Last Update: 2 November 2017 Part-I

The Hardy-Weinberg equilibrium M-18

Process of evolutionary change
Evolutionary change affects all aspects of living things their morphology, physiology, behavior and
ecology. Underlying these changes there are genetic changes, which in interaction with the environment
determine what the organisms are. At the genetic level, evolution consists of changes in the genetic of
population.
Evolution can occur if there is hereditary variability. The ultimate source of all hereditary variations is
mutation and such variability is sorted out by independent assortment and recombination. Apparently it might
appear that individuals exhibiting a dominant genotype should be more common then individuals with a
recessive phenotype. But it must be remembered that a 3:1 ratio occur in the offspring of two individuals,
heterozygous for the same two allele. Entirely different ratios would occur in other mating combination and
the frequencies of these combinations would depend on the genotype frequencies in a population.
So the question comes how we can determine the frequencies of genotype in a population?
Mendelism does not tell us anything about the genotype frequencies. Unlike the expected 3:1
frequencies of a dominant allele brachydactyly occurs at a very low frequency in the population. The first
demonstration that gene frequencies are not dependent upon dominance or recessive, but may remain
essentially unchanged from one generation to the next under certain conditions, was independently show by
the English mathematician G.H. Hardy and the German physician W. Weinberg in 1908.
Hardy-Weinberg Law: The main statement in Hardy-Weinberg law is that, in the absence of any
evolutionary processes (Mutation, migration, drift & selection) gene frequencies remain constant from
generation to generation.
The assumptions specify an ideal population that free of many of the complications that affect real
population.
1. Individual of all genotypes have equal rates survival and equal reproductive success. That is there
is no selection.
2. There are no mutations that create new allele or convert one allele into other.
3. There is no migration of individuals into or out of the population.
4. The population is infinitely large, which in practical terms means that the population is large
enough that sampling errors and other random effects are negligible.
5. The individuals in the population mate at random
The Hardy-Weinberg law demonstrated that a population confirming to these assumptions has the
following properties.
1. The allele frequencies in the population do not change from generation to generation; in other
words, the population does not evolve.
2. After one generation of random mating, the genotype frequency can be predicted from the allele
frequencies
A model in which allele frequencies do not change from one generation to the next may not seem like a
promising tool for the study of evolution. What makes the Hardy-Weinberg law useful, however, is the explicit
assumption on which it is based. By specifying ideal condition under which allele frequencies will not change,
the Hardy-Weinberg law identifies the real world forces that can cause allele frequencies to change. In other
words, the Hardy-Weinberg law identifies the forces of evolution.

What are gene frequencies and genotype frequencies?

As a species we are characterized by many traits; most of us are tall, two eyed, five-fingered etc. But
there are people who are short, some are albino, some has six (6) fingers. But gene causing five fingers are
more common / more frequent than those causing six fingers or more.
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 A preliminary step in analyzing the genetics of a population is to measure gene or allele frequencies.
The allele frequencies of all gene loci would define a species precisely and knowledge of how these frequencies
change is tantamount to the knowledge of how evolution can occur.
What is equilibrium?
We will now have to investigate whether there are many spontaneous possibilities of these allele
frequencies to change, because evolution involves the alteration of allele frequencies. For this let us take our
population and allow forming another generation. Assuming a random mating, the frequency of a given
genotype will simply be a product of the frequencies of the two corresponding alleles.
The total genotypes of the next generation will be therefore 0.49 blood group of M.
0.21 + 0.21 = 0.42 group of MN and 0.09 group of N.
LM bearing LN bearing (0.3)
=q
(0.7) = P
LM bearing (0.7) = p LMLM Zygote LMLN zygote
(0.49) = p2 (0.21) = pq
LN bearing (0.3) = q LNLM zygote LNLN zygote
(0.21) = pq (0.09) = q2
In other words there will be no change in either gene or genotype frequencies from one generation to
the next: this is an equilibrium situation. It is called a Hardly-Weinberg equilibrium.
Hardy-Weinberg Equilibrium (HWE) is defined by a set of genotypic frequencies of p2 AA. 2pq Aa
q2
and aa in which A and a represents alleles at any locus and (p+q) are the frequencies of A and a. If the
ratio of AA : Aa : aa is p2 : 2pq : q2 then the population is in HWE and the allele and genotype frequencies do
not change from one generation to the next.
To show that this is not just a trick of number we can use the same allele frequencies but non-HWE
genotype frequencies. See the consequence from one generation to the next.

Take for example, a population of 45M, 50 MN and 5 N blood group, here, P = .45 + 1/ 2 X 50 = .45
+ .25 = .70 (or70%) and q = 0.3 (or 30%). When these allele frequencies will be used in random mating we
will be again obtain as 0.49 LMLM, 0 .42 LMLN and 0.09 LNLN

So this time we do have a change: our 45:50:5 ratio becomes a 49:42:9 ratio in one generation. The
original population is obviously not in equilibrium.
If a population is not in equilibrium than it takes only one generation of random mating to establish
Hardy-Weinberg Equilibrium.

What is allele frequency?

Theoretically it is very simple to measure allele frequency. One simply look at the population, assumes
that each person is just one cell and count how many alleles of each kind there are, for controlling MN blood
group. People are M, MN or N of the genotypes LMLM, LMLN and LNLN at the L locus respectively. All these
genotypes can be identified directly (genotype = phenotype).

Suppose, in a sample of 100 people, 49 are of M blood group, 42 of MN and 9 of N (Table 1).
TABLE 1
Blood Group Genotype # people # LM alleles #LN Alleles
M LMLM 49 98 -
MN LMLN 42 42 42
N LNLN 9 18
100* 140 60
Total # allele 200*
* The allele No always will be seen from Table 1 that there are in table, 200 LM + LN or 200L alleles, of them
140/ 200 = 0.7 or (70%) are LM and 60 / 200 = 0.3 or (30%) that are LN. This can also be calculated by the
following formula.
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Gene frequency = frequency of homozygotes + 1/ 2 of heterozygotes.
P = 49 +1/ 2 of 42
= 49 +21
= 70% or .70
If there are only two alleles at a particular locus their frequencies are generally called p and q. Let us
call p as the frequency of LM and q that LN (p is usually given to the dominant allele) in our example, p + q
= 0.7 + 0.3 = 1.0. One important point to notice here is that, the ratios associated with families just dont show
up in the population. We should not expect at 1:2:1 of M : MN : N ratio, because that is depicted from only a
MN X MN marriage. We has all probable mating in our population; which are,
1. MM X MN = MM : MN
2. MM X MM = all MM
3. MM X NN = all MN
4. NN X NN = all NN
5. NN X MN = NN : MN
6. MN X MN = MM : MN : NN
1 2 1
Another example:
If we mate two individuals that are heterozygous (e.g., Bb) for a trait, we find that
25% of their offspring are homozygous for the dominant allele (BB)
50% are heterozygous like their parents (Bb) and
25% are homozygous for the recessive allele (bb) and thus, unlike their parents, express the recessive
phenotype.
This is what Mendel found when he crossed monohybrids. It occurs because
Meiosis separates the two alleles of each heterozygous parent so that 50% of the gametes will carry one
allele and 50% the other.
When the gametes are brought together at random, each B (or b)-carrying egg will have a 1 in 2
probability of being fertilized by a sperm carrying B (or b). (Left table)
Results of random union of the two gametes produced by
Results of random union of the gametes
two individuals, each heterozygous for a given trait. As a
produced by an entire population with a
result of meiosis, half the gametes produced by each
gene pool containing 80% B and 20% b.
parent with carry allele B; the other half allele b.
0.5 B 0.5 b 0.8 B 0.2 b
0.5 B 0.25 BB 0.25 Bb 0.8 B 0.64 BB 0.16 Bb
0.5 b 0.25 Bb 0.25 bb 0.2 b 0.16 Bb 0.04 bb

But the frequency of two alleles in an entire population of organisms is unlikely to be exactly the same. Let us
take as a hypothetical case, a population of hamsters in which
80% of all the gametes in the population carry a dominant allele for black coat (B) and
20% carry the recessive allele for gray coat (b).
Random union of these gametes (right table) will produce a generation:
64% homozygous for BB (0.8 x 0.8 = 0.64)
32% Bb heterozygotes (0.8 x 0.2 x 2 = 0.32)
4% homozygous (bb) for gray coat (0.2 x 0.2 = 0.04)
So 96% of this generation will have black coats; only 4% gray coats.
Will gray coated hamsters eventually disappear?

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No. Let's see why not.
All the gametes formed by BB hamsters will contain allele B as will
one-half the gametes formed by heterozygous (Bb) hamsters.
So, 80% (0.64 + .5*0.32) of the pool of gametes formed by this generation with contain B.
All the gametes of the gray (bb) hamsters (4%) will contain b but
one-half of the gametes of the heterozygous hamsters will as well.
So 20% (0.04 + .5*0.32) of the gametes will contain b.
So we have duplicated the initial situation exactly. The proportion of allele b in the population has remained
the same. The heterozygous hamsters ensure that each generation will contain 4% gray hamsters.
Now let us look at an algebraic analysis of the same problem using the expansion of the binomial (p+q)2.
(p+q)2 = p2 + 2pq + q2
The total number of genes in a population is its gene pool.
Let p represent the frequency of one gene in the pool and q the frequency of its single allele.
So, p + q = 1
o p2 = the fraction of the population homozygous for p
o q2 = the fraction homozygous for q
o 2pq = the fraction of heterozygotes
In our example, p = 0.8, q = 0.2, and thus
(0.8 + 0.2)2 = (0.8)2 + 2(0.8)(0.2) + (0.2)2 = 064 + 0.32 + 0.04
The algebraic method enables us to work backward as well as forward. In fact, because we chose to make B
fully dominant, the only way that the frequency of B and b in the gene pool could be known is by determining
the frequency of the recessive phenotype (gray) and computing from it the value of q.
q2 = 0.04, so q = 0.2, the frequency of the b allele in the gene pool. Since p + q = 1, p = 0.8 and allele B makes
up 80% of the gene pool. Because B is completely dominant over b, we cannot distinguish the Bb hamsters
from the BB ones by their phenotype. But substituting in the middle term (2pq) of the expansion gives the
percentage of heterozygous hamsters. 2pq = (2)(0.8)(0.2) = 0.32
So, recessive genes do not tend to be lost from a population no matter how small their representation.
So long as certain conditions are met (to be discussed next),
gene frequencies and genotype ratios in a randomly-breeding population remain constant from generation to
generation.
This is known as the Hardy-Weinberg law in honor of the two men who first realized the significance of the
binomial expansion to population genetics and hence to evolution.
Evolution involves changes in the gene pool. A population in Hardy-Weinberg equilibrium shows no change.
What the law tells us is that populations are able to maintain a reservoir of variability so that if future
conditions require it, the gene pool can change. If recessive alleles were continually tending to disappear, the
population would soon become homozygous. Under Hardy-Weinberg conditions, genes that have no present
selective value will nonetheless be retained.
When the Hardy-Weinberg Law Fails to Apply
To see what forces lead to evolutionary change, we must examine the circumstances in which the Hardy-
Weinberg law may fail to apply. There are five:
mutation
gene migration
genetic drift
nonrandom mating
natural selection
Mutation
The frequency of gene B and its allele b will not remain in Hardy-Weinberg equilibrium if the rate of mutation
of A -> a (or vice versa) changes.
By itself, mutation probably plays only a minor role in evolution; the rates are simply too low.
But evolution absolutely depends on mutations because this is the only way that new alleles are created. After
being shuffled in various combinations with the rest of the gene pool, these provide the raw material on which
natural selection can act.

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Gene Migration
Many species are made up of local populations whose members tend to breed within the group. Each local
population can develop a gene pool distinct from that of other local populations.
However, members of one population may breed with occasional immigrants from an adjacent population of
the same species. This can introduce new genes or alter existing gene frequencies in the residents.
In many plants and some animals, gene migration can occur not only between subpopulations of the same
species but also between different (but still related) species. This is called hybridization. If the hybrids later
breed with one of the parental types, new genes are passed into the gene pool of that parent population. This
process, is called introgression. It is simply gene migration between species rather than within them.
In either case, gene immigration increases the variability of the gene pool.
Genetic Drift
As we have seen, interbreeding often is limited to the members of local populations. If the population is small,
Hardy-Weinberg may be violated. Chance alone may eliminate certain members out of proportion to their
numbers in the population. In such cases, the frequency of an allele may begin to drift toward higher or lower
values. Ultimately, the allele may represent 100% of the gene pool or, just as likely, disappear from it.
Drift produces evolutionary change, but there is no guarantee that the new population will be more fit than
the original one. Evolution by drift is aimless, not adaptive.
Nonrandom Mating
One of the cornerstones of the Hardy-Weinberg equilibrium is that mating in the population must be random.
If individuals (usually females) are choosy in their selection of mates the gene frequencies may become altered.
Darwin called this sexual selection.
Nonrandom mating seems to be quite common. Breeding territories, courtship displays, "pecking orders" can
all lead to it. In each case certain individuals do not get to make their proportionate contribution to the next
generation.
Assortative mating
Humans seldom mate at random preferring phenotypes like themselves (e.g., size, age, ethnicity). This is called
assortative mating.
Marriage between close relatives is a special case of assortative mating. The closer the kinship, the more alleles
shared and the greater the degree of inbreeding. Inbreeding can alter the gene pool. This is because it
predisposes to homozygosity. Potentially harmful recessive alleles - invisible in the parents - become exposed
to the forces of natural selection in the children.
It turns out that many species - plants as well as animals - have mechanisms be which they avoid inbreeding.
Examples:
Link to discussion of self-incompatibiity in plants.
Male mice use olfactory cues to discriminate against close relatives when selecting mates. The
preference is learned in infancy - an example of imprinting. The distinguishing odors are
o controlled by the MHC alleles of the mice;
o detected by the vomeronasal organ (VNO).
Natural Selection
If individuals having certain genes are better able to produce mature offspring than those without them, the
frequency of those genes will increase. This is simple expressing Darwin's natural selection in terms of
alterations in the gene pool. (Darwin knew nothing of genes.) Natural selection results from
differential mortality and/or
differential fecundity.
Mortality Selection
Certain genotypes are less successful than others in surviving through to the end of their reproductive period.
The evolutionary impact of mortality selection can be felt anytime from the formation of a new zygote to the
end (if there is one) of the organism's period of fertility. Mortality selection is simply another way of describing
Darwin's criteria of fitness: survival.
Fecundity Selection
Certain phenotypes (thus genotypes) may make a disproportionate contribution to the gene pool of the next
generation by producing a disproportionate number of young. Such fecundity selection is another way of
describing another criterion of fitness described by Darwin: family size.
In each of these examples of natural selection certain phenotypes are better able than others to contribute their
genes to the next generation. Thus, by Darwin's standards, they are more fit. The outcome is a gradual change
in the gene frequencies in that population.

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Calculating the Effect of Natural Selection on Gene Frequencies.
The effect of natural selection on gene frequencies can be quantified. Let us assume a population containing
36% homozygous dominants (AA)
48% heterozygotes (Aa) and
16% homozygous recessives (aa)
The gene frequencies in this population are
p = 0.6 and q = 0.4
The heterozygotes are just as successful at reproducing themselves as the homozygous dominants, but the
homozygous recessives are only 80% as successful. That is, for every 100 AA (or aa) individuals that reproduce
successfully only 80 of the aa individuals succeed in doing so. The fitness (w) of the recessive phenotype is thus
80% or 0.8.
Their relative disadvantage can also be expressed as a selection coefficient, s, where
s=1-w
In this case, s = 1 - 0.8 = 0.2.
The change in frequency of the dominant allele (delta p) after one generation is expressed by the equation p
sp0 q 02
=
1 - sq 02
where p0 and q0 are the initial frequencies of the dominant and recessive alleles respectively. Substituting, we
get
(0.2)(0.6)(0.4) 2 0.019
p= 2
= = 0.02
1 - (0.2)(0.4) 0.968
So, in one generation, the frequency of allele A rises from its initial value of 0.6 to 0.62 and that of allele a
declines from 0.4 to 0.38 (q = 1 - p).
The new equilibrium produces a population of
39.7% homozygous dominants (an increase of 3.7%) (p2 = 0.397)
46.6% heterozygotes (a decline of 1.4%)(2pq = 0.466) and
13.7% homozygous recessives (a decline of 2.3%)(q2 = 0.137)
If the fitness of the homozygous recessives continues unchanged, the calculations can be reiterated for any
number of generations. If you do so, you will find that although the frequency of the recessive genotype
declines, the rate at which a is removed from the gene pool declines; that is, the process becomes less efficient
at purging allele a. This is because when present in the heterozygote, a is protected from the effects of
selection.

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Suggested problems (from Strickberger) and answers

Q.1. In a large randomly mating population of snakes, 75% of individuals at birth have black stripes and 25%
lack of such stripes. Explain whether this indicates that black stripes are dominant.
Ans:- The percentage given in the problem are phenotypic frequencies in the population and not ratios
produced by the a particular set of crosses. Thus it is entirely possible that blank stripes are caused by a receive
allele whose frequency (a) is 0.75 = 0.87, and the absence of such stripes caused by a dominant allele whose
frequency (p) is 1-0.87 = 0.13. Mind that a dominant allele need not be present in high frequency.
Q.2. What is the frequency of heterozygotes Aa in a randomly mating population if the frequency of
recessive phenotype (aa) is 0.09?
Ans:- As the population is panmictic (Randomly mating)
So, we can consider/ assume that the population is in Hardy Weinberg equilibrium,
So, frequency of aa = 0.09 AA = p2
Or, pq2 = 0.09 where p = frequency of dominant allele and
Or, q = 0.3 q = frequency of recessive allele Aa = 2pq
Hence p = (1- 0.3) = 0.7 aa = q2
So, the frequency of heterozygotes will be 2pq = 2 0.3 0.7 = 0.42
Q.3. What is the frequency of heterozygotes Aa in a random mating population in which the frequency of
all dominant phenotype is 0.19?
Ans: Population is random-mating, so it is in Hardy-Weinberg equilibrium.
Now, p2 + 2pq = 0.19
Hence, q2 = 1- 0.19 [As P2 + 2pq + q2 = 1]
= 0.81
or, q = 0.81
= 0.9
Now, p = 1- q = 1- 0.9 = 0.1

Therefore frequency of heterozygotes will be 2pq

or, 2 0.1 0.9 = 0.18
[And frequency of dominant homozygotes (AA) will be
p2 = (0.1)2 = 0.01]
Q.4. Two population begin with the following genotype frequencies.
Popn-I: 0.24 (AA) 0.32 (Aa) 0.44 (aa)
Popn-II: 0.33 (AA) 0.14 (Aa) 0.53 (aa)
If random mating occurs what will be their genotypic frequencies in the next generation?
Ans:- Consider q = frequency of recessive allele
p = frequency of dominant allele

For popn- I p = 0.24 + 0.32

= 0.24 +0.16 = 0.4
q = 1-0.4 = 0.6
For popn- II p = 0.33 + 0.14
= 0.33 +0.07 = 0.4
q = 1-0.4 = 0.6
Hence, the equilibrium genotype frequencies will be
P2 (AA), 2pq (Aa) q2 (aa)
Or 0.16 AA 0.48 Aa 0.36 aa
___ if the random mating occur.

Q.5. (a) Which of the following population are in Hardy-Weinberg equilibrium?

Production Genotype frequency.
AA Aa aa
I 0.43 0.418 0.089
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 II 0.64 0.32 0.04
III 0.4225 0.4550 0.1225
IV 0.0025 0.1970 0.8005
V 0.0081 0.0828 0.9091

(b) What are the expected equilibrium frequencies for those of the above population that re not in
equilibrium?
(c) How long will it take for these equilibrium values to be reached under random mating?
Ans: (Hints)
In each ease, first, calculate the p and a.
1
p = frequency of AA + frequency of Aa
2
1
q = 1 p [or, frequency of aa + frequency of Aa]
2
Then calculate the expected equilibrium frequency
AA Aa aa
i.e. 2
p 2pq q 2
How, compare the expected equilibrium frequency and observed frequencies that are given in the problem.
Now, if the values appears identical then infer that the population is in equilibrium if the values are different
then conclude that the population is not in equilibrium and it will take only one generation to reach
equilibrium if random mating takes place.
Example for population II
AA Aa aa
II 0.64 0.32 0.04
Let, frequency of dominant allele (A) = p
And frequency of recessive allele (a) = q
1
P = 0.64 + 0.32 = 0.64 + 0.16 = 0.8
2
q = (1 0.8) = 0.2
So, Expected equilibrium frequency = p2(AA), 2pq (Aa), q2 (aa)
= 0.64 (AA), 0.32 (Aa), 0.04 (aa)
Now, as the observed frequency and expected equilibrium frequency is same, Hence the population is in
equilibrium.
[Note: The genotypic frequencies that are mentioned in the question / problem is called observed frequency
and the calculated frequency (p2, 2pq, q2) are the expected equilibrium frequency as it demotes the
frequencies after one generation. And we know that if random mating occur after one generation any
population must reach in equilibrium.]

Ans : (a) Population II and III are in equilibrium.

(b) I 0.450 AA, 0.442 Aa, 0.108 aa.
IV 0.0102 AA, 0.1816 Aa, 0.8082 aa.
V 0.0025 AA, 0.0941Aa, 0.9034 aa
(c) One generation.

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Q.6.
Population AA Aa aa
7 0.25 0.50 0.25
In population 7, the a allele is detrimental as well as the A allele is incompletely dominant, so that AA is
perfectly fit, Aa has a fitness of 0.8 and aa has a fitness of 0.6. If there is no mutation, what will p and q be in
the next generation?

Ans : As AA is perfectly fit so the fitness (W) of this genotypic is 1.

Change in allelic frequency after selection will be as follows

AA (p2) Aa (2pq) aa (q2)

a) Initial genotype frequencies 0.25 0.50 0.25
b) Fitness W11 = 1 W12 = 0.8 W22 = 0.6
c) Frequency after selection p2 x W11 2pq x W12 q2 x W22
= (0.25) (1) = (0.50) (0.80) = 0.25 x 0.6
= 0.25 = 0.40 = 0.15
d) Relative genotype frequency after selection 2
2 pqW12 q 2W22

p W11
* Where W a p 2W11 2 pqW12 q 2W22 p
H Q
*W a Wa Wa
" Mean fitness" 0.25 0.40 0.15
= 0.25 + 0.40 + 0.15
0.80 0.80 0.80
= .80 = .3125 = .50 = .1875
e) Allelic frequency after selection (in the p p 1 H
next generation) 2
.3125 1 .50 .3125 .25 .5625
2
q 1 p 1 .5625 .4375

or Q 1 H .1875 .25 .4375
2

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