What you are expected to know by now

MENDELIAN GENETICS
Basic Genetic Terminologies
Genotype, Phenotype
Dominance, Recessive
Genes, Alleles, Loci
Homozygous, Heterozygous, Diploid, etc
Mendelian Laws
Law of Segregation – Monohybrid Crosses, Punnett Square
Law of Independent Assortment – Dihybrid Crosses, Trihybrid Crosses,
Partial Dominance, Backcross, Testcross
Sex Chromosome
Sex Determination – Factorial calculations
Sex Linkage – Reciprocal Crosses
Sex Linkage in Humans
Influence of Barr Bodies
Sex-influenced Traits, Sex-Limited Traits

MODES OF INHERITANCE
PEDIGREE ANALYSIS

PENETRANCE AND EXPRESSIVITY

PLEIOTROPY
 What you are expected to know by now
VARIATIONS TO MENDELIAN GENETICS

(including Sex linkage)

Multiple alleles
- examples in Drosophila
- examples in Human (blood groupings), Bombay phenotype

Gene-gene Interaction (Epistasis)

Lethal genes/alleles

Non-disjunction

Examples of other Non-Mendelian modes of inheritance

Linkage, Crossing over, Linkage disequilibrium and Mapping

POPULATION GENETICS
 What you will cover in this lecture
POPULATIONS IN EQUILIBRIUM
Hardy-Weinberg Equilibrium
Single gene locus (autosomal, additive gene action) (e.g. MN blood group)
Gene frequencies
Single gene locus, 2 alleles (autosomal, codominance)
Single gene locus, 2 alleles (autosomal, complete dom.)
Single gene locus, multiple alleles (autosomal)
Single gene locus, sex-linked

NON RANDOM MATING

POPULATION GENETIC FORCES THAT CHANGE ALLELE FRQUENCIES

Mutation
One-way recurrent mutation
Two-way recurrent mutation
Selection
Selection against recessive gene
Selection favouring heterozygotes (overdominance)
Migration (not covered, but do you know how to apply the same principles!!!)
Genetic Polymorphism
 RECOMMENDED TEXT

D. S. Falconer & T.F.C. Mackay.

(1996)
Introduction to Quantitative Genetics

4th Edition, Longman

Hardy-Weinberg Equilibrium
 Population Genetics

Deals with
• Frequencies/distribution of genes
(alleles), genotypes, and phenotypes in
populations.

• Factors that maintain equilibrium or

change gene, genotype and phenotype
frequencies over time.
 A Genetic Population

Definition:
• Large group of inter-breeding
individuals which shares a common
gene pool.

• A group of sexually reproducing

organisms.
 The Hardy-Weinberg Principle

• Proposed independently in 1908 by

English mathematician G.H. Hardy and
German physician W. Weinberg.

• Relates allele/genotype frequencies at a

single Mendelian locus to phenotype
frequencies in a population.
 The H-W Principle
• Relative frequency (proportion) of genes
(alleles), genotypes and phenotypes remains
unchanged in the 2nd generation.

• No matter how many generations are studied,

the relative frequencies will remain constant.

• Actual numbers of individuals with each

genotype (phenotype) will change as
population size changes, but relative
frequencies will remain constant.
 H-W Equilibrium
• If a gene has 2 alleles, D and d, with
population frequencies of p and q,
respectively.
p+q = 1
• With 2 different alleles, there are 3 possible
genotypes: DD, Dd, & dd.
• Given allele frequencies of p and q, when a
population is in Hardy-Weinberg equilibrium,
these genotypes will have frequencies of p2,
2pq, and q2, respectively.
p2 + 2pq + q2 = 1
(A binomial distribution)
 H-W Equilibrium

• E.g. for a gene with 2 Male Gametes

alleles D and d, with D d
population frequencies of p
and q respectively. (p) (q)

Female Gametes
• Genotype/phenotype D DD Dd
frequencies after 1
generation: (p) (p2) (pq)
DD (D homozygotes) = p2
d Dd dd
Dd (Dd heterozygotes) = 2pq
dd (d homozygotes) = q2 (q) (pq) (q2)

Punnett Square
 H-W Equilibrium

Genotype (and frequency) of male parent

DD Dd dd
Genotype (and frequency)

(p2) (2pq) (q2)

of female parent

DD p4 2p3q p 2q 2
(p2)
Dd 2p3q 4p2q2 2pq3
(2pq)
dd p2q2 2pq3 q4
(q2)
 H-W Equilibrium
Frequency of Offspring
Mating type Mating DD Dd dd
Frequency

DD x DD p4 p4 -- --
DD x Dd 4p3q 2p3q 2p3q --
Dd x Dd 4p2q2 p2q2 2p2q2 p2q2
DD x dd 2p2q2 -- 2p2q2 --
Dd x dd 4pq3 -- 2pq3 2pq3
dd x dd q4 -- -- q4
Total p2(p2+2pq+q2) 2pq(p2+2pq+q2) q2(p2+2pq+q2)
Relative freq p2 2pq q2

Allele and genotype frequencies remain the same after each successive generation
 H-W Equilibrium
1.0

A1 A1 A2 A2

A1 A1
(p2) A2 A1

Male gametes
A1 A2 (qp)

0.5

A1 A2 A2 A2
(pq) (q2)

Female gametes
0.0 0.5 1.0
Allele Freq of A2 (q)
 Assumptions of H-W Principle
• Large population size – small populations are more
susceptible to random fluctuations of allele
frequencies (due to transmission of any one allele by
chance), a phenomenon called genetic drift.

• Random mating – population stratification (e.g. based

on ethnicity or religion), assortative mating (choice of
mates based on desired traits), or inbreeding are
different forms of non-random mating, which can lead
to an  in the frequency of homozygotes in the sub-
population or pedigree.

• No migration – movement of individuals between

populations can gradually  or  gene frequencies, or
introduce new alleles – gene flow.
 Assumptions of H-W Principle
• No new mutation – new mutations constantly
occur and will  gene frequency, but these are
offset by those lost by death. However,
changes in mutation rates can  or  gene
frequency.

• No selection – selection against a mutant

allele will  gene frequency, but this is offset
by new mutations. However, increased
reproductive fitness will  gene frequency.
Selection for a mutant allele, e.g. heterozygote
advantage of sickle-cell trait, will  the
proportion of the advantaged genotype.
 H-W Principle
• H-W equilibrium is attained after 1 generation if all
assumptions hold true.
• This equilibrium will be maintained from
generation to generation as long as conditions do
not change.
• Question: The above applies to autosomal genes only
(and also only in diploidic populations).
Find out the behaviour of sex-linked (or X-linked) genes.

• In reality, no population satisfies the Hardy-Weinberg equilibrium completely.

• However, in some large natural populations there is little migration and negligible natural selection
– In these cases, the HW equilibrium is nearly approximated for certain genes.
For sex-linked loci, if allele frequencies in males and females are initially
unequal, the frequency in males in generation n will be equal to that in
females in the preceding generation n-1. The male f(a) therefore "chases"
the female f(a) until they reach an equilibrium.
 H-W Principle

(Micro) Evolutionary Forces:

Five major forces can cause evolutionary change: IMPORTANT!!!

Natural selection

Genetic drift (or population size)

Mutation

Non-random mating

Migration (in the genetic sense of permanent movement

of genes/alleles from one location to another)
Stability of Genes Frequencies

A freq (p) = 0.5, a freq (q) = 0.5

Computer simulated
graph showing stable
gene frequencies in a
large randomly
mating population in
H-W equilibrium.

Audesirk, Fig 15-2. pg 291

Example of Past Continual Assessment
In 1979, Rich et al. (Evolution, 33: 579-84) published the results of a
study on changes in allele frequencies in populations of the flour
beetle, Tribolium castaneum. The began their experiments with two
true-breeding populations: one that was homozygous for a mutant
allele called b, and another that was homozygous for the wild-type
allele b+.
Beetles that are homozygous b+b+ have red body colour, while
those that are homozygous bb have black body colour.
Heterozygous b+b have brown body colour. Thus the researcher
could easily distinguish all three genotypes on the basis of their
phenotypes and thereby determine the allele frequencies of b+ and b
in the population.
The researcher hybridized individuals from the two true-breed
populations to produce F1 offsprings that were all heterozygous b+b.
They then sub-divided the heterozygous F1 individuals into 48
populations:
12 populations maintained at 10 breeding individuals per generation
12 populations maintained at 20 breeding individuals per generation
12 populations maintained at 50 breeding individuals per generation
12 populations maintained at 100 breeding individuals per generation
Equal numbers of males and females were selected at random as
breeding individuals for each generation in each population. The
results over 20 generations are shown in the figure.
Describe (in your own words) the evidence of random genetic drift
and selection from the results of this study.
 Answer
(30 marks in total)
• Random variations in allele frequencies among populations are
evidence of genetic drift occurring. (5 marks)

• The magnitude of drift is indicated by the degree of random variation

within each set of populations. (5 marks)

• Genetic drift is greatest in the set of populations with 10 breeding

individuals, (2.5 marks)

• and least in the set of populations with 100 breeding individuals. (2.5
marks)

• The magnitude of genetic drift is inversely proportional to breeding

population size. (5 marks)

• Observation: The average frequency of the b+ allele increased in all

four sets of populations. (5 marks)

• Explanation: The average increase in the frequency of the b+ allele is a

consequence of natural directional selection that favours the b+ allele in
such breeding environment. (5 marks)
 CALCULATION OF GENE FREQUENCIES

Genotype A1A1 A1A2 A2A2 Total

Genotype freq. P H Q 1
(Probability)

Frequency of A1 allele : p = (P + ½H)/Total

p = P + ½H

Frequency of A2 allele : q = (Q + ½H)/Total

q = Q + ½H
 EXAMPLE: H-W EQUILIBRIUM

• The M-N blood group in man is determined by 2

alleles at a single autosomal locus.

• Test whether this population is in H-W

equilibrium.

Genotype MM MN NN TOTAL

Obs. Frequency P H Q 1

Obs. number 50 86 45 181

CALCULATION OF M & N ALLELE FREQUENCIES

Calculate the values of p and q

frequency of M
p = (P + ½H)/Total allele

= (50 + 86/2) = (50 + 43) = 93 = 0.51

181 181 181

q = (Q + ½H)/Total
= (45+ 86/2) = (45+43) = 88 = 0.49
181 181 181
CALCULATIONS OF ALLELE FREQ. OF M & N

Use the χ2 test to test hypotheses

Ho : Population is in H-W equilibrium.
H1 : Population is not in H-W equilibrium.

Genotype MM MN NN TOTAL
Exp. freq. p2 2pq q2 1
Exp. No. (p2181) (2pq181) (q2181) 181
= 47.1 = 90.5 = 43.4 181

Where p = 0.51
q = 0.49
 CALCULATIONS OF χ2
EXPECTED FREQUENCIES OF THE 3 GENOTYPES

Exp. freq. of MM genotype = p2 = 0.512 = 0.2601

Exp. freq. of MN genotype = 2pq = 2 x 0.51 x 0.49 = 0.4998

Exp. freq. of NN genotype = q2 = 0.4902 = 0.2401

EXPECTED NUMBERS OF THE 3 GENOTYPES

Exp. number of MM = p2 x 181 = 0.2601 x 181 = 47.1

Exp. number of MN = 2pq x 181 = 0.4998 x 181 = 90.5

Exp. number of NN = q2 x 181 = 0.2401 x 181 = 43.4

 CALCULATIONS OF χ2

χ2 = Σ (Obs. No. – Exp. No.)2

Exp. No.

= (50 – 47.1)2 + (86 – 90.5)2 + (45 – 43.4)2

47.1 90.5 43.4
= 2.92 + -4.52 + 1.62
47.1 90.5 43.4

= 8.41 + 20.25 + 2.56

47.1 90.5 43.4

= 0.179 + 0.224 + 0.059

= 0.462
Compare calculated χ2 with theoretical χ2
 CALCULATIONS OF χ2

• Check critical χ2 value from the table

• Theoretical χ2 = χ2α[υ] = χ20.05(3-2) = 3.841

• Since the calculated χ 2 (0.462) < theoretical χ2

• Conclusion: This population did not deviate

significantly from expected H-W genotype proportions
for the MN locus
 GENE FREQUENCIES - SUMMARY

(A1 gene) p from 0 1

(A2 gene) q from 0 1

p+q = 1
• Gene frequencies around 1 or 0 are considered extreme

• Gene frequencies around 0.5 considered intermediate

• At intermediate gene frequencies, heterozygotes in a

population would be near the max. frequency of 0.5 (50%)
 SINGLE GENE LOCUS
AUTOSOMAL TWO ALLELES, CODOMINANT
GENES (ALLELES) A1 A2

GENE FREQUENCY p q

GENOTYPES A 1A 1 A 1A 2 A 2A 2 TOTAL

Exp. genotype freq. p2 2pq q2 1

Obs. genotype freq. P H Q

Able to distinguish the 3 genotypes

p = P + ½H q = Q + ½H
TOTAL TOTAL p+q=1

EXAMPLE: M-N BLOOD GROUP IN HUMANS

GENOTYPES MM MN NN
 SINGLE GENE LOCUS, AUTOSOMAL TWO
ALLELES, COMPLETE DOMINANCE

EXAMPLE : ALBINISM IN MAN

SINGLE AUTOSOMAL LOCUS, complete dominance

TWO ALLELES : A – normal pigmentation (dominant)

a – albinism (recessive)

• In populations, heterozygotes cannot be

distinguished from dominant homozygotes (AA).

• In a certain pop., the freq. of albinos (aa) is about

1/20,000.

• What is the freq. of heterozygous carriers?

 SINGLE GENE LOCUS, AUTOSOMAL TWO
ALLELES, COMPLETE DOMINANCE

Phenotypes Normal Albino Total

Genotypes AA Aa aa

Exp. freq. p2 2pq q2 1

Obs. freq. ? ? 1/20,000 1

• Assume Exp. freq. = Obs. freq.

• Therefore q2 = 1/20,000 , q = 1/141

• Freq. of carrier (Aa) = 2pq = 2  1/141  140/141

= 1/70

About one in 70 persons is a carrier.

 MULTIPLE ALLELES
SINGLE LOCUS AUTOSOMAL
• 1 single locus with than 2 alleles
• Genotype frequencies can be found by
expanding equations
• 2 Alleles with frequencies p & q
– Expand : (p + q)2 (binomial equation)
• 3 Alleles with frequencies p1 q1 & r
– Expand : (p + q + r)2
• n Alleles with freq p1, p2, p3, ….. Pn
– Expand (p1 + p2 + p3 + … + pn)2
 MULTIPLE ALLELES: HUMAN A-B-O BLOOD GROUPS

EXAMPLE: A-B-0 HUMAN BLOOD GROUP

• Single autosomal locus
• 3 Alleles : IA (p) codominant
IB (q)
I0 (r ) - recessive
• Possible genotypes
IAIA, IAIO, IBIB, IBIO, IAIB, IOIO
• Exp. genotype frequencies found by expanding
(p + q + r)2
• Phenotypes : A blood group
B blood group
AB blood group
O blood group
MULTIPLE ALLELES: HUMAN A-B-O BLOOD GROUPS

• In a Scottish population, the observed

numbers of individuals in the A,B, AB and O
blood groups are given.
• What are the gene frequencies in this pop?
(evaluate p, q and r)
 HUMAN A-B-O BLOOD GROUPS
GENOTYPIC AND PHENOTYPIC FREQUENCIES

Data of ABO Blood Types in Scottish Population

Phenotype A B AB O Total
Genotype IAIA IAIO IBIB IAIO IAIB IOIO 1
Exp. genotype
Frequencies p2 2pr q2 2qr 2pq r2 1
Observed No. 894 309 70 1337 2610
Of Phenotypes

Observed freq. Of 894/2610 309/2610 70/2610 1337/2610 1

Phenotypes = 0.342 = 0.119 = 0.027 = 0.512
 HUMAN A-B-O BLOOD GROUPS
CALCULATION OF GENE FREQUENCIES (p, q & r)

• Assume that the pop. is in H-W equilibrium.

first statement is important!! cannot
calculate without assumption
• Freq. of Io gene is r

• Given that r2 = 0.512, therefore r = 0.715

• Freq of IA (p) and IB (q) genes can be found indirectly

• Freq. of A and O phenotypes = p2 + 2pr + r2

• = (p + r)2
substitute
• since p + q + r = 1, therefore (p + r) = (1 – q)
 HUMAN A-B-O BLOOD GROUPS
CALCULATION OF GENE FREQUENCIES (p, q & r)

Freq. of A & O phenotypes = (1 – q)2

0.342 + 0.512 = (1 – q)2

1 – q = 0.854

q = 0.076 (frequency of the IB allele)

p=1–q–r

= 1 – 0.076 – 0.715

= 0.209 (frequency of IA allele)

http://www.umds.ac.uk/physiology/daveb/brainday/colourblindness/cblind.htm

Color blindness afflicts 8% of males and 0.04 % of human females.

Color perception depends on three genes, each producing chemicals sensitive

to different parts of the visible light spectrum.

Red and green detecting genes are on the X-chromosome, while the blue
detection is on an autosome.
 SINGLE GENE LOCUS, SEX-LINKED
TWO ALLELES

In Humans ♀ is XX (homogametic)
♂ is XY (heterogametic)
Single locus (sex-linked)
2 alleles : A1 A2
Frequency : p q

FEMALE MALE
GENOTYPE A1 A1 A1 A2 A2 A2 A1Y A2Y

OBS. NO. P H Q R S
 SINGLE GENE LOCUS, SEX-LINKED
TWO ALLELES
Freq. of A1 among ♀♀ : pf = (P + ½H)
Total ♀♀
Freq. of A1 among ♂♂ : pm = R
Total ♂♂
(assuming equal ♂♀ population)

Freq. of A1 in whole population

3 X chromosomes in
p = 2/3 pf + 1/3 pm total, 1 from male and
2 from female

Freq. of A2 in whole population

q = 2/3 qf + 1/3 qm
Population at equilibrium: pf = pm and qf = qm
HW equilibrium
 SINGLE GENE LOCUS, SEX-LINKED
EXAMPLE FROM HUMANS (COLOR BLINDNESS)

• Color blindness in man is due to a recessive

sex-linked gene (c)
• Freq. of colorblind men is 7.8%
• Freq. of colorblind women is 0.65%
• What is the freq. of heterozygous women in this
pop.?
♀♀ ♂♂
Genotype CC Cc cc C c
Obs. freq. ? 0.0065 0.078
Exp. freq. p f2 2pfqf qf 2 pm qm
 SINGLE GENE LOCUS, SEX-LINKED
EXAMPLE FROM HUMANS (COLOR BLINDNESS)

p = freq. of normal gene, q = freq. of c.b. gene

Among females : q2f = 0.0065 therefore qf = 0.0065

= 0.081
Among males : qm = 0.078 (given)
overall pop.
freq.
Overall in pop: q = 2/3 qf + 1/3 qm
= (2/3  0.081) + (1/3  0.076) = 0.08
Therefore p = 1 – q = 1- 0.08 = 0.92

Freq. of heterozygotes ♀♀ = 2 p q
= 2  0.92  0.08
= 0.147 ≈ 15%
 To calculate if the allele frequency of one
population differs from another population:
Population I Population II
Allele frequency p1 p2
Population size n1 n2

p1 - p2
z score = p1(1-p1) + p2(1-p2) z score calculates
proportions, chi test
calculates whole
 n1 x 2 n2 x 2 numbers

z score is significantly different if >1.96

p 0.2 0.1 0.05 0.01 0.001

z 1.28 1.65 1.96 2.58 3.29

 ACTUAL PUBLISHED EXAMPLE
Allergy 1999; 54: 1005-7.

Evaluate differences in
Determine HWE genotype frequencies
Mutation & Selection
 Terminology

Mutation
• A change in the genetic material, either of a single
gene or in the number of structure of the
chromosomes.
• A mutation which occurs in the gametes is inherited
but not otherwise (ie, those in somatic cells)

Polymorphism
• The occurrence in a population of two of more
genetically determined forms in such frequencies
(>1%) that the rarest of them could not be maintained
by mutation alone.
 Terminology
• Changes in gene frequencies when small
groups of individuals are separated from
or leave a larger populations.

• Founder effect – A type of genetic drift in

human populations in which a few
members leave to found a new settlement,
perpetuating a subset of the alleles in the
original population.
Genetic drift is a mechanism of evolution in which allele
frequencies of a population change over generations due to
• Define: Genetic drift chance (sampling error).

When a population goes through a catastrophic

• Define: Bottleneck event (eg mass hunting, fire) that suddenly and
significantly reduces its population size.
A comparison of polymorphisms in different species

Genetic
variation near
zero

While ~ 30% of all genes

are polymorphic in
human populations

Less than 10% of

all genes are
heterozygous
within any given
individual
 NON-RANDOM MATING
I. ASSORTATIVE MATING (selective mating)
Leads to increase in frequencies of homozygotes
and decrease in heterozygotes. The pop. becomes
partially divided into 2 groups, mating takes place
more frequently within groups. Most extreme form is
inbreeding

II. DISSORTATIVE MATING (best case scenario is random mating)

Leads to an increase of heterozygotes and a reduction
of homozygotes.

Mating and genotypes

Inbreeding is the mating between genetically-related individuals
Outbreeding is the mating between genetically-unrelated individuals

Note: In the absence of other evolutionary forces, allele frequencies are not affected by
in- or out-breeding. However, these patterns of mating do disrupt the balance of
genotypes that is predicted by the HW equilibrium.
 INBREEDING

Said to be
inbred

A human pedigree containing inbreeding

 INBREEDING

• Inbreeding can have both positive and negative

consequences in a population

• The positive side is seen in the field of agriculture

– Inbreeding results in a higher proportion of homozygotes,
which may exhibit a desirable trait

• On the negative side, many genetic diseases are

inherited in a recessive manner
– Inbreeding increases the likelihood that an individual will
be homozygous and therefore afflicted with the disease
homozygous recessive
disease
FORCES THAT CHANGE GENE FREQUENCIES

- Systematic processes
1. MUTATION - amount and direction

2. SELECTION of change are predictable

 TYPES OF MUTATION
Changes in genes. Source of new genetic variation
Mutation rate is low  10-5 or 10-6

1. NON-RECURRENT MUTATION
– Rare event
– Not important
A1 A2
2. RECURRENT MUTATION
– Mutational event at a specific gene locus. It
occurs with a characteristic frequency.


A1 A2
 = mutation rate of gene A1 to A2
 RECURRENT MUTATION

2 Types
1. One-way recurrent mutation
A1  A2
(Initial gene freq.) po qo

Results in: Decrease in freq. of A1 gene (p 0)

Increase in freq. of A2 gene (q 1)
Δp = change in freq. of A1 gene due to 1
generation of one-way recurrent mutation.
 RECURRENT MUTATION
One-way recurrent mutation
Δp = mut. rate  orig. freq. of A1
Δp = po
p1 : freq. of A1 gene after 1 generation of one-way recurrent
mut.
p1 = po - po
p1 = po (1 – )
p2, the freq. of A1 will decrease by the amount p1
p2 = p1 – p1
p2 = p1 (1 – )
p2 = po (1 – ) (1 – )
p2 = po (1 – )2

Repeating the process for t generations

pt = po (1 – )t
 RECURRENT MUTATION
2. Two-way recurrent mutation

Change of frequencies of the A1 and A2 alleles


A1 A2

po qo

Forward mut: Freq. of A1 will decrease by - po

Backward mut: Freq. of A1 will increase by +vqo

Net change in A1 after 1 gen. of 2-way recurrent

mut.
Δp = qo - po
 RECURRENT MUTATION
Two-way Recurrent Mutation
Gene Frequencies At Equilibrium
AT EQUILIBRIUM
- no net change in gene frequencies
- pe, qe are equilibrium gene frequencies
- qe = pe therefore Δp = 0
Δp = qe - pe
qe - pe = 0 Let pe = (1-qe)
qe -  (1 – qe) = 0
qe -  + qe = 0
 qe + qe = u Similarly
qe =  pe = 
+ +
 EFFECTS OF MUTATION ON GENE FREQ.
1. One-way Recurrent Mutation
• Mutation rates are generally very low
• 10-5 or 10-6/ generation
• Freq. of the mutant gene slowly increases
• May be important on an evolutionary time scale
• Loss in genetic variation

2. Two-way Recurrent Mutation

• A state of equilibrium is reached.
• Equilibrium point dependent on the relative rates of
the forward and backward mutation rates
pe =  qe = 
+ +
•  is about 1/10th as frequent as 
• Genetic variation is maintained
 SELECTION
• Individuals differ in viability and fertility
• They therefore contribute different numbers of
offspring to the next generation
• FITNESS (adaptive value or selective value) is
the contribution of offspring to the next
fitness is the ability of an organism to survive to
generation reproductive age, as well as its ability to reproduce.
• Natural or artificial selection operates on the
gene
• Therefore causing changes in the gene
frequency
 FITNESS
• In a particular environment, the most favored
genotype (fittest) has optimum fitness of 1
• Contributes the most offspring to the next
generation.
• The fitness (W) of the genotypes selected against
is 1- s
• s is the coefficient of selection
• This is the proportionate reduction in the gametic
contribution of particular genotype
• s is also referred to as the selection intensity
 FITNESS
• If s = 0:
Fitness = (1- s) = 1 (no selection against genotype)

• If s = 1:
Fitness = 0 (complete selection against genotype)

• If s = 0.1: Fitness = 0.9

• For every 10 zygotes produced. By the fittest
genotype, the genotype with fitness of 0.9
produced only 9.
• Examine the degrees of dominance in relation to
fitness.
Degrees of Dominance in Relation to Fitness

(Falconer, Fig 2.1)

SELECTION AGAINST A RECESIVE GENE

A Hopi Albino girl.

Weaver & Hedrick, Fig 2.17, pg 36
 SELECTION AGAINST A RECESIVE GENE

EXAMPLE – ALBINISM (A > a)

Complete selection against the recessive albino gene, a.
s = 1 (fitness = 0) if albino are prevented from reproducing
Present frequency of albinos = 1/20,000 in Europe
After 100 gen. of selection against albinos (t = 100), what is
the frequencies of albinos in this population?

Phenotype Normal Albino

Genotype AA Aa aa TOTAL
Exp. Freq. p2 2pq q2 1
Fitness 1 1 1-s
Gametic contrib. p2 2pq q2(1-s) 1-sq2
NO. OF GENERATIONS REQUIRED TO PRODUCE A CHANGE OF
FREQUENCY OF A RECESSIVE GENE (t)

Initial frequency of a (albino gene) = q

Freq. after 1 generation of selection = q1
q1 = q2(1-s) + pq since (1-s) = 0, s=1, and p=1-q
1-sq2
q1 = q (1-q)
1 – q2 (substitute 1 – q2 = (1-q)(1+q)
q1 = q
1+q
After 2 generations of selection : q2
q2 = q 1 (substitute q1 = q/ 1+q1 )
(1+ q1)
q2 = q
1 + 2q
 NO. OF GENERATIONS REQUIRED TO PRODUCE A CHANGE
OF FREQUENCY OF A RECESSIVE GENE (t)

After t generations : qt = q
1 + tq
After 100 generations of selection ( t = 100) assuming at the start, it's
in HW equilibrium
Gen. 0: q =  1/20,000 = 1/141 p = 140/141
Gen. t = 100 q100 = q
1+ tq
q100 = 1/141 / 1 + (100  1/141)
q100 = 1/241
Therefore freq. of albinos (aa) after 100 gens.
q2100 = (1/241)2 = 1/58,080
One person in 58,080 persons is expected to be an albino.
 Overdominance
Selection favouring heterozygotes
Genotype A 1 A1 A1A2 A2A2 Total
Exp. freq p2 2pq q2 1
Rel. fitness 1-s1 1 1-s2
Gametic p2(1-s1) 2pq q2(1-s2) 1-s1p2-s2q2
contribution

Frequency of the A2 allele after 1 generation of selection:

q1 = No. of A2 genes
New total
q1 = q2(1-s2) + pq
1 – s1p2 – s2q2
 Overdominance
Change in gene frequency due to one generation
of selection:
 q = q1 – q dont need to know
how to derive
 q = pq (s1p – s2q)
1 – s1p2 – s2q2
At equilibrium - q=0
then s1p = s2q
Therefore at equilibrium s1pe = s2qe
Additional slide for those who have always asked to see the actual workings to
derive the formula:
(Skip this slide if you are not interested)

Since delta q = q1-q and q1 is given in the previous slide, I tried to solve q1-q by:

To keep it simple, I am just solving the numerator,

q2 (1-s2) + pq -q(1-s1p2-s2q2)
=q2-s2q2 + pq - q + s1p2q - s2q3
=q ( q-s2q + p -1 + s1p2 +s2q2)

Try and make p common for all terms within the bracket by substituting q = 1-p,
for the last term, I substituted q = 1-p for one of the q in q2

=q (1-p-s2q + p -1 +s1p2 + s2q -s2qp)

Some of the terms like 1, p and s2q cancel out one another, leaving

= q (s1p2-s2qp)

Take out p
= pq (s1p-s2q) Hoola! which is the same as the numerator in the delta q.
 Overdominance
Gene frequencies at equilibrium:
frequency of
s1pe = s2qe expression of s1pe = s2qe
A/a at
s1pe = s2 (1- pe) equilibrium s1(1-qe) = s2qe
pe = s2 qe = s1
s 1 + s2 s 1 + s2
• Equilibrium gene frequencies are dependent on the
relative fitness of the two homozygote (s1 and s2)
• The 3 genotypes are always present in the pop at fairly
like mutation equation! not
high frequencies. dependent on original allele
frequency (p/q0)
this is the pattern of all selection
pressures.
 Overdominance Summary
GENETIC POLYMORPHISM
• More than one genetic form is maintained; A1A1, A1A2, and
A 2A 2 .
• Genetic variability is maintained.
• AT EQUILIBRIUM, GENE FREQUENCES ARE MAINTAINED AT
INTERMEDIATE LEVELS. intermediate: 0.05 - 0.95
• Arbitrary range 0.01 to 0.99
• The commonest allele is not > 0.99.
• The rarest allele is not < 0.01
• Equilibrium gene frequencies (pe, qe) must be too high to be
maintained by balance between mutation and selection.

Schools of thought
SELECTIONISTS:
POLYMORPHISMS ARE BALANCED (SELECTIVE FORCES)

NEUTRALISTS :
POLYMORPHISMS HAVE NO SIGNIFICANCE (mutation & finite pop. size) e.g., Kimura
 Overdominance Example

Example: Sickle-cell anaemia

Normal red blood cells Sickle-shaped red blood cells

(Lewis, pg 183)
 Sickle-cell anaemia
• Such cells occur in people carrying a mutant gene,
which causes crystalloid aggregates resulting in
functional abnormality along with distorted
morphology.

• The sickle-shaped cells clog small blood vessels,

interfere with oxygen transport to various tissues,
and cause anemia.
the disease itself is a selection pressure against
homozygous recessive phenotypes (likely to die before
reaching reproductive age)
Sickle-cell anaemia: Distribution of Malaria correlates with the
distribution of sickle cell gene (Hbs)
sickle cell allele is found where
malaria is endemic.
heterozygous phenotype is
selectively advantaged (greatest
fitness) as it is resistant to malaria
and hence is more likely to live to
reproductive age (recessive allele
continues in the population, in a
state of overdominance).
Distribution
of Malaria

Distribution of
sickle cell
gene (Hbs)
Starr & Taggart Pg.291,
Fig.18.11
 Sickle-cell anaemia in Humans: Example

Hbs gene is present among Africans and their

descendants in America.

Sickle-cell Sickle-cell
Phenotype Normal trait anaemia
Genotype HbAHbA HbAHbs HbsHbs
Initial freq p2 2pq q2
Fitness 1-s1 1 1-s2

heterozygotes are still susceptible,

but as long as they are the fittest,
fitness = 1 (relative fitness)
if they are shifted to America (eg), malaria is not
endemic -> s1 = 0
s2 will still be high and hence diseased
phenotype will have low frequency.
 Sickle-cell anaemia in Humans: Example

• In West Africa, the equilibrium freq of the Hbs gene,

qe = 0.1 (rather high freq)
• Frequency the HbA gene (normal gene), pe = 0.9
• Assume HbsHbs homozygotes do not leave offspring,
i.e. s2 = 1 and fitness = 0
• What is the fitness of normal homozygotes
compared with heterozygotes? (evaluate 1-s1)
qe = s1 qe = 0.1
s1 + s2 s2 = 1
s1 = 1/9
Therefore - fitness of HbAHbA (W) = 1-s1 = 1-1/9 =
8/9
 Possible example of overdominance
ABO blood group in humans

A possible example of heterozygote

advantage in AB0 human blood groups.

Why are 3 alleles (IA, IB and Io) maintained at

intermediate levels in human populations?

There may be a correlation with resistance to

certain human diseases
Overdominance - Possible correlation between
incidence of ABO genes with diseases

Relative Incidence of Diseases in Relation to ABO

Blood Types

1.5

1 O
A,B,AB
0.5
A
0
duo ulcer gas ulcer stom ulcer anaemia
disease
Can you apply what you
have learnt on

Mutations and Selection

to
Migration?
Balanced Polymorphism
factors maintaining polymorphism
 Mechanisms That May Be Responsible For
Maintaining Polymorphisms in the Population
1. Heterozygote advantage (overdominance)
Example: Sickle cell anemia

2. Frequency-dependent selection
Example: Self-sterility in plants, Cichlids (fish) in African lakes

3. Heterogeneous environment
Example: Cepaea nemoralis, land snail, genetic cline and
application/exploitation of genetic cline to develop biogeographical maps – in
timber verification to curb illegal logging

4. Transition
Example: Biston betularia, peppered moth

5. Neutral mutation
As proposed by Kimura

Look up each of the examples in the literature, textbooks or even the internet!
 Heterozygote Advantage
• Overdominance for fitness maintains an
equilibrium gene frequency at intermediate
levels
• Heterozygote advantage is an attractive
explanation for polymorphism
• But only few examples to support this
• Haploid organisms have been found to
have as much variability as diploid
organisms – this argues strongly against
heterozygote advantage’s importance
 Frequency-dependent selection
• Having a phenotype that is rare may itself be an advantage
• The rare phenotype is favoured.
• The direction of selection is dependent on the gene
frequency - an allele at low frequency is favoured but the
same allele at high frequency is selected against.
• This leads to stable equilibrium gene frequency
• Birds and fish have been shown to take disproportionately
more of the more common type of food when offered a
choice
• This exerts frequency-dependent selection on polymorphic
prey, eg snails, giving advantage to individuals with a rare
pattern of colouration
 Heterogeneous environment
• The environment experienced by individuals of a
population is not constant: differs from place to place and
from time to time
• If one allele is advantageous in one environment and
another in a different environment, stable polymorphism
can result without heterozygotes necessarily being on
average superior.
• Selection is complex in such situation: depends on
• Dominance relations
• Individuals choose to breed in the environment to which they are
adapted
• Mating is preferentially between individuals from the same
environment or random
• etc
 Heterogeneous environment
• A relatively simple form of selection in a heterogeneous environment
results in a cline
• A cline is a gradient of gene frequency between one locality and
another

Location A Location B Location C Location D

• Clines are known to be maintained by selection favouring one allele in
one locality and another allele in another locality, with limited
migration, which allows mating only between individuals from
neighbouring parts of the cline
 Heterogeneous environment
North South
North Europeans Americans Europeans Asians
0.6

0.5
sp24
Rare Allele Frequency

c
0.4 d
X+
0.3 h
z

0.2

0.1

S'pore Indians
South Asians

S'pore Chinese
Chinese (China)

Japanese

Javanese
Blacks (USA)
Norwegians

Canadians

Whites (USA)

Italians
Russians
French
Swedes
Finns

Danes

Britons

Irish

Jews

Taiwanese
Populations

Allele frequencies (weighted averages) of the

apolipoproteinB gene in the various populations of the
world clustered according to geographical locations.
 Transition

• Polymorphisms seen at present might possibly be transitional

stages in the evolutionary replacement of one allele by another,
which has become more advantageous through some
environmental change in the past
• Explain only very few polymorphisms
• Eg. Study by Kettlewell on industrial melanism in the moth,
Biston betularia, a modern example of natural selection
• The moth is predated on by birds which hunt by day, one mutant
carbonaria is very dark, whereas the typical is much lighter.
• Since the industrial revolution areas in UK and Europe the
carbonaria form is the common type.
• This is because it is well camouflaged against the darkened tree
trunks in industrial areas.
 Transition

Biston betularia (peppered moth)

Dark variety
(mutant – carbonaria)

Light
variety

Melanic and typical forms of the peppered moth

a) On a lichen-covered tree b) On a soot covered trunk
 Transition
Birmingham-polluted Dorset-unpolluted

Brooker Pg 726

A comparison of the prevalence of the carbonaria

mutant and the typical morph of the moth, B.
betularia in polluted and unpolluted area
 Neutral mutation

• Selection force not responsible for polymorphism

(unlike previous 4 mechanisms)
• Polymorphism merely results from balance
between mutation and loss by chance, which
depends on population size
 What you are expected to know by now
POPULATIONS IN EQUILIBRIUM
Hardy-Weinberg Equilibrium
Single gene locus (autosomal, additive gene action) (e.g. MN blood group)
Gene frequencies
Single gene locus, 2 alleles (autosomal, codominance)
Single gene locus, 2 alleles (autosomal, complete dom.)
Single gene locus, multiple alleles (autosomal)
Single gene locus, sex-linked

NON RANDOM MATING

POPULATION GENETIC FORCES THAT CHANGE ALLELE FRQUENCIES

Mutation
One-way recurrent mutation
Two-way recurrent mutation
Selection
Selection against recessive gene
Selection favouring heterozygotes (overdominance)
Migration (not covered, but do you know how to apply the same principles!!!)
Genetic Polymorphism