HARDY-WEINBERG

EQUILIBRIUM

By
Shahid Mahmood
University of Gujrat
Hafiz Hayat Campus, Gujrat
 INTRODUCTION

• In 1908, G. H. Hardy, a British mathematician,

and W. Weinberg, a German physician,
independently discovered a rule that relates
allelic and genotypic frequencies in a
population of diploid, sexually reproducing
individuals if that population has No random
mating, large size (no change in population
from large to small), no mutation or No
migration, and no selection
 Godfrey Hardy Wilhelm Weinberg

(1877-1947) (1862-1937)
 STATEMENT
“ the
allele and genotype frequencies in
a population remain constant from
generation to generation unless
specific disturbing influences are
introduced”
The rule has three aspects:
1. The allelic frequencies at an autosomal locus in a
population will not change from one generation to the next
(allelic-frequency equilibrium)
2. The genotypic frequencies of the population are
determined in a predictable way by the allelic frequencies
(genotypic-frequency equilibrium).
3. The equilibrium is neutral. That is, if it is disturbed, it will
be restored within one generation of random mating at the
new allelic frequencies (if all the other requirements are
maintained)
Calculating Allelic Frequencies
 Assumptions of Hardy-Weinberg
Equilibrium
1.Random Mating
• The first assumption is random mating, which
means that the probability that two genotypes will
mate is the product of the frequencies (or
probabilities) of the genotypes in the population. If
the MM genotype makes up 90% of a population,
then any individual has a 90% chance (probability
0.9) of mating with a person with an MM genotype.
The probability of an MM by MM mating is (0.9)
(0.9), or 0.81.
 2
Large Population Size
• A large population produces a large sample of successful
gametes
• The larger the sample, the greater the probability that the
allelic frequencies of the offspring will accurately
represent the allelic frequencies in the parental population
• When populations are small or when alleles are rare,
changes in allelic frequencies take place due to chance
alone. These changes are referred to as random genetic
drift, or just genetic drift
 3
No Mutation or Migration
• Allelic and genotypic frequencies may change
through the loss or addition of alleles through
mutation or migration (immigration or
emigration) of individuals from or into a
population.
 4
No Natural Selection
• The final assumption necessary to the Hardy-
Weinberg equilibrium is that no individual will
have a reproductive advantage over another
individual because of its genotype
• In other words, no natural selection is occurring
• Artificial selection, as practiced by animal and
plant breeders, will also perturb the Hardy-
Weinberg equilibrium of captive populations
 Proof of Hardy-Weinberg Equilibrium

• The three properties of the Hardy-Weinberg

equilibrium are that
1. Allelic frequencies do not change from
generation to generation
2. Allelic frequencies determine genotypic
frequencies, and
3. The equilibrium is achieved in one generation
of random mating
 Example
• In a population of individuals segregating the
A and a alleles at the A locus, each individual
will be one of three genotypes: AA, Aa, or aa
• If p f(A) and q f(a), then we can predict the
genotypic frequencies in the next generation
• If all the assumptions of the Hardy-Weinberg
equilibrium are met, the three genotypes
should occur in the population in the same
frequencies at which gametes would be
randomly drawn in pairs from a gene pool
Figure: Gene pool concept of zygote formation. Males and females
have the same frequencies of the two alleles: f (A) p and f (a) q
After one generation of random mating, the three genotypes, AA,
Aa, and aa, have the frequencies of p2, 2pq, and q2, respectively
Table: Proportions of Offspring in a Randomly Mating
Population Segregating the A and a Alleles at the A locus:
X f(AA), Y f(Aa), and Z f(aa)
• Before random mating, the frequency of the A
allele is, by definition, p:

• The frequency of the A homozygote is p2, and the

frequency of the heterozygote is 2pq
• Thus, the frequency of the A allele, the frequency
of its homozygote plus half the frequency of the
heterozygotes, is
EXTENSIONS OF HARDY WEINBERG EQUILIBRIUM

 The Hardy-Weinberg equilibrium can be

extended to include, among other cases,
multiple alleles and multiple loci.
MULTIPLE ALLELES
MULTINOMIAL EXPANSION

 If males and females each have the same two alleles

in the proportions of p and q, then genotypes will be
distributed as a binomial expansion in the frequencies
p2, 2pq, and q2 . To generalize to more than two
alleles, one need only add terms to the binomial
expansion and thus create a multinomial expansion.
Conti…
For example, with alleles a, b, and c with frequencies
p, q, and r, the genotypic distribution should be (p +q
+r)2, or
P2 + q2 + r2 + 2pq +2pr + 2qr
Homozygotes will occur with frequencies p2, q2, and
r2, and heterozygotes will occur with frequencies 2pq,
2pr, and 2qr.The ABO blood-type locus in human
beings is an interesting example because it has
multiple alleles and dominance.
Example
The ABO locus has three alleles: IA, IB, and i,
with the IA and IB alleles co dominant, and both
dominant to the i allele. These alleles control
the production of a surface antigen on red
blood cells.
ABO BLOOD-TYPE DISTRIBUTION IN 500
PERSONS FROM MASSACHUSETTS

Blood Type Genotype Number

A I AI A or I Ai 199
B I BI B or I Bi 53
AB I AI B 17
O ii 231
Total 500
CONTI…
 One procedure follows. Let us assume that p =f(IA),
q= f(IB), and r= f(i). Blood type O has the ii genotype;
if the population is in Hardy-Weinberg proportions,
this genotype should occur at a frequency of r2. Thus
f(ii) = 231⁄500 = 0.462 = r2
and
r =f(i) = √0.462 = 0.680
CONTI…
From table we see that blood type A plus blood type O include
only the genotypes I AI A, I Ai, and ii. If the population is in
Hardy-Weinberg proportions, these together should be (p +r)2,
in which p2 =f(I AI A), 2pr =f(I Ai), and r2= f(ii):
( p + r)2 =(199 +231)/500 =0.860
Then, taking the square root of each side
p + r =√0.860 =0.927
and
p = 0.927 − r = 0.927 −0.680= 0.247
CONTI…
The frequency of allele I B, q, can be obtained by similar logic
with blood types B and O, or simply by subtraction:
 Thus, the Hardy-Weinberg equilibrium can be extended to
include multiple alleles and can be used to make estimates of the
allelic frequencies in the ABO blood groups. With ABO, it is
statistically feasible to do a chi-square test because there is one
degree of freedom (number of phenotypes − number of alleles=
4−3=1).We are really testing only the AB and B categories;
if we did our calculations as shown, the observed and expected
values of phenotypes A and O must be equal.
MULTIPLE LOCI
The Hardy-Weinberg equilibrium can also be
extended to consider several loci at the same time in
the same population. This situation deserves mention
because the whole genome is likely involved in
evolutionary processes and we must, eventually,
consider simultaneous allelic changes in all loci
segregating alleles in an organism.
CONTI…
 When two loci, A and B, on the same
chromosome are in equilibrium with each
other, the combinations of alleles on a
chromosome in a gamete follow the product
rule of probability.
CONTI…
Consider the A locus with alleles A and a and the B
locus with alleles B and b, respectively, with allelic
frequencies pA and qa for A and a, respectively, and pB
and qb for B and b, respectively. Given completely
random circumstances, the chromosome with the A
and B alleles should occur at the frequency pA pB.
This is referred to as linkage equilibrium.
CONTI…
• When alleles of different loci are not in
equilibrium (i.e., not randomly distributed in
gametes), condition is referred to as linkage
disequilibrium. The approach to linkage
equilibrium is gradual and is a function of the
recombination distance between the two loci.
EXAMPLE
For example, let’s start with a population out of equilibrium so
that all chromosomes are AB (70%) or ab (30%). Then pA =0.7,
qa = 0.3, pB =0.7, and qb=0.3. We expect the Ab chromosome to
occur 0.7 ×0.3 = 0.21, or 21% of the time. The frequency of the
Ab chromosome is zero.
 Assume the map distance between the two loci is 0.1; in other
words, 10% of chromatids in gametes are recombinant.
 Initially, we consider that each locus is in Hardy-Weinberg
proportions, or the frequency of AB/AB individuals =0.49 (0.7
×0.7); the frequency of ab /ab individuals is 0.09 (0.3 × 0.3);
and the frequency of AB/ab individuals is 0.42 (2 ×0.7 ×0.3).
CONTI…
 After one generation of random mating, gametes will be as
follows:
from AB/AB individuals (49%): only AB gametes, 49% of total
from ab/ab individuals (9%): only ab gametes, 9% of total
from AB/ab individuals (42%):
AB gametes, 18.9% of total (0.45 ×0.42)
ab gametes, 18.9% of total (0.45 ×0.42)
Ab gametes, 2.1% of total (0.05 ×0.42)
aB gametes, 2.1% of total (0.05× 0.42)
CONTI…
(The values of 18.9% and 2.1% for the dihybrids
result from the fact that since map distance is 0.1,
10% of gametes will be recombinant, split equally
between the two recombinant classes—5% and 5%.
Ninety percent will be parental, split equally
between the two parental classes—45% and 45%.
Each of these numbers must be multiplied by 0.42
because the dihybrid makes up 42% of the total
number of individuals.)
 CONTI…
Although we expect 21% of the chromosomes to be
of the Ab type, only 2.1%, 10% of the expected,
appear in the gene pool after one generation of
random mating.
 You can see that linkage equilibrium is achieved at
a rate dependent on the map distance between loci.
Unlinked genes, appearing 50 map units apart, also
gradually approach linkage equilibrium.
CONTI…
If the frequencies of alleles at an autosomal locus
differ in the two sexes, it takes two generations of
random mating to achieve equilibrium.
In the first generation, the allelic frequencies in the
two sexes are averaged so that each sex now has the
same allelic frequencies. Genotypic frequencies then
come into Hardy-Weinberg proportions in the second
generation.
CONTI…
However, if the allelic frequencies differ in the two sexes for a sex-
linked locus, Hardy-Weinberg proportions are established only
gradually.
The reasoning is straightforward. Females, with an X chromosome
from each parent, average the allelic frequencies from the previous
generation.
However, males, who get their X chromosomes from their mothers,
have the allelic frequencies of the females in the previous generation.
 Hence, the allelic frequencies are not the same in the two sexes after
one generation of random mating, and equilibrium is achieved
slowly.