04

PRINCIPLE OF INHERITANCE AND

VARIATION
Have you ever wondered that why an elephant gives rise to a baby
elephant and not any other animal? Why seeds of mango give rise to a
mango tree and not an orange or a mixed fruit tree? So what’s inside that
seed which enables growth of mango tree? Do you ever think why
someone is so tall and other is dwarf, one is fair one is not, one eats
everything but still so lean but one drinks water and swells like a balloon.
So what is the reason behind all this discrimination?
For the sake of answering such questions, gave rise to a new branch of
biology that is Genetics.
But before going into any technical terms let’s talk about something we
asked above, we asked about the colour, height, body shape etc. all these
are physical properties which in this branch are known as Phenotypic
characters(or traits). Everybody have their somewhat unique
characters but if we are generally talking about characters it includes
many sub branches but mainly we have divided characters into two
classes (1) Inherited traits and (2) Acquired traits.
Inherited traits are such traits which are transferred from one
generation, which is carried from parent by a gamete. These gametes
contain special structures known as chromosome which is a condensed
form of DNA which contains gene (gene is the unit of inheritance which
controls the expression of a character in cooperation with other genes
and environment, chemically gene is a segment of DNA called cistron
that has a particular function). This gives rise to a new term known as
Heredity. Heredity is the transmission of genetic characters from parent
to their offspring. It is also known as Inheritance.
Acquired traits are such traits which are learned during life time, ex-
swimming, cycling, playing PUBG etc.
But while the characters or traits are directly transferred from
parent to the offspring but still the offspring is not identical to the
parent due to mixing up of the genes of the two parent during
sexual reproduction. This difference among all the individual is known
as Variation. The degree of variation can vary…
Now after knowing all this basic stuff we can now give a proper definition
to genetics.
So genetics is a branch of biology that deals with the study of heredity
and variations. Term was given by William Bateson (1906).
In this chapter we will be focusing on the sub branch of genetics that is
called Transmission genetics. It deals with the topics related to
transmission of genes from one generation to the next. It is also called
classical or Mendelian genetics. In next chapter we will be studying
about the molecular genetics.
So in this chapter that concerns with the transmission of traits or
biologically speaking genes, we will study the development of this very
important branch of biology. Simple put the development of this branch
can be divided into three phases (1) Pre-Mendelian development (2)
Mendelian theory of inheritance and (3) Post-mendelian development.

PRE-MENDELIAN DEVELOPMENT
The theory and principles of genetics that we see today are not
formulated overnight but a result of observations of loads of people. Early
agriculturists (8000-10000 B.C.E) knew that the cause of variation is
hidden inside the sexual reproduction, that’s how they successfully bred
domesticated varieties from wild plants and animals through selective
crossing and artificial selection.
So way before Mendelian laws, a number of view-points were put forward
to explain transmission of characters from parents to offspring. They are
often called theories of blending inheritance as they believed that
characters of the parents blended or got mixed during their transmission
to the offspring.
Some of the theories are explained below-
1. Moist Vapour Theory- Pythagoras proposed that, during coitus moist
vapours from all parts of a male’s body gave rise to a similar body in
female’s womb.
2. Fluid Theory- Aristotle suggested that male semen is highly purified
blood and female’s menstrual fluid was female semen which is not so
pure. The two fluids combine during coitus, hence female semen provides
‘inert’ fluid for the formation of embryo and male semen gave form and
vitality to embryo.
3. Preformation theory- It states that organism is already present, i.e.
preformed in the egg or sperm in a miniature form called homunculus.
Fertilization is required for growth. Sperms were first observed for the
first time by Leeuwenhoek in 1672, then this preformation theory was
proposed by Swammerdam in 1679. But eventually discarded by Wolff
who suggested that organs are formed step by step (theory of
epigenesis).
4. Particulate Theory- According to this heredity is controlled by
minute particles which come from all parts of the body to the
reproductive organs.
5. Theory of of continuity of Germplasm- Weismann (1892)
proposed this theory, according to this theory germplasm (protoplasm of
germ cells) is “immortal” and is passed from generation to generation.
Somatoplasm (protoplasm of somatic cells) that forms the body is ‘mortal’
and perishes with the organism dies.
But eventually these theories were discarded due to evidences that
were against this theory of blending inheritance.
As the theory suggests that traits of parents blends equally so this means
that if a person with fair skin marries with a person of dark complexion
will have a baby of brown colour, which is we all know is not true.
So there was an eminent need of a new theory which can answer all such
questions.
Then came a person who on his own changed the way we look at
transmission genetics that was Gregor Johann Mendel.

MENDELIAN THEORY OF INHERITANCE

Gregor Johann Mendel is also known as father of genetics because he
was the first to demonstrate the mechanism of transmission of charaters
from one generation to the next. He also gave some generalisation or
pattern which were later raised to the status of principles or laws of
inheritance. They constitute the foundation of genetics.
For 7 years (1856-1863), he carried out hybridisation experiments on
garden pea (Pisum sativum). For the first time, logic and mathematics
were applied to problems of biology. His experiment had a large sampling
size, which gave greater credibility to the data that he collected. After
continuous experiment on successive generations of his test plants,
proved that his result pointed the general rules of inheritance.
His paper “Experiments in Plant Hybridisation” was published in the
“Annual Proceedings of Brunn Natural Science Society” in 1866.
Mendel died in 1884 without getting any recognition for his work.

Mendel’s Experiments
As said before Mendel selected Garden pea (2n=14) for his experiments.
He investigated characters in the garden pea plant that were manifested
as two opposing traits, eg. Tall or Dwarf, yellow or green seeds etc. (rest
in the table)
So why garden pea? The reason behind choosing garden pea as an
experiment subject had many advantages such as
(1) Pea plants showed a number of easily
detectable contrasting character.
(2) For preventing contamination that could
easily alter the result, Mendel has to be very
careful in choosing only the true breeding
or Pure lines (A true breeding line is one
that, having undergone continuous self-
pollination).
(3) The pure varieties are easily available as the flower remain closed and
in most cases it self- pollinates this allows controlled breeding, but they
can be manually cross bred.
(4) It has a small life span of 3 months.
(5) A large number of seeds are produced per plant.
(6) Plant does not require special care, except at the time of pollination.

EXPERIMENTAL TECHNIQUES OF MENDEL

Three steps were involved In Mendel’s experimental technique. These
were Selection of pure parent plants, Hybridization of pure plants
for F1 generation and lastly self-breeding the F 1 generation for F2
and F3 generations.
1. Selection of Pure parent Plants.
Mendel selected 7 pairs of pure varieties of pea as a starting material for
his experiments, on self-pollination or self-breeding, a pure variety gives
rise to offspring having similar trait eg. Tall variety with tall offspring, a
violet variety with violet flowered offspring. These true breeding plants
were formed Parent (P) generation.
2. Hybridisation of Pure plants for F1 generation.
Crossing or mating of two varieties of plants and animals is known as
hybridisation. Plants with contrasting traits were cross pollinated. As
we studied earlier that pea flowers mostly remain closed so they have to
be manually cross bred for that the technique we studied in chapter 2
artificial hybridisation was used. He then collected the seeds produced as
a result of this cross and grew them to generate plants of first hybrid
generation or as we call it F1 (Filial 1) progeny.

3. Self-breeding in hybrid plants for F2 and F3 generation.

The plants of F1 generation were allowed to perform self-pollination, and
then obtained seeds from them and raised them as F2 and F3
generations.

MENDEL’S MONOHYBRID CROSS

A cross between two parents that differ in only one heritable character is
called monohybrid cross.
In one such experiment, He crossed tall and dwarf pea plants to study the
inheritance of one gene.
Then these pure parent plants produced plants which he collected and
grew them to generate plants of the first hybrid generation. This
generation is called the Filial 1 progeny or F1.
He observed that all the plants of F1 generation were tall, none were
dwarf. He made same observations for the other pairs of traits, he found
that F1 generation resembled one of the parent and that the trait of the
other parent was not seen in them.

Then he self-pollinated the tall F1 plants and the observations were very
different from what was expected, in Filial 2 some of the offspring were
“dwarf”. The characters which were not seen in the F 1 generation were
now expressed. The proportions of plants that were dwarf were 1/4 th
while 3/4th of them were tall. The tall and dwarf traits were identical to
their parental type and did not show any blending, that is all the offspring
were either tall or dwarf, none of them were in between height.
So the result concluded that, only one parental character was
expressed in the F1 generation while at F2 stage both the traits
were expressed in the proportion of 3:1. The contrasting traits do
not show any blending.

RESULT OF MENDEL’S MONOHYBRID CROSS

Based on these observations, Mendel proposed that something was being
stably passed down unchanged, from parent to the offspring through the
gametes, over successive generations. He called these things as
‘factors’. Now we know them as ‘Genes’, therefore genes are the unit of
inheritance. They contain the information that is required to express a
particular trait in an organism.
As in the above experiment some plants were tall and some were dwarf,
so Mendel concluded that there should be two types of factors that codes
for such contrasting characters, so there comes the concept of Alleles,
Alleles are those genes which code for contrasting pair of traits.
Hence different forms of same gene.
So after the introduction of the concept of allele or different form of the
same gene, then there must be different and unique notations for the
alleles. So in the above experiment the capital letter is used for trait that
is expressed in F1 stage and small letter for the non-expressed trait. For
example- taking the same cross above shown between tall and dwarf
plant.
T = for the tall trait
t= for the dwarf trait
T and t are alleles of each other

Hence in plants, the pair of alleles the pair of alleles for height would be
TT, Tt and tt.
In Pure breeding or parent plant the allelic pair of genes for
height are identical i.e. homozygous TT and tt.
Hence TT and tt were referred as genotype, and Tall and dwarf are
referred as phenotype.
As Mendel found the phenotype of the F1 heterozygote Tt to be exactly
like the TT parent in appearance, he proposed that in a pair of dissimilar
factors, one dominates the other (as in the F1) and hence is called the
dominant factor while the other factor is recessive.
In this case T (for tallness) is dominant over t (for dwarfness), that
is recessive.
He observed identical behaviour for all the other characters/trait-pairs
that he studied.

From the observation that the recessive parental trait is expressed

without any blending in the F2
generation, we can infer that, when the tall and dwarf plant produce
gametes, by the process of meiosis, the alleles of the parental pair
separate or segregate from each other and only one allele is transmitted
to a gamete.
This segregation of alleles is a random process and so there is a 50 per
cent chance of a gamete containing either allele, as has been verified by
the results of the crossings.

MONOHYBRID CROSS
The production of gametes by the parents, the formation of the zygotes,
the F1 and F2 plants can be understood from a diagram called Punnett
Square. It was developed by a British geneticist, Reginald C. Punnett.
It is a graphical representation to calculate the probability of all possible
genotypes of offspring in a genetic cross.
The possible gametes are written on two sides, usually the top row and
left columns. All possible
combinations are represented in boxes below in the squares, which
generates a square output form.
The Punnett Square shows the parental tall TT (male) and dwarf tt
(female) plants, the gametes
produced by them and, the F1 Tt progeny. The F1 plants of genotype Tt
are self-pollinated. The F1 plant of the
genotype Tt when self-pollinated,
produces gametes of the genotype T and t
in equal proportion.
When fertilisation takes place, the pollen
grains of genotype T have a 50 per cent
chance to pollinate eggs of the genotype
T, as well as of genotype t. Also pollen
grains of genotype t have
a 50 per cent chance of pollinating eggs of
genotype T, as well as of genotype t. As a
result of random fertilisation, the resultant
zygotes can be of the genotypes TT, Tt or
tt.
From the Punnett square it is easily seen
that 1/4th of the random fertilisations lead
to TT, 1/2 lead to Tt and 1/4th to tt.
Though the F1 have a genotype of Tt, but
the phenotypic character seen is ‘tall’. At
F2,
3/4th of the plants are tall, where some of
them are TT while others are Tt.
Externally it is not possible to distinguish
between the plants with the genotypes TT
and Tt. Hence, within the genotypic pair
Tt only one character ‘T’ tall is expressed. Hence the character T or ‘tall’
is said to dominate over the other allele t or ‘dwarf’ character. It is thus
due to this dominance of one character over the other that all the F1 are
tall (though the genotype is Tt) and in the F2 3/4th of the plants are tall
(though genotypically 1/2 are Tt and only 1/4th are TT).
This leads to a phenotypic ratio of 3/4th tall: (1/4 TT + 1/2 Tt) and 1/4th
tt, i.e., a 3:1 ratio, but a genotypic ratio of 1:2:1.
So it is clear from above that finding genotype is not possible by just
looking at the plant, as one factor or say allele dominates over the other
hence the phenotypic result of both TT and Tt are the same as tall. Hence
a process was formulated to determine the genotype at F 2, this process is
known as Test cross.

TEST CROSS
Test cross is carried out to determine the genotype of a plant from F 2
generation, in this the plant form filial 2 is crossed with a dwarf plant. So
basically instead of self-crossing the plant is crossed with the recessive
parent. The progenies can be analysed to determine the genotype of the
parent (whose genotype is to be determined).
So let’s understand this with an example
For this let’s consider the flower colour as a reference trait, in pea plant
the dominant trait is violet colour and recessive is white. So it should be
pretty clear by now that the plant bearing white will have a homozygous
recessive genotype in this case i.e. ‘vv’ so when we will cross this
recessive parent with the ‘plant’ then there will be two cases which are
explained in the diagram below.

So from above experiments the conclusion that Mendel reached were-

1) Mendel proposed that something was transferred unchanged from
parents to the offspring through the gametes, over successive
generations, Mendel named them as ‘Factor’.
2) As F1 plants were not of intermediate height, this proves that theory of
blending inheritance was wrong.
 3) The factors which are being passed occur in pair. Out of the pair the
two unit factors can be similar or dissimilar, if dissimilar one of the factor
will be dominant on the other and the phenotype will be according to the
dominant genotype
4) Factors which occur in pair
segregates during gamete
formation.
5) There is no mixing up
between the two factors
6) The two traits of the
character appear in F2
generation in ratio of 3
dominant to 1 i.e. 3:1 is called
monohybrid ratio.

Mendel Dihybrid
Cross
Mendel also worked with and
crossed pea plants that differed in
two characters, as is seen in the
cross between a pea plant that has
seeds with yellow colour and round
shape and one that had seeds of
green colour and wrinkled shape. Mendel found that the seeds resulting from the
crossing of the parents, had yellow coloured and round shaped seeds.
Thus, yellow colour was dominant over green and round shape dominant over
wrinkled. These results were identical to those that he got when he made separate
monohybrid crosses between yellow and green seeded plants and between round
and wrinkled seeded plants. Let us use the genotypic symbols Y for dominant yellow
seed colour and y for recessive green seed colour, R for round shaped seeds and r
for wrinkled seed shape. The genotype of the parents can then be written as RRYY
and rryy. The cross between the two plants can be written down the diagram
showing the genotypes of the parent plants. The gametes
RY and ry unite on fertilisation to produce the F 1 hybrid RrYy. When Mendel self-
hybridised the F1 plants he found that 3/4th of F2 plants had yellow seeds and 1/4th
had green. The yellow and green colour segregated in a 3:1 ratio. Round and
wrinkled seed shape also segregated in a 3:1 ratio; just like in a monohybrid cross.

Results of Mendel’s finding

(i) Four findings of plants: Four types of plants were produced in the F2 generation
in the ratio 9:3:3:1

(ii) The formation of four types of individuals in the F2 generation of a Dihybrid

cross, shows that the two factors are selected or assorted independently, no mixing
up between the factors.

With all this hard-work for 7 long years, and over that two years of data compilation
Mendel managed to publish his work under the name “Experiments in plant

So what were the reasons for such ground breaking discovery to be left unknown for
34 long years?
It was because
(1) The communication was not easy at that time, and the circulation of the publishing
society was not much.
(2) His concept of genes (or factors) as stable and discrete units that controlled the
expression of traits and of the pair of alleles which did not blend with each other was
hybridisation” in the “Annual proceedings of Brunn natural science society”
in 1866. Yet he didn’t get any recognition for his work.

REDISCOVERY OF MENDEL’S WORK

Mendel died in 1884 long before his work came to be recognised. It was in 1900
that three scientists independently rediscovered the principles of heredity
already worked out by Mendel. They were Hugo de Vries of Holland, Carl
Correns of Germany and Erich von Tschermak-Seysenegg of Austria.
Hugo de Vries found out the paper of Mendel and got published in ‘Flora’ in
1901. Bateson, Punnet and other scientists found that Mendel’s work was also
applicable to animals.
SO THERE ARE SOME POINTS TO REMEMBER
(1) Mendel himself did not proposed any genetical principles or law. He
gave conclusive theoretical and statistical explanations for his
hybridisation experiments in his research paper.
(2) It was Correns (1901) who thought that Mendel’s discovery could be the
Laws of heredity which were named after Mendel’s name.
* Correns called Law of Segregation the first law of inheritance and law
of independent assortment as the second law of inheritance. And law of
dominance is not given any number.
(3) Mendel confirmed his findings in pea with those in rajma
(4) Use terms allele/alleles instead of factor while describing the Mendel’s law of
inheritance.

MENDEL’S LAWS OF INHERITANCE

The study of the Mendel’s laws of inheritance is called Mendelism. There are three
Mendel’s Laws of inheritance: Law of Dominance, Law of Segregation (both laws
are based upon monohybrid cross) and Law of independent Assortment (based on
dihybrid cross).

Every character is controlled by a gene that has at least two alleles, this is known as
Monogenic inheritance. Study of inheritance of single gene of a character at a
time is called inheritance of one gene.

Law of Dominance
(i) Characters are controlled by discrete units called factors.
(ii) Factors occur in pairs.
(iii) In a dissimilar pair of factors one member of the pair dominates
(dominant) the other (recessive).

The law of dominance is used to explain the expression of only one of the parental
characters in a monohybrid cross in the F1 and the expression of both in the F 2. It
also explains the proportion of 3:1 obtained at the F 2.

Law of Segregation

This law is based on the fact that the alleles do not show any blending and that
both the characters are recovered as such in the F2 generation though one of
these is not seen at the F1 stage. Though the parents contain two alleles during
gamete formation, the factors or alleles of a pair segregate from each other such
that a gamete receives only one of the two factors. Of course, a homozygous
parent produces all gametes that are similar while a heterozygous one produces
two kinds of gametes each having one allele with equal proportion.

The Law of segregation is the most fundamental principle of heredity that with
no exception.

Law of Independent Assortment

The law states that ‘when two pairs of traits are combined in a hybrid,
segregation of one pair of characters is independent of the other pair of
characters’.

The laws of Mendel or Mendelism has

certain limitations or you can say have
certain exception such as LOIA have an
exception known as Linkage (which will
be discussed later).

Exceptions to the Law of

Dominance
1- Incomplete Dominance
When experiments on peas were repeated
using other traits in other plants, it was found
that sometimes the F1 had a phenotype that
did not resemble either of the two parents
and was in between the two. The inheritance
of flower colour in the dog flower
(snapdragon or Antirrhinum sp.) is a good
example to understand incomplete
dominance. In a cross between true-breeding
red-flowered (RR) and true-breeding white-
flowered plants (rr), the F1 (Rr) was pink.
When the F1 was self-pollinated the F2
resulted in the following ratio 1 (RR) Red: 2
(Rr) Pink: 1 (rr) White. Here the genotype ratios were exactly as we
would expect in any mendelian monohybrid cross, but the phenotype
ratios had changed from the 3:1 dominant : recessive ratio. What
happened was that R was not completely dominant over r and this made
it possible to distinguish Rr as pink from RR (red) and rr (white).

Explanation of the concept of dominance:

What exactly is dominance? Why are some alleles dominant and some recessive?
To tackle these questions, we must understand what a gene does. Every gene, as
you know by now, contains the information to express a particular trait. In a
diploid organism, there are two copies of each gene, i.e., as a pair of alleles.
Now, these two alleles need not always be identical, as in a heterozygote. One of
them may be different due to some changes that it has undergone (about which
you will read further on, and in the next chapter) which modifies the information
that particular allele contains.

Let’s take an example of a gene that contains the information for producing an
enzyme. Now there are two copies of this gene, the two allelic forms. Let us
assume (as is more common) that the normal allele produces the normal enzyme
that is needed for the transformation of a substrate S. Theoretically, the
modified allele could be responsible for production of –
(i) the normal/less efficient enzyme, or
(ii) a non-functional enzyme, or
(iii) no enzyme at all
In the first case, the modified allele is equivalent to the unmodified allele, i.e., it
will produce the same phenotype/trait, i.e., result in the transformation of
substrate S. Such equivalent allele pairs are very common. But, if the allele
produces a non-functional enzyme or no enzyme, the phenotype may be effected.
The phenotype/trait will only be dependent on the functioning of the unmodified
allele. The unmodified (functioning) allele, which represents the original
phenotype is the dominant allele and the modified allele is generally the
recessive allele. Hence, in the example above the recessive trait is seen due to
non-functional enzyme or because no enzyme is produced.

For example, starch synthesis in pea seeds is controlled by one gene. It has two
alleles (B and b). Starch is synthesised effectively by BB homozygotes and
therefore, large starch grains are produced. In contrast,
bb homozygotes have lesser efficiency in starch synthesis and produce smaller
starch grains. After maturation of the seeds, BB seeds are round and the bb
seeds are wrinkled. Heterozygotes produce round seeds, and so B seems to be
the dominant allele. But, the starch grains produced are of intermediate size in
Bb seeds. So if starch grain size is considered as the phenotype, then from this
angle, the alleles show incomplete dominance.
Therefore, dominance is not an autonomous feature of a gene or the product
that it has information for. It depends as much on the gene product and the
production of a particular phenotype from this product as it does on the
particular phenotype that we choose to examine, in case more than one
phenotype is influenced by the same gene.

Co-Dominance
Till now we were discussing crosses where the F1 resembled either of the
two parents (dominance) or was in-between (incomplete dominance). But,
in the case of co-dominance the F1 generation resembles both parents. A
good example is different types of red blood cells that determine ABO
blood grouping in human beings.
ABO blood groups are controlled by the gene I. The plasma membrane of
the red blood cells has sugar polymers that protrude from its surface and
the kind of sugar is controlled by the gene.
The gene (I) has three alleles IA, IB and i. The alleles IA and IB produce a
slightly different form of the sugar while allele i does not produce any
sugar. Because humans are diploid organisms, each person possesses
any two of the three I gene alleles. IA and IB are completely dominant over
i, in other words when IA and i are present only IA expresses (because I
does not produce any sugar), and when IB and i are present IB expresses.
But when IA and IB are present together they both express their own types
of sugars: this is because of co-dominance. Hence red blood cells have
both A and B types of sugars. Since there are three different alleles, there
are six different combinations of these three alleles that are possible, and
therefore, a total of six different genotypes of the human ABO blood
types.
(a) Person with I0I0 alleles will have blood group O because they don’t have
antigen A nor antigen B.
(b) Person with IAIA and IAI0 alleles will have blood group A because allele IA
is dominant on allele I0
(c) Person with IBIB and IBI0 alleles will have blood group B because allele IB
is dominant on allele I0
(d) Person with IAIB alleles will have blood group AB because allele IA is co-
dominant with IB.

Multiple Allele
When there are more than two forms (allele) of gene in a population occupying
the same locus on a chromosome are known as multiple alleles.
Human ABO blood grouping is an example of it.

Pleiotropy
While a gene may have multiple alleles and thus give multiple genotypes, one
gene may control several phenotypes. For example the recessive gene for white
eye in Drosophila when present in the homozygous condition affects several
other features such as wing shape and shape of abdomen. Thus, a white eyed
Drosophila is also born with vestigeal wings and curled abdomen.

Polygenic or quantitative inheritance

When a trait (feature or character) is controlled by a single gene representing
an allelic pair it is termed monogenic inheritance. However, many traits or
features are controlled by a number of different genes present at different loci
on the same chromosome or different chromosomes. For example, the height
and skin colour of humans and the kernel colour of wheat results from
the combined effect of several genes, none of which are singly dominant.
Polygenes affecting a particular trait are found on different loci on many
chromosomes. Each of these genes has equal contribution and cumulative effect.
Three to four genes contribute towards formation of the pigment in the skin of
humans. So there is a continuous variation in skin colour from very fair to very
dark. Such an inheritance controlled by many
genes having additive or cumulative effect in terms of expression of the
phenotypic character, is termed as quantitative inheritance or polygenic
(poly meaning or due to many genes) inheritance.
Chromosomal theory of inheritance
In 1900, three Scientists (de Vries, Correns and von Tschermak) independently
rediscovered Mendel’s results on the inheritance of characters. Also, by this
time due to advancements in microscopy that were taking place, scientists were
able to carefully observe cell
division. This led to the discovery
of structures in the nucleus that
appeared to double and divide just
before each cell division. These
were called chromosomes
(colored bodies, as they were
visualised by staining). By 1902,
the chromosome movement during
meiosis had been worked out.
Walter Sutton and Theodore
Boveri noted that the behaviour of
chromosomes was parallel to the
behaviour of genes and used
chromosome movement to explain
Mendel’s laws. Recall that you
have studied the behaviour of chromosomes during mitosis (equational division)
and during meiosis (reduction division). The important things to remember
are that chromosomes as well as genes occur in pairs. The two alleles of
a gene pair are located on homologous sites on homologous
chromosomes.
During Anaphase of meiosis I, the two chromosome pairs can align at the
metaphase plate independently of each other. To understand this, compare the
chromosomes of four different colour in the left and right columns. In the left
column (Possibility I) orange and green is segregating together. But in the right
hand column (Possibility II) the orange chromosome is segregating with the red
chromosomes. Sutton and Boveri argued that the pairing and separation of a
pair of chromosomes would lead to the segregation of a pair of
factors they carried. Sutton united the knowledge of chromosomal segregation
with Mendelian principles and called it the chromosomal theory of inheritance.

EXPERIMENTAL VERIFICATION OF
CHROMOSOMAL THEORY OF INHERITANCE
Following this synthesis of ideas, experimental verification of the chromosomal
theory of inheritance by Thomas Hunt Morgan and his colleagues, led to
discovering the basis for the variation that sexual reproduction produced.
Morgan worked with the tiny fruit flies, Drosophila melanogaster which
were
found very suitable for such studies. They could be grown on simple synthetic
medium in the laboratory. They complete their life cycle in about two weeks,
and a single mating could produce a large number of progeny flies. Also, there
was a clear differentiation of the sexes – the male and female flies are easily
distinguishable. Also, it has many types of hereditary variations that can be seen
with low power microscopes.

LINKAGE AND RECOMBINATION

Morgan carried out several dihybrid crosses in Drosophila to study genes that
were sex-linked. The crosses were similar to the dihybrid crosses carried out by
Mendel in peas.

For example Morgan hybridised yellow-bodied, white-eyed females to

brown-bodied, red-eyed males and intercrossed their F1 progeny. He
observed that the two genes did not segregate independently of each other and
the F2 ratio deviated very significantly from the 9:3:3:1 ratio (expected when
the two genes are independent).
Morgan and his group knew that the genes were located on the X-
chromosome and saw quickly that when the two genes in a dihybrid
cross were situated on the same chromosome, the proportion of parental
gene combinations were much higher than the non-parental type.
Morgan attributed this due to the physical association or linkage of the two
genes and coined the term linkage to describe this physical association of genes
on a chromosome and the term recombination to
describe the generation of non-parental gene combinations.

Morgan and his group also found that even

when genes were grouped on the same
chromosome, some genes were very tightly
linked (showed very low recombination)
(Cross A) while others were loosely linked
(showed higher recombination) (Cross B).
For example he found that the genes white
and yellow were very tightly linked and
showed only 1.3 per cent recombination
while white and miniature wing showed 37.2
per cent recombination.
His student Alfred Sturtevant used the
frequency of recombination between gene
pairs on the same chromosome as a measure
of the distance between genes and ‘mapped’
their position on the chromosome. Today
genetic maps are extensively used as a
starting point in the sequencing of whole
genomes as was done in the case of the
Human Genome Sequencing

CHROMOSOMES AND
SEX DETERMINATION
Sex of the unborn individuals is determined
in different ways in different kinds of organisms.
In some diploid organisms, specific chromosomes have a role in sex
determination. Such chromosomes are called sex chromosomes and the rest of
the chromosomes of a set are called autosomes. If sex chromosomes are
morphologically similar (i.e. XX) in an individual, the individual is termed
homogametic. Such individuals, produce only one kind of gametes (containing
X). For example: all eggs of the human female contain an X chromosome and
autosomes. So human female is termed as homogametic.

SEX DETERMINATION
The mechanism of sex determination has always been a puzzle before the
geneticists. The initial clue about the genetic chromosomal mechanism of sex
determination can be traced back to some of the experiments carried out in
insects. In fact, the cytological observations made in a number of insects led to
the development of the concept of genetic/chromosomal basis of sex-
determination.
Henking (1891) could trace a specific nuclear structure all through
spermatogenesis in a few insects, and it was also observed by him that 50 per
cent of the sperm received this structure after spermatogenesis, whereas the
other 50 per cent sperm did not receive it. Henking gave a name to this
structure as the X body but he could not explain its significance. Further
investigations by other scientists led to the conclusion that the ‘X body’ of
Henking was in fact a chromosome and that is why it was given the name X-
chromosome.
It was also observed that in a large number of insects the mechanism of sex
determination is of the
XO type, i.e., all eggs bear an additional X-chromosome besides the other
chromosomes (autosomes). On the other hand, some of the sperms bear the X-
chromosome whereas some do not.
Eggs fertilised by sperm having an X-chromosome become females and, those
fertilised by sperms that do not have an X-chromosome become males.
Due to the involvement of the X-chromosome in the determination of sex, it was
designated to be the sex
chromosome, and the rest of the
chromosomes were named as
autosomes.
Grasshopper is an example of
XO type of sex determination
in which the males have only one
X- chromosome besides the
autosomes, whereas females have a pair of X-chromosomes. These observations
led to the investigation of a number of species to understand the mechanism of
sex determination. In a number of other insects and mammals including man, XY
type of sex determination is seen where both male and female have same
number of chromosomes.

SEX DETERMINATION IN HONEY BEES

Honey bees have a unique method of sex determination. In honey bees, fertilised
eggs emerge as females and
unfertilised eggs develop into males.
Since fertilised eggs and also females
are diploid and unfertilised eggs and
males haploid, sex determination in
honey bees is referred to as
haplodiploidy-sometimes also called
arrhenotoky.
The sex is determined by the number of
sets of chromosomes an individual
receives. The male, which is called a
drone, is produced from unfertilized
haploid eggs. And thus, male
honeybees contain a single set of
chromosomes. The female honeybees,
which are worker bees and queen bees, are produced from fertilized eggs and
therefore are diploid. They contain two sets of chromosomes. In this case, only
females are produced by sexual reproduction. It is very interesting in honey
bees that males have no father and cannot have sons but have a grandfather and
can have grandsons.

MALE HETEROGAMETY AND FEMALE

HETEROGAMETY
Among the males an X-chromosome is present but its counter-part is distinctly
smaller and called the Y-chromosome. Females, however, have a pair of X-
chromosomes. Both males and females bear same number of autosomes. Hence,
the males have autosomes plus XY, while female have autosomes plus XX. In
human beings and in Drosophila the males have one X and one Y chromosome,
whereas females have a pair of X-chromosomes besides autosomes.
In the above description you have studied about two types of sex determining
mechanisms, i.e., XO type and XY type. But in both cases males produce two
different types of gametes, (a) either with or without
X-chromosome or (b) some gametes with X-chromosome and some with Y-
chromosome. Such types of sex determination mechanism is designated to be
the example of male
heterogamety. In
some other
organisms, e.g.,
birds, a different
mechanism of sex
determination is
observed. In this case
the total number of
chromosome is same in both males and females. But two different types of
gametes in terms of the sex chromosomes, are produced by females, i.e.,
female heterogamety. In order to have a distinction with the mechanism of sex
determination described earlier, the two different sex chromosomes of a female
bird has been designated to be the Z and W chromosomes. In these organisms
the females have one Z and one W chromosome, whereas males have a pair of Z-
chromosomes besides the autosomes.

MUTATION
Mutation is a phenomenon which results in alteration of DNA sequences and
consequently results in changes in the genotype and the phenotype of an
organism. In addition to recombination, mutation is another phenomenon that
leads to variation in DNA.
As you will learn in Chapter 6, one DNA helix runs continuously from one end to
the other in each chromatid, in a highly supercoiled form. Therefore loss
(deletions) or gain (insertion/duplication) of a segment of DNA, result in
alteration in chromosomes. Since genes are known to be located on
chromosomes, alteration in chromosomes results in abnormalities or
aberrations. Chromosomal aberrations are commonly observed in cancer cells.
In addition to the above, mutation also arise due to change in a single base pair
of DNA. This is known as point mutation. A classical example of such a mutation
is sickle cell anemia. Deletions and insertions of base pairs of DNA, causes
frame-shift mutations.
The mechanism of mutation is beyond the scope of this discussion, at this level.
However, there are many chemical and physical factors that induce mutations.
These are referred to as mutagens. UV radiations can cause mutations in
organisms – it is a mutagen.
GENETIC DISORDERS
Pedigree Analysis
The idea that disorders are inherited has been prevailing in the human society
since long. This was based on the heritability of certain characteristic features
in families. After the rediscovery of Mendel’s work the practice of analysing
inheritance pattern of traits in human beings began. Since it is evident that
control crosses that can be performed in pea plant or some other organisms, are
not possible in case of human beings, study of the family history about
inheritance of a particular trait provides an alternative.
Such an analysis of traits in a several of generations of a
family is called the pedigree analysis. In the pedigree
analysis the inheritance of a particular trait is represented
in the family tree over generations. In human genetics,

pedigree study provides a strong tool, which is utilised to trace the inheritance
of a specific trait, abnormality or disease. Some of the important standard
symbols used in the pedigree analysis have been shown.
As you have studied in this chapter, each and every feature in any organism is
controlled by one or the other gene located on the DNA present in the
chromosome. DNA is the carrier of genetic information. It is hence transmitted
from one generation to the other without any change or alteration. However,
changes or alteration do take place occasionally. Such an alteration or change in
the genetic material is referred to as mutation. A number of disorders in human
beings have been found to be associated with the inheritance of changed or
altered genes or chromosomes.

MENDELIAN DISORDERS
Broadly, genetic disorders may be grouped into two categories – Mendelian
disorders and Chromosomal disorders. Mendelian disorders are mainly
determined by alteration or mutation in the single gene. These disorders
are transmitted to the offspring on the same lines as we have studied in the
principle of inheritance. The pattern of inheritance of such Mendelian
disorders can be traced in a family by the pedigree analysis. Most common
and prevalent Mendelian disorders are Haemophilia, Cystic fibrosis, Sickle-
cell anaemia, Colour blindness, Phenylketonuria, Thalassemia, etc.
It is important to mention here that such Mendelian disorders may be dominant
or recessive. By pedigree analysis one can easily understand whether the trait in
question is dominant or recessive. Similarly, the trait may also be linked to the
sex chromosome as in case of haemophilia. It is evident that this X-linked
recessive trait shows transmission from carrier female to male progeny. A
representative pedigree is shown in diagram for dominant and recessive traits.

Haemophilia: This sex linked recessive disease, which shows its

transmission from unaffected carrier female to some of the male progeny has
been widely studied. In this disease, a single protein that is a part of the cascade
of proteins involved in the clotting of blood is affected.
Due to this, in an affected individual a simple cut will result in non-stop
bleeding. The heterozygous female (carrier) for haemophilia may transmit the
disease to sons. The possibility of a female becoming a haemophilic is extremely
rare because mother of such a female has to be at least carrier and the father
should be haemophilic (unviable in the later stage of life). The family pedigree of
Queen Victoria shows a number of haemophilic descendents as she was a carrier
of the disease.

Sickle-cell Anaemia: This is an autosome linked recessive trait that can

be transmitted from parents to the offspring when both the partners are carrier
for the gene (or heterozygous). The disease is controlled by a single pair of
allele, HbA and HbS. Out of the three possible genotypes only homozygous
individuals for HbS (HbSHbS) show the diseased phenotype.
Heterozygous (HbAHbS) individuals appear apparently unaffected but they are
carrier of the disease as there is 50 per cent probability of transmission of the
mutant gene to the progeny, thus exhibiting sickle-cell trait. The defect is
caused by the substitution of Glutamic acid (Glu) by Valine (Val) at the sixth
position of the beta globin
chain of the haemoglobin
molecule. The substitution
of amino acid in the globin
protein results due to the
single base substitution at
the sixth codon of the beta
globin gene from GAG to
GUG. The mutant
haemoglobin molecule
undergoes polymerisation
under low oxygen tension
causing the change in the
shape
of the RBC from biconcave
disc to elongated sickle like structure

PHENYLKETONURIA: This inborn error of metabolism is also inherited as

the autosomal recessive trait. The affected individual lacks an enzyme that
converts the amino acid phenylalanine into tyrosine. As a result of this
phenylalanine is accumulated and converted into phenylpyruvic acid and other
derivatives. Accumulation of these in brain results in mental retardation. These
are also excreted through urine because of its poor absorption by kidney.

THALASSEMIA
It is a disorder in which haemoglobin is not synthesised properly. So, frequent
blood transfusions are required for survival. The defective gene is recessive and
therefore heterozygous parents may not show the disorder. The child who gets
the defective genes ‘from both the parents (homozygous recessive) suffers from
Thalassemia.
Thalassemias are a group of disorders caused by defects in the synthesis of
globin polypeptide. Absence or reduced synthesis of one of the globin chains
results in an excess of the other. In this situation free globin chains, which are
insoluble, accumulate inside the red cells and form precipitates which damage
the cell, causing cell lysis and resulting in anemia. There are two main types of
Thalassemias in which synthesis of or globin is defective. It is common in
Mediterranean, Middle East, Indian subcontinent and in south east Africa.

Alpha (α) Thalassaemia

The α Thalassaemias involve the genes HBA1 and HBA2, inherited in a
Mendelian recessive fashion. There are two gene loci and so four alleles. It is
also connected to the deletion of the 16p chromosome. α Thalassaemias result in
decreased alpha-globin production, therefore fewer alpha-globin chains are
produced, resulting in an excess of β chains in adults and excess γ chains in
newborns. The excess β chains form unstable tetramers (called Hemoglobin H or
HbH of 4 beta chains) which have abnormal oxygen dissociation curves.

Beta (β) Thalassaemia

Beta Thalassaemias are due to mutations in the HBB gene on chromosome 11 ,
also inherited in an autosomal-recessive fashion. The severity of the disease
depends on the nature of the mutation. Mutations are characterized as (βo or β
Thalassaemia major) if they prevent any formation of β chains (which is the most
severe form of β Thalassaemia); they are characterized as (β+ or β Thalassaemia
intermedia) if they allow some β chain formation to occur. In either case there is
a relative excess of α chains, but these do not form tetramers: rather, they bind
to the red blood cell membranes, producing membrane damage, and at high
concentrations they form toxic aggregates.
Delta (δ) Thalassaemia
As well as alpha and beta chains being present in hemoglobin about 3% of adult
hemoglobin is made of alpha and delta chains. Just as with beta Thalassaemia,
mutations can occur which affect the ability of this gene to produce delta chains.

COLOUR BLINDNESS (SEX- RECESSIVE TRAIT)

Colour blindness is a recessive sex-linked trait in which the eye fails to
distinguish red and green colours. The gene for normal vision is dominant. The
normal gene and its recessive allele are carried by X-chromosome. In female
colour blindness appears only when both the sex chromosomes carry the
recessive gene (Xc Xc). The females have normal vision
but function as carrier if a single recessive gene for colour blindness is present
(XXc). However, in human males the defect appears in the presence of a single
recessive gene (Xc Y) because Y chromosomes of males do not carry any gene
for colour vision. Colour blindness, like any other sex-linked trait, shows criss-
cross inheritance.
Colour blindness does not mean not seeing any colour at all, it means that those
who are colour-blind have trouble in seeing the differences between certain
colours.
Most colour-blind people can’t tell the difference between red or green. That
does not mean that they cannot do their normal work - Infact they can also drive
– they learn to respond to the way the traffic signal lights up-the red light is
generally on the top and green is on the bottom.

CHROMOSOMAL DISORDERS
The chromosomal disorders on the other hand are caused due to absence
or excess or abnormal arrangement of one or more chromosomes.
Failure of segregation of chromatids during cell division cycle results in the gain
or loss of a chromosome(s), called aneuploidy. For example, Down’s syndrome
results in the gain of extra copy of chromosome 21. Similarly, Turner’s
syndrome results due to loss of an X chromosome in human females.
Failure of cytokinesis after telophase stage of cell division results in an increase
in a whole set of chromosomes in an organism and, this phenomenon is known
as polyploidy.
This condition is often seen in plants. The total number of chromosomes in a
normal human cell is 46 (23 pairs). Out of these 22 pairs are autosomes and one
pair of chromosomes are sex chromosome.
Sometimes, though rarely, either an additional copy of a chromosome may be
included in an individual or an individual may lack one of any one pair of
chromosomes. These situations are known as trisomy or monosomy of a
chromosome, respectively. Such a situation leads to very serious consequences
in the individual. Down’s syndrome, Turner’s syndrome, Klinefelter’s syndrome
are common examples of chromosomal disorders.
Down’s Syndrome: The cause of this
genetic disorder is the presence of an
additional copy of the chromosome
number 21 (trisomy of 21). This
disorder was first described by
Langdon Down (1866). The affected
individual is short statured with small
round head, furrowed tongue and
partially open mouth. Palm is broad
with characteristic palm crease.
Physical, psychomotor and mental
development is retarded.

Klinefelter’s Syndrome : This genetic disorder is also caused due to the

presence of an additional copy of X-chromosome resulting into a karyotype of
47, XXY. Such an individual has overall masculine development however, the
feminine development (development of breast, i.e., Gynaecomastia) is also
expressed. Such individuals are sterile.

Turner’s Syndrome : Such a disorder is caused due to the absence of one of

the X chromosomes, i.e., 45 with X0, Such females are sterile as ovaries are
rudimentary beside other features including lack of other secondary sexual
characters