosynthetic genes in plants)
Medical Genetics
B.Migration
1.The Hardy-Weinberg Law assumes the population
is closed,But for many populations this is not the
case,
2,Migration will change gene frequencies by
bringing in more copies of an allele already in the
population or by bringing in a new allele that has
arisen by mutation,
3,Because mutations do not occur in every
population,migration will be required for that
allele to spread throughout that species,
Medical Genetics
4,In a genetic context,migration requires the
introduction of new alleles into the population,
This will only occur after the migrant has
successfully mated with an individual in the
population,The term that is used to described
this introduction of new alleles is gene flow,
5,The two effects of migration are to,
(1) increase variability within a population
(2) prevent a population of that species from diverging to
the extent that it becomes a new species,
Medical Genetics
C,Selection
1,Mutation causes new functions for the individual,
2,These new forms may or may not add to the fitness of the
individual,
3,If the fitness of the individual leads to a reproductive advantage,
then the alleles present in that individual will be more prevalent
in the next generation of the population,
4,A population undergoes selection when certain alleles are
preferentially found in a new generation because of the increased
fitness of the parent,
5,The alleles in the individual with increased fitness will increase in
frequency in the population,
6,In a Darwinian context,mutation,migration and selection lead to
changes in gene frequencies,and the population evolves by
natural selection,
08基因变异的群体行为
Population Genetics
Medical Genetics
Medical Genetics
Medical Genetics
What is a population from a
genetic perspective?
A population in the genetic
sense,is not just a group of
individuals,but a breeding group
Medical Genetics
The genetics of a population
is concerned not only with the
genetic constitution of the
individuals but also with the
transmission of the genes from
one generation to the next,
Medical Genetics
In the transmission the genotypes of the
parents are broken down and a new set of
genotypes is constituted in the progeny,
from the genes transmitted in the gametes,
The genes carried by the population thus
have continuity from generation to
generation,but the genotypes in which they
appear do not,The genetic constitution of a
population,referring to the genes it carries,
is described by the array of gene
frequencies,that is by specification of the
alleles present at every locus and the
numbers or proportions of the different
alleles at each locus."
Medical Genetics
Goals of Population Genetics
1,To describe how the frequency of an
allele which controls a trait changes over
time；
2,To analyze the factors that lead to
changes in gene (allele) frequencies；
3,To determine how changes in gene (allele)
frequencies affect evolution and
speciation,
Medical Genetics
Why Study Populations and Gene
Frequencies
1,Genetic variability necessary for
evolutionary success;
2,Measuring genetic variability at many
loci can characterize a population;
3,Variability of phenotypic and molecular
traits are analyzed,
Medical Genetics
1,Variability and Gene (or Allelic) Frequencies
1,Genetic data for a population can be expressed
as gene or allelic frequencies;
2,All genes have at least two alleles;
3,Summation of all the allelic frequencies for a
population can be considered a description of
the population;
4,Frequencies can vary widely among the alleles
in a population;
5,Two populations of the same species do not
have to have the same allelic frequencies,
Medical Genetics
Genotypic frequencies
It describes the distribution of
genotypes in a population,
Medical Genetics
Example
Blood type locus; two alleles,M
or N,and three MM,MN,NN
genotypes are possible (the following
data was collected from a single
human population),
Medical Genetics
Genotye # of Individuals Genotypic Frequencies
MM 1787 MM=1787/6129=0.289
MN 3039 MN=3039/6129=0.50
NN 1303 NN=1303/6129=0.21
Total 6129
Medical Genetics
Deriving Gene (or Allelic) Frequencies
To determine the allelic frequencies we simply count
the number of M or N alleles and divide by the total
number of alleles,
f(M) = [(2 x 1787) + 3039]/12,258 = 0.5395
f(N) = [(2 x 1303) + 3039]/12,258 = 0.4605
By convention one of the alleles is given the
designation p and the other q,Also p + q = 1,
p=0.5395 and q=0.4605
Furthermore,a population is considered by
population geneticists to be polymorphic if two
alleles are segregating and the frequency of the
most frequent allele is less than 0.99,
Medical Genetics
Deriving allelic frequencies from
genotypic frequencies
The following example will illustrate how
to calculate allelic frequencies from
genotypic frequencies,It will also
demonstrate that two different populations
from the same species do not have to have
the same allelic frequencies,
Medical Genetics
Let,p=f(M) and q=f(N)
Thus,p=f(MM) + ? f(MN)
and q=f(NN) + ? f(MN),
,
Percent Allelic Frequencies
Location MM MN NN p q
Greenland 83.5 15.6 0.90 0.913 0.087
Iceland 31.2 51.5 17.30 0.569 0.431
Medical Genetics
So the results of the above data are,
Greenland,p=0.835 + ? (0.156)=0.913
and q=0.009 + ? (0.156)=0.087
Iceland,p=0.312 + ? (0.515)=0.569
and q=0.173 + ? (0.515)=0.431
Clearly the allelic frequencies vary
between these populations,
Medical Genetics
2,The Hardy-Weinberg Law
The Hardy-Weinberg Law
? The unifying concept of population
genetics
? Named after the two scientists who
simultaneously discovered the law
? The law predicts how gene frequencies will
be transmitted from generation to
generation given a specific set of
assumptions,
Medical Genetics
If an infinitely large,random mating population is
free from outside evolutionary forces (i.e,
mutation,migration and natural selection),
then the gene frequencies will not change over
time,and the frequencies in the next generation
will be,
p2 for the AA genotype
2pq for the Aa genotype,and
q2 for the aa genotype,
Medical Genetics
Let's examine the assumptions
and conclusions in more detail
starting first with the assumptions,
Medical Genetics
A.Infinitely large population
1,No such population actually exists,
2,The effect that is of concern is
genetic drift (a change in gene
frequency that is the result of
chance deviation from expected
genotypic frequencies) a problem in
small populations,
Medical Genetics
B,Random mating
Random mating - matings in a
population that occur in proportion to
their allelic frequencies,
Medical Genetics
For example,if the allelic frequencies in a
population are,
f(M) = 0.91
f(N) = 0.09
then the probability of MM individuals
occurring is 0.91 x 0.91 =0.828,
If a significant deviation occurred,
then random mating did not happen in
this population,
Medical Genetics
Within a population,random
mating can be occurring at some loci
but not at others,
Examples of random mating loci -
blood type,RFLP patterns
Examples of non-random mating loci
- intelligence,physical stature
Medical Genetics
C,No evolutionary forces affecting the
population
The principal forces are,
1,Mutation
2,Migration
3,Selection
Some loci in a population may be affected by these
forces,and others may not; those loci not
affected by the forces can by analyzed as a
Hardy-Weinberg population
Medical Genetics
Mathematical Derivation of the
Hardy-Weinberg Law
If p equals the frequency of allele
A in a population and q is the
frequency of allele a in the same
population,union of gametes would
occur with the following genotypic
frequencies,
Medical Genetics
*The gamete and offspring genotypes are in parentheses,
From the table,it is clear that the prediction regarding
genotypic frequencies after one generation of random mating is
correct,That is,
AA = p2; Aa = 2pq; and aa = q2
Female Gametes*
p
(A)
q
(a)
Male
Gametes
p
(A)
p2
(AA)
pq
(Aa)
q
(a)
pq
(Aa)
q2
(aa)
Medical Genetics
Prediction regarding stability of gene
frequencies
The following is a mathematical proof of the
second prediction,To determine the allelic
frequency,they can be derived from the genotypic
frequencies as shown above,
p = f(AA) + ?f(Aa) (substitute from the table on previous page)
p = p2 + ?(2pq) (factor out p and divide)
p = p(p + q) (p + q =1; therefore q =1 - p; make this substitution)
p = p [p + (1 - p)] (subtract and multiply)
p = p
Medical Genetics
Evolutionary Genetics
? The Hardy-Weinberg Law described a population
that exists in genetic equilibrium where allelic
frequencies do not change from generation to
generation,
? For evolution of a population to occur,the gene
frequencies of that population must undergo
change,
? Several factors can act to change fitness or the
ability to maintain allelic frequencies,
– Viability - ability to survive
– Fertility - ability to reproduce
? By altering the fitness of an individual,the mating
distribution will change,and consequently the
allelic frequencies will change and the population
will evolve,
Medical Genetics
3,Factors that Affect Stability of Gene Frequencies
A,Mutation
1,Classified as beneficial,harmful or neutral;
2,Can occur by point mutations ; or small insertions
or deletions of the nucleotide sequence;
3,Harmful mutations are lost if they reduce fitness;
4,If fitness is improved by a mutation,then the
frequency of that allele will increase from
generation to generation;
5,The mutation could be a change in one allele to
resemble one currently in the population,for
example from a dominant to a recessive allele;
Medical Genetics
6 The mutation could generate an entirely new allele,
– Most of these mutations though will be detrimental and lost,
– If the environment changes,the new mutant allele may be
favored and eventually become the dominant alelle in that
population,
– If the mutation is beneficial to the species as a whole,
migration must occur for it to spread to other populations of
the species,
7 Gene duplication favor mutational events,
– The duplicated gene can undergo mutations to generate a
new gene that has a similar,but a slightly modified function
for the organism,
– This type of evolution generates multigene families,
(Examples,hemoglobin and muscle genes in humans,and
seed storage and photosynthetic genes in plants)
Medical Genetics
B.Migration
1.The Hardy-Weinberg Law assumes the population
is closed,But for many populations this is not the
case,
2,Migration will change gene frequencies by
bringing in more copies of an allele already in the
population or by bringing in a new allele that has
arisen by mutation,
3,Because mutations do not occur in every
population,migration will be required for that
allele to spread throughout that species,
Medical Genetics
4,In a genetic context,migration requires the
introduction of new alleles into the population,
This will only occur after the migrant has
successfully mated with an individual in the
population,The term that is used to described
this introduction of new alleles is gene flow,
5,The two effects of migration are to,
(1) increase variability within a population
(2) prevent a population of that species from diverging to
the extent that it becomes a new species,
Medical Genetics
C,Selection
1,Mutation causes new functions for the individual,
2,These new forms may or may not add to the fitness of the
individual,
3,If the fitness of the individual leads to a reproductive advantage,
then the alleles present in that individual will be more prevalent
in the next generation of the population,
4,A population undergoes selection when certain alleles are
preferentially found in a new generation because of the increased
fitness of the parent,
5,The alleles in the individual with increased fitness will increase in
frequency in the population,
6,In a Darwinian context,mutation,migration and selection lead to
changes in gene frequencies,and the population evolves by
natural selection,
