Last Update: 4 November 2017 Part- II

M- 22
HARDYWEINBERG EQUILIBRIUM :
Major Influences on Gene frequencies
Ref: Evolution by CJ Avers; Genetics-Strickberger; Genetics-Tamarin
Any locus with allele frequencies in equilibrium is not evolving, because there is no genetic
change over time. Changes in gene frequencies indicate evolution in progress, but changes may take
place at some gene loci and not at other in any population at any time. We will now see how the Hardy
Weinberg theorem can be used to obtain quantitative information on evolutionary processes and how
different factors influence the nature and pace of genetic modification in evolving population.

Mutation and Gene frequencies

One of the causes responsible for a change in gene frequency is the frequency of mutation itself.
Recurrent forward mutation, A a, reduce the frequency of A and increase that of a in the gene pool and
the reverse mutation a A have the opposite effect. The rate of forward mutation, u and the rate of
reverse mutation v, are expressed as proportions of alleles mutating per generation. The actual value of
total alleles of a gene changing from A to a in one generation is p0; from a to A, it is vq0 (when allelic
frequency for A = p0 and for a = q0).
The extent of the mutation effect depends on the initial frequencies of the alleles as well as the
mutation rates, which is implicit in the terms up and vq. The net change in the frequency of A or p is
p = vq up.
The new frequency of allele A or p1 is the sum of initial frequency plus the change in frequency of
A or P1= P0+p (when both forward and backward mutation occur).
For example, if P0 = 0.8 and q0=0.2 and the mutation rate =10-5 and v = 108; then net change in
gene frequency for p (i.e.p) is
p = (10 8 x 0.2) (10 5 x 0.8)
= (2 x 109) (8 x 106)
= 7.998 x 106
= ~ 8 x 106 (rounded off from 7.998 x 106).
The new frequency of allele A (p1) is now
P1 = 0.8 + (8 x 106)
= 0.799992
and, q1 = 0.200008
The net effect of mutation in one generation in this case is only eight more a alleles (and eight
fewer A) per million gametes making up the gene pool for the new generation.
The allele frequency ultimately reach an equilibrium when no further changes occurs as the result
of mutation alone. This is expressed as
p = up vq = 0
or u p = v q ( where p and q are the equilibrium frequencies of A and a respectively).
The equilibrium frequency of the two alleles can be determined by
u p = v q
or, u p = v (1 p ) [as p+q =1]
or, u p = v v p
or, p (u + v ) = v
v
or, p =
uv
-1-
 u
Similarly q =
uv
The equilibrium value p and q thus depend on only the mutation rates and are independent of
the initial frequency p0 and q0, including 0 to 1. The time at which the allele reach equilibrium will vary
of course, according to their particular starting frequencies. In this example the stable equilibrium
frequencies will be p = 0.001 and q = 0.999. It will take many tens of thousands of generations, however,
before these frequencies become established under the influence of mutation alone.
But when only forward mutation (Aa) occurs at the rate of u, then after one generation the
appearance of a in a frequency of up0. In other words, the frequency of A is now reduced to
p0up0=p0(1u). In the next generation now a genes arise is the frequency u [p0 (1u)] = p0(uu2); so the
frequency of A is now
[p0 (1u)] [p0 (u u2]
= p0 p0up0u + p0u2 = p0 2 p0u + p0u2
= p0 (1u)2
As the number of generation increases to n, the frequency of A becomes equal to p0(1u)n. Thus,
even if the mutation rate of A to a is small, after a large enough number of generations the term (1u)n
will approach zero and A will disappear. However, the mutation rate does not always occur in only one
direction.
It can these be seen that a selectively neutral allele can become fixed in the gene pool as the
consequence of mutation but the process is very slow in large, randomly mating populations not
undergoing gene flow. Mutation is regarded as a relatively weak force in evolution because of the slow
pace of changes effected. But mutation is the primary means by which most new genetic information is
produced and many alleles may exist for a gene locus because each nucleotide substitution may give rise
to a new gene sequence. The rate of forward mutation is much higher than the rate of reverse mutation
back to the original sequence, so any allele can be rare but many different allele may exist in the gene
pool. The reservoir of allele diversity produce greater evolutionary flexibility in populations over the long
run of time and in changing environments.

The Effects of Selection on Gene Frequencies :

One of the most important cause for the change in gene frequency of an allele lies in the allele of
its carriers to produce surviving offspring. It is obvious that if individuals carrying the gene A are more
successful in reproduction than individuals carrying its allele a, the frequency of the former will tend to
be greater than that of the latter. The wide variety of mechanisms responsible for modifying the
reproductive success of a genotype is known collectively as selection. It is important to remember that
selection acts on whole organisms and thus on phenotypes. However, we analyze the process by looking
directly as the genotype, usually only at one locus.
Suppose we start with a population of zygotes (fertilized eggs) of known genotypes, which are
present in the frequencies of 0.25 AA, 0.50 Aa and 0.25 aa. The allele frequencies are p 0=q0=0.5 in this
initial generation. We observe the survival and reproduction of each genotype class and find that for
every 100 AA or Aa zygotes that survive and reproduce, only 80 aa zygotes survive and reproduce. These
genotype can be described in terms of fitness (W) which is the ability to survive and reproduce and of
selective disadvantage, which is reduction in fitness, represented by the selection coefficient (s). If the
fitness of AA and Aa is set at 1 (100%) then the relative fitness of the genotype aa is only 0.8(80%) of
this level. The formula for determining fitness is
W = 1 s , and for the aa genotype
0.8 = 1 s or s = 0.2
[A selection coefficient measures the sum of force acting to prevent reproductive success.]
The allele frequencies in the gene pool of the next generation will be different from that of the
initial generation, because all the AA and Aa genotypes but only a fraction of the aa genotypes contribute
to the gene pool. (Table1). The new allele frequencies p1 (A) and q1 (a), will differ from the initial
frequencies p0 (A) and q0 (a); but the sum of their frequencies remain 1. Once the new value of p is
known, q can be obtained from 1 p.
The changes in p (or p), is obtained with the formula.
-2-
 sp0 q 02
p =
1 - sq 02
Table 1

Genotype Initial Frequency Fitness (W) Contribution to the Gene pool

AA 0.25 1 1 x 0.25 = 0.25
Aa 0.50 1 1 x 0.50 = 0.50
aa 0.25 0.8 0.8 x 0.25 = 0.18
0.93

Genotype Relative Genotype frequency Allelic frequency after

after selection selection
AA 0.25 / 0.93 = 0.269 P1 = 0.269 + ( 0.538)
= 0.269 + 0.269
= 0.538
Aa 0.50 / 0.93 = 0.538 q1 = 0.193 + (0.538)
aa 0.18 / 0.93 = 0.193 = 0.462
1.000

p = p1 p0 = 0.538 0.500 =+ 0.038

q = q1 q0 = 0.462 0.500 = 0.038

Selection against the Recessive homozygote

We can analyze selection by using the standard model building protocol of population genetics-
namely, define the initial conditions; allow selection to act, calculate q (change in gene frequency from
one generation to the next); then calculate equilibrium frequency q when q becomes zero and examine
the stability of the equilibrium. In the analysis, we consider a single autosomal locus in a diploid,
sexually reproducing species with two alleles and assume that selection acts directly on the phenotypes in
a simple fashion. After selection the individuals remaining within the population mate at random to form
a new generation in Hardy-Weinberg proportions.

Selection Model
In the model (in the following table) the dominant homozygote and the heterozygote have the
same fitness (W = 1). Natural selection cannot differentiate between the two genotypes because they both
have the same phenotype. The recessive homozygote, however is being selected against which means that
it has a lower fitness than the two other genotypes (W = 1 s)
After selection, the ratio of the different genotypes is determined by multiplying their frequency
by their fitness.
Genotype Total
AA Aa aa
Initial genotype frequency p2 2pq q2 1
Fitness (W) 1 1 1s
Ratio after selection p 2
2pq q (1s)
2
1 sq 2 W
Genotype frequency after selection p2 2pq q 2 1 s 1
1 sq 2 1 sq 2
1 sq 2
The value (1 sq2) is referred to as the mean fitness of population, W , because it is the sum of
the fitness of the genotype multiplied (weighted) by the frequency at which they occur. Thus, it is a
weighted mean of the fitnesses weighted by their frequencies. The new ratios of the three genotypes can
be returned to genotypic frequencies by simply dividing by the mean fitness of the population ( W ) .The

-3-
new genotypic frequencies are thus the products of their original frequencies times their fitness, divided
by the mean fitness of the population.
After selection the new allelic frequency for successive allele (qn+1) is the proportion of aa
homozygotes plus half the proportion of heterozyotes, or
q 2 1 s pq q 2 sq 2 pq
q1 or qn+1 = =
1 sq 2 1 sq 2 1 sq 2
qq sq p
=
1 sq 2
q1 sq
=
1 sq 2
The frequency of dominant allele after selection (p1) can be obtained as

p2 pq
P1 or pn +1 =
1 sq 2
1 sq 2
or p1 = 1-q1
q1 sq p 2 pq
= 1 =
1 sq 2 1 sq 2
1 sq 2 q sq 2 pp q
= =
1 sq 2 1 sq 2
1 q
=
1 sq 2 =
p
As , p q 1
1 sq 2
=
p
As ,1 q p
1 sq 2

Change in allelic frequency for recessive allele

q1 sq
or q = q
1 sq 2

=

q1 sq q 1 sq 2
1 sq 2
q sq 2 q sq 3
=
1 sq 2
sq 2 1 q spq 2
= or
1 sq 2 1 sq 2
spq 2
q =
1 sq 2
Change in allelic frequency for dominat allele or
p
p = p
1 sq 2

=

p p 1 sq 2
1 sq 2
p p spq 2
=
1 sq 2
spq 2
=
1 sq 2

-4-
Selection Against Recessive lethals : -
It we assume that the aa genotype is lethal, its fitness would be zero, and selection coefficient (s)
would be one.
We can now substitute this value of s in the formation.

q1 sq q1 q
q1 =
1 sq 2 1 q2
q1 q q
=
1 q 1 q 1 q
and now q becomes
q
q = q
1 q
q q1 q q 2
=
1 q 1 q

This is the expression for the change in allelic frequency caused by selection. Two facts should be
apparent from this equation :
First :
The frequency of the recessive allele (q) is declining as indicated by negative sign of the fraction
,This fact should be intuitive because of the way selection was defined in the model (eliminating aa
homozygotes).
Second :
The change in allelic frequency proportional to q2, which appears in the numerator of the
expression. In other words, allelic frequency is declining as a relative function of the number of
homozygous recessive individuals in the population. This final formation supports the methodology of
the model.

The amount of change in allelic frequency after a given number of generations become can now
easily be calculated. Representing the frequency of recessive allele initial and following generations by
q0, q1, q2, qt,
We have
q0 q
q1 = and q 2 1
1 q0 1 q1
Substituting the value of q1 in the equation for q2, we get
q0
1 q0 q0
q2 =
q0 1 2q 0
1
1 q0

Similarly after t generation of selection.

q0
qt =
1 tq 0
The number of generation or t (required to change allele frequency from q 0 to qt) can therefore be
determined from a certain value q0 to another qt .
q0
qt =
1 tq 0
or, q0 = qt(1+tq0)
= qt + qt / tq0
or, q0-qt = qt+tq0= t (q0qt)
-5-
 q 0 qt 1 1
or, t =
q 0 qt qt q 0
This formula becomes much more easier when we want to know the however of generation (t) that are
required to reduce the existing q to its half [ i.e. when qt = q0/2 ]

1 1
t =
q0 2 q0
2 1 1
=
q0 q0 q0
Equilibrium Condition :
We can calculate the equilibrium q by setting the q equation equal to zero, since a population in
equilibrium will show no change in allele frequencies from one generation to next :
q2
0
1 q
For a friction to be zero, the numerator must equal to zero.
Thus, q2 = 0 and q^ = 0
At equilibrium, the a allele should be entirely removed from the population. If aa homozygotes are being
removed, and if there is no mutation to return a allele to the population, then eventually the a allele
disappears from the population.
Selection Mutation Equilibrium :
Although a deleterious alleles is eliminated slowly from a population the time frame is so great
that there is opportunity for mutation to bring the allele back. Given a population, in which alleles are
removed by selection and added by mutation, the point at which no change in allelic frequency occurs,
the selection mutation equilibrium, may be determined as follows.

The new frequency (qn + 1) of the recessive a allele after nonlethal selection (s<1) against homozygote is
obtained by equation :
q1 sq
qn 1
1 sq 2
Change in allelic frequency under this circumstance will thus be
sq 2 1 q
q =
1 sq 2
The change in allelic frequency due to mutation can be found by using the equation :
q = up vq.
Where u and v are the rate of forward and back mutation, respectively when equilibrium exists, the
change from selection will just balance the change from mutation. Thus,
sq 2 1 q
up vq 0
1 sq 2
and
sq 2 1 q
up vq
1 sq 2
Now, some judicious simplifying is justified, because in a real situation, q will be very small because the
a allele is being selected against. Thus, vq will be close to zero, and 1-sq2 will be close to unity. Thus,
the previous equation becomes :
up sq2 (1 q)
or u (1 q) sq2 (1 q)
or q2 u / s
or q u s
In the case of a recessive lethal, s would be unity, so
-6-
 q 2 u and q u
In case of recessive homozygote if fitness value is 0.5 ( s = 0.5) and mutation rate , u , is 1 x 10-5 , then
the allelic frequency of selection mutation equilibrium will be
q u s 1 10 5 0.5 2 10 5 0.004
If the recessive phenotype were lethal then
q u s 1 10 5 1 0.003.
These are very low equilibrium values for the a allele.

Types of Selection Models : (One locus, twoallele selection Models, assuming all selection coefficients
are constants).
A1A1 A1A2 A2A2
1. Against recessive homozygotes. 1 1 1-s
2. Against heterozyotes. 1 1s 1
3. Against one allele( A2 only) 1 1 s1 1 s2
4. Against homozygotes. 1 s1 1 1 s2

Model 2 is interesting because selection against the heterozygote leads to an unstable equilibrium at
q=0.5. If one heterozygote is removed by selection, one each of the two alleles is eliminated. However, if
p and q are not equal (and thus not equal to 0.5) then one A1 allele is not the same proportion of the A1
alleles as one A2 allele is of all the A2 alleles. In other words, in a population of fifty individuals with
q=0.1 and p = 0.9, one A2 allele is 10% (1/10) of the A2 alleles, whereas one A1 alleles is only 1.1%
(1/90) of the A1 alleles Removing one each of the two alleles causes a decrease in q. Therefore, a
population, following model 2 is at equilibrium at p=q=0.5. However, this is an unstable equilibrium.
Any perturbation that changes the allelic frequencies causes the rare allele to be selected against and
eventually removed from the population. An example is the maternal-fetal incompatibility at the Rh
locus in human beings. The disease erythroblastosis occurs only in heterozygous fetuses ( Rh + / Rh ) in
Rh negative mothers, Heterozygotes are, therefore selected against.
In model 4 selection is against homozygous. This model is called the heterozygote advantage,
when heterozygote Aa has superior reproductive fitness to both homozygotes. In general, if the
heterozygote has an adaptive value of 1 while finesses of the homozygotes are reduced by the selective
coefficient s1 and s2, respectively. Thus, change in gene frequency of a in a single generation may be
calculated as follows :

AA Aa aa Total
Initial frequencies of diff. genotypes p2 2pq q2 1
Fitness (adaptive value) 1 s1 1 1 s2
Ratio after selection. P2(1s1) 2pq q2(1s2) 1s1p2 s2q2= W
Genotypic frequencies after Selection. p 2 1 s1 2 p2 q 2 1 s2
W W W

Frequency of recessive allele (a) after selection (q1) will be :

q 2 1 s 2 pq
q1
1 s1 p s 2 q
2 2
1 s1 p 2 s 2 q 2
q 2 s 2 q 2 pq

1 s1 p 2 s 2 q 2
pq q 2 s 2 q 2

1 s1 p 2 s 2 q 2

-7-
 q p q s 2 q

1 s1 p 2 s 2 q 2
q1 s 2 q

1 s1 p 2 s 2 q 2
The change in gene frequency in single generation ( q ) may be calculated as follows:
q1 s 2 q
q q
1 s1 p 2 s 2 q 2
q1 s 2 q q s1 p 2 q s 2 q 3

1 s1 p 2 s 2 q 2
q s 2 q 2 q s1 p 2 q s 2 q 3

1 s1 p 2 s 2 q 2
s1 p 2 q s 2 q 3 s 2 q 2

1 s1 p 2 s 2 q 2
s1 p 2 q s 2 q 2 1 p s 2 q 2

1 s1 p 2 s 2 q 2
s1 p 2 q s 2 q 2 s 2 q 2 p s 2 q 2

1 s1 p 2 s 2 q 2
s1 p 2 q s 2 q 2 p pqs1 p s 2 q

1 s1 p s 2 q
2 2
1 s1 p 2 s 2 q 2
When q is zero, equilibrium has been reached and there will be no further change in gene
frequency. Note that there are three possible conditions that will cause the numerator to be equal to zero,
either
P = 0, q = 0 or (s1p s2q ) = 0
If p = 0 or q =0 the results is trivial the equilibrium exists only because of the absence of one of the
alleles. The more meaningful equilibrium occurs when s1p s2q = 0
In that case
s1p = s2p or s1(1q) = s2q
s1
and q
s1 s 2
Since p+q=1
s2
p
s1 s 2
Several interesting conclusions follow :

First : Unlike the other models of selections this model allows a population to maintain both alleles. If s1
and s2 are constant values, both p and q will reach a stable equilibrium, i.e. if q departs from the
equilibrium value, selection pressure will force it back. This relationship arises from the change in q each
generation . If q is positive, the gene frequency q increase. If q is negative, q decrease. The negative or
positive sing of q depends on whether q is above or below its equilibrium value. On the other hand
when q is above the equilibrium value, q is negative and thus acts to decrease the value of q toward the
same equilibrium point. Both alleles therefore remain in the population at frequencies q^ and p^so long as
the selection coefficients confer superior fitness on the heterozygotes. The maintenance of different
genotypes in this fashion is an example of balanced polymorphism a term invented by Ford to
describe the preservation of genetic variability ( polymorphism) through selection.

Second : The equilibrium for each alleles frequency is independent of the original allelic frequencies
since it involves only the selection coefficients , s1 and s2.
-8-
Last, the equilibrium for each allele is directly proportional to the selection coefficient against the other
allele. As the selection against A increase (s1 increase), the equilibrium shift towards a higher value of q (
more a alleles).

MIGRATION & GENE FREQUENCIES :

Migration is similar to mutation in the sense that it adds or removed alleles and thereby changes
allelic frequencies. Human populations are frequently affected by migration.

Natural populations of virtually all species are usually subdivided into local subpopulations, each
of which tends to be randomly mating but to exchange genes occasionally as migrants move among local
units. If this gene flow is extensive, the whole population may be close to existing as a panmictic unit. If
little migration occurs, the sub population may be genetically quite different from one another because
they tend to diverge under the influence of random mutation and varied selection pressures in
heterogeneous environments. The amount of migration is therefore a determining factor in the level of
genetic differentiation among sub population of a species.

The new allelic frequencies in population (also called conglomerate allele frequency) that receives
migrant genes through interbreeding to produce the first generation are calculated with the formula.

p1 = p0 (1 m) + pm m .

Where p0 is the allele frequency in the recipient population, pm is the frequency of same allele for
the migrant, and m is the faction of migrant genes in the population, or the migration coefficient.

Suppose a population with the allele frequency p(A) = 0.9 and q (a) = 0.1 receive 10 percent
migrant genes whose allele frequencies are p(A) = 0.1 and q(a) = 0.9. The new allele frequencies in the
next generation will be

p1 = 0.9 x (1 0.1) + 0.1 x 0.1

= 0.82

and q1 = 0.18.

The frequency of A has decreased by nearly 10 percent, and the frequency of a has increased by
almost 100 percent from 0.1 to 0.18, in the recipient population in one generation. If the influx of
migrants continues, the allele frequency in the recipient population will be converted to the allele
frequencies in the population contributing the migrants. The speed and extent of change in allele
frequencies clearly vary with the original frequencies in the two population, the proportion of migrants,
the number of generation involved, and the degree of interbreeding between residents and migrants.

The change in allelic frequency for a from before to after the migration event may be calculated as :
q = q1 q0
= [ q0 ( 1 m ) + qmm] q0
= [ q0 q0m + qmm ] q0
= [ q0 + m ( qm q0 ) q0
= m ( qm q0)
At equilibrium condition, q^ (at q = 0) any multiplier with the value of zero makes the whole
expression zero, when either m = 0 or qm q0 = 0; qm = q0.
The conclusions we can draw from this model are intuitive. Migration can upset the Hardy
Weinberg equilibrium. Allelic frequencies in a population under the influence of migration will not
change if either the size of the migrant group drops to zero or the allelic frequencies in the migrant and
resident groups become identical.

-9-
 When a migrant group first joins a native group, before genetic mixing (mating) takes place, the
Hardy Weinberg equilibrium of the conglomerate population is perturbed, even though both subgroups
are themselves in Hardy Weinberg proportions. A decrease will occur in heterozygotes in the
conglomerate population as compared to what we would predict from the allelic frequencies of that
population (the weighted average of the frequencies of the starting population). This is a phenomenon of
subdivision referred to as the Wahlund effect. The reason this happens is because the relative
proportions of heterozygotes increase at intermediate allelic frequencies. As allelic frequencies rise above
or fall below 0.5, the relative proportion of heterozygotes decreases.

In a conglomerate population, the allelic frequencies will be intermediate between the values of the
two subgroups because of averaging. This generally means the predicted proportion of heterozygotes will
be higher than the actual average proportion of heterozygotes in the two subgroups. An example is
worked out in the table:

Subgroup 1 Subgroup 2 Conglomerate

p 0.1 0.9 0.5

q 0.9 0.11 0.5

Expected Observed

P2 0.01 0.81 0.25 0.41

2pq 0.18 0.18 0.50 0.18

q2 0.81 0.01 0.25 0.41

Table : The Wahlund effect : Heterozygotes frequencies are below expected in a conglomerate
population.

Assume that the two subgroups each make up 50% of the conglomerate population. In subgroup 1,
p =0.1 and q = 0.9 in subgroup2, p=0.9 and q=0.1. Each subgroup will have 18% heterozygotes. The
average, (0.18 + 0.18 )/2 =0.18 is the proportion of heterozygotes actually in the population. However,
the conglomerate allelic frequencies are p=0.5 and q = 0.5, leading to the expectation that 50% of the
population will be heterozygotes. Hence, the observed frequency of heterozygotes is lower the expected
frequency (i.e. the Wahlund effect).

SMALL POPULATION SIZE AND RANDOM GENETIC DIRFT

In addition to there directional forces (i.e. mutation, selection and migration) that change gene
frequencies progressively from one value to another, there are also changes that have no predictable
constancy from generation to generation. One of the most important of such nondirectional force arises
from variable sampling of the gene pool each generation and is known as random genetic drift.

The concept of random genetic drift (i.e. changes in gene frequencies due to chance alone) was
proposed by Sewall Wright in the early 1930s, also called Sewall Wright Effect. Genetic drift is caused
by the fact that real populations are limited in size rather than infinite, so that gene frequency changes
occur because of sampling errors. This is easy to see if we consider that when the number of parents of a
population is consistently large each generation, there is always a strong likelihood of obtaining a good
sample of the genes of the previous generation as long as directional forces are not acting to change them.

- 10 -
On the other hand, if only a few parents are chosen to begin a new generation, such a small sample of
genes may deviate widely from the gene frequency of the previous generation.

The extent of the deviation in both cases can be measured mathematically by the standard deviation of a
proportion pq N , Here p is the frequency of one allele, q of the other, and N the number of genes
sampled. For diploid parents, each carrying two genes,

pq 2 N e , where Ne is the number of actual parents or the effective population number (No.
of breeders).

For example, if we begin with a large diploid population, when p=q=0.5 and continue this
population each generation by using 5000 parents, then .5 .5 10,000 = .000025 =.005. The
values of such populations will therefore fluctuate mostly around 0.5 0.005 or between 0.495 and
0.505 .

On the other hand, a choice of only two parents as founders will produce a standard deviation of
.5 .5 4 .0625 .79, or between 0.29 to 1.29. In other words, sampling accidents because of
small population size may easily yield gene frequencies that are either 0 or 1. (since gene frequency
limits are also 0 or 1).

If such small sizes are continued each generation, the likelihood increases that such a population
will eventually reach fixation for an
allele. This changes in gene frequency
i.e. fixation or loss of an allele can
thus arise in the absence of any of the
directional force previously
considered. The attainment of
fixation, however dose not mean that
every small population will be fixed
for the same allele. If many such
small populations are considered
together, the average gene frequency
for all combined may remain fairly
constant, although the individual
populations involved have reached
fixation.

Wright has calculated the degree of fixation for different sized populations under a variety of
conditions. One set of relationships is shown in the following figure for different population sizes all with
an initial gene frequency of q = 0.5 when a small percentage of genes at this same frequency is
introduced by migration ( m = 0.0001)

When the population size is very large (N = 100,000) there is very little drift over a long period of
time and most frequencies cluster around the initial value q = 0.5 . As population sizes decrease, values
further from q = 0.5 are found, until when N = 1000, many population have reached fixation for one of
the two alleles.

The tendency towards fixation of an allele by random drift may of course be counteracted by
selective force acting to eliminate it. However, for alleles that are neutral in their effect, the chances of
fixation seen to depend mostly on their mutation rate. This has been pointed out by Kimura and
coworkers who reason that a population of N individuals bearing 2N genes will have 2N newly arisen
mutations if the chance for each gene to mutate is . If all or most of these mutant genes are of equal
neutral effect, each will be present in about N frequency and will probably persist in this frequency
- 11 -
because one is no better than the other. Thus there are a total of 2N neutral mutations, each with a N
chance of fixation (and a 1 N chance of elimination) or the chance of fixation for a particular neutral
gene is 2N X N = .

That is, the chances for fixation of neutral alleles in population appears to be independent of
population size. Kimura therefore suggests that if their collective mutation rate is substantial, neutral
alleles may be widely prevalent in all populations and account for the large amount of genetic variability
that is often present.

However, on an individual basis the time necessary to attain fixation for any particular size, since
the random drift process in small populations greatly speeds up the fixation of these genes although it
does not change their probability of fixation. Kimura and other have calculated that the average number
of generations necessary for the fixation of new neutral mutation is approximately four times the number
of parents in each generation. Thus, a population experiences the effect of random genetic drift in inverse
proportion to its size small populations rapidly fix or lose a give allele, whereas large populations take
longer to show the same effects.

Founder Effects and Bottlenecks :

Several well known genetic phenomena are caused by populations starting at or proceeding through
small numbers. When a population is initialed by a small, and therefore genetically unrepresentative,
sample of the parent population, the genetic drift observed in the subpopulation is referred to as a founder
effect. A classical human example is the population founded on Pitcairn Island by several of the Bounty
mutineers and some Polynesians. The unique combination of Caucasian and Polynesian traits that
characterize todays Pitcairn Island population resulted from the small number of founders for the
population.

Sometimes populations go through bottlenecks periods of very small population size, with
predictable genetic results. After the bottlenecks, the parents of the next generation have been reduce to a
small number and may not be genetically representative of the original population. Such population
bottlenecks may have a long lasting effect and cause a significant reduction in genetic variability many
generations after Ne has been increased to a substantial number. An example of a severe bottlenecks
effect is provided by the northern elephant seal (Mirounga angustirostris). As a results of unrestrained
hunting, only about 20 animals remained by the turn of 20th century. After passage of protective
legislation in 1992 and later, the seal population off the coast of Mexico and California grew and is now
over 100,000. From a study made in 1974, it is clear that the present norther seal population has a low
level of genetic variability. These genes are polymorphic in other animal species including the souther
elephant seal, which did not experiences a bottleneck.

Another example of startlingly low genetic variability is the cheetah (Ainonyx jubatus), a member
of the cat family. The species once was worldwide and numerous, but only about 20,000 cheetahs are
believed to remain today, and they are restricted to a few pockets in Africa. The steady decline in the
number of cheetahs led to attempts to breed the animals in captivity but with very little success.
The peril of bottlenecks is based on the relatively high genetic load in diploid populations.
Deleterious recessive alleles are fixed by chance alone in very small populations and matings take place
between close relatives, especially if the population expands slowly. Inbreeding leads to reduced
heterozygosity, causing lower vigor and fertility as harmful recessive traits are expressed and no longer
masked in heterozygotes. The great concern about endangered species is due as much to this problem as
to numerical depletion of breeding individuals to zero and consequent extinction a species. Once a locus
has become homozygous in a population, the only means to restore a lost allele and increase variation is
by mutation or by gene flow from other populations. Inbreeding of captive animals from different
subpopulations of an endangered species can increase variation rapidly, if different loci are homozygous
as well as if more of the genes are heterozygous in the subpopulation.

- 12 -