INHERITANCE AND VARIATION

The branch of biology that deals with the inheritance of characters from parents
to offspring is called as genetics. The word genetics was coined by William
Bateson.
Genetics is the subject that deals with the inheritance, as well as the variation of
characters from parents to offspring.
Inheritance is the process by which characters are passed on from parent to
progeny; it is the basis of heredity.
The word ‘heredity’ is taken from hereditus meaning heirship. Inheritance of
similar characters from parents.
Variation is the degree by which progeny differ from their parents.
Reasons for Mendel Success
 Gregor Johann Mendel, Austrian Monk, is known as the ‘Father of Genetics’
 Mendel organised his experiments methodically, obtained observations
systematically and analysed the obtained data mathematically applying
statistics.
 He selected garden pea plant for various reasons.
 He obtained true breeds of each character.
 He studied the offspring of not only the first generation but also the second
generation.
 Mendel studied inheritance of seven different pairs of contrasting
characters in garden pea.
 He counted the offsprings, their phenotypes and genotypes, after each cross
and then analysed the results mathematically.
 He organized his data in a simple and objective manner.
 He Conducted hybridization experiments on garden Pea plants.
 Hybridization experiment is a three step process:
1. Selection of True Breeding parents.
2. Cross pollination between true breeding parents to get First Filial
Generation F1.
3. Self-pollination or selfing of F1 plants to get Second Filial
Generation or F2
 He talked about certain factors that people did not believe in.
 His work got unrecognised initially.
  In 1900, his results were independently rediscovered by three biologists
namely, Hugo De Vries, Carl Correns and Enrich Von Tschermak.
 A few years later, W. Bateson and others confirmed Mendel’s work and
found that the same laws were applied to animals also.
 His experiments had a large sampling size, which gave greater credibility to
the data that he collected.
 The confirmation of his inferences from experiments on successive
generations of his test plants, proved that his results pointed to general rules
of inheritance rather than being unsubstantiated ideas.
Why Pea plant ?
Mendel selected pea plant as his experimental material because:
 It was easily available.
 It is easy to cultivate both in field and in Lab.
 Flowers were easy to handle.
 Flowers of pea plants remain closed till pollination.
 It showed seven pairs of contrasting characters.
 Self and cross-pollination both were easily possible in this plant.
 It has a short life cycle.
 Pure line varieties were present.
 A true breeding line is one that, having undergone continuous self-
pollination, shows the stable trait inheritance and expression for several
generations.
 Mendel selected 14 true-breeding pea plant varieties (7 characters),as pairs

Mendel’s Experiments:
  Mendel took tall and dwarf plants and made them cross and he seeds
available after the cross were planted.
 All the seeds that were planted grew into tall plants.
 These plants were called the F 1 generation or first filial generation.
 He took plants from the F 1 generation and made them to self-pollinate.
 The seeds obtained from them were again planted.
 The seeds gave rise to a new generation known as the F 2 generation i.e.,
second filial generation.
 Some of the plants of F 2 generation were tall, some were dwarf.
 The 3/4th of them were tall, 1/4th of the plants were dwarf, (3:1)
 Only one parental trait was expressed in F 1 generation and both the traits
expressed in F 2 generation.
 He used alphabets for characters e.g ‘T’ is the allele that controls tall trait
and ‘t’ is the allele that controls dwarf trait.
 Gene for homozygous tall can be represented as ‘TT’ while dwarf can be
represented as ‘tt’.
 The F 1 generation that was obtained was heterozygous (Tt). These plants
were phenotypically tall like the parent with gene TT.
 From this he concluded that T is the dominant allele which expresses itself
irrespective of the second allele present.
 In F 2 generation, tall plants with genotype TT and Tt appeared while dwarf
plants with tt gene appeared.
 He concluded that ‘t’ is the recessive allele and it can only express itself in
the presence of the same recessive allele.
He conducted experiments with other traits – he found that the F1 always
resembled either one of the parents, and that the trait of the other parent was not
seen in them
The tall and dwarf traits were identical to their parents and did not show any
blending, of the character.
Mathematically he calculated that in F2 generation:
 ¼ tall plants were with genotype TT while
 1/2 were Tt and
 ¼ were tt.
But Tt and TT were tall, so phenotypically ¾ of the plants were tall while the
only ¼ of them were phenotypically and genotypically dwarf.
The phenotypic ratio was calculated to be 3 : 1.
The genotypic ratio was calculated to be (TT : Tt : tt), 1 : 2 : 1.

He expressed his observations with the help of Punnett Square.

The Punnett Square:
 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 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 symbols male and female are used to denote the female (eggs) and male
(pollen) of the F1 generation, respectively.
 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 genopytic 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.
Mendel’s conclusions and Laws of Inheritance:
Based on these observations, Mendel proposed that something was being stably
passed down, unchanged, from parent to offspring through the gametes, over
successive generations.
He called these things as ‘factors’.
Now we call them as genes. Genes, therefore, are the units of inheritance.
They contain the information that is required to express a particular trait in an
organism.
Genes which code for a pair of contrasting traits are known as Alleles, i.e., they are
slightly different forms of the same gene.
Allele: A pair of contrasting genes of a trait present on the same loci of
homologous chromosomes is called an allele.
The pair of alleles for height would be TT, Tt or tt.
Alleles can be similar as in the case of homozygotes TT and tt or can be dissimilar
as in the case of the heterozygote Tt.
Mendel also proposed that in a true breeding, tall or dwarf pea variety the allelic
pair of genes for height are identical or homozygous, TT and tt, respectively.
TT and tt are called the genotype of the plant while the descriptive terms tall and
dwarf are the 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 and hence is called the dominant factor while the other factor
is recessive.
In this case T (for tallness) is dominant over t (for dwarf-ness), is recessive.

The Tt plant is heterozygous for genes controlling one character (height), it is a

monohybrid and the cross between TT and tt is a monohybrid cross
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
Mendel’s Findings
 F1 resembles only one parent.
 F2 generation obtained by self-pollination Dominant and recessive forms
appear in a 3 : 1 ratio (phenotypically).
 F2 generation obtained after self-pollination gave genotypic ratio as 1: 2 : 1
ratio of pure and hybrid forms.

Based on his observations on monohybrid crosses Mendel proposed two general

rules to consolidate his understanding of inheritance in monohybrid crosses.
Today these rules are called the Principles or Laws of Inheritance: the First Law
or Law of Dominance and the Second Law or Law of Segregation.
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 F2 . It also explains the
proportion of 3:1 obtained at the F2 .
If a cross is conducted between two characters of parents then the character that
appears in F1 generation is called dominant and the suppressed one which
appears in F2 generation is called recessive.
What exactly is dominance? Why are some alleles dominant and some recessive?

Every gene 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, which modifies the
information that particular allele contains.

Explaination of Dominance:
A pair of alleles is present in a gene and in a diploid organism during gamete
formation the two alleles segregate out.
The two alleles present may be identical(homozygous) or not identical
(hetezygous).

Incomplete Dominance
When experiments on peas were repeated using other traits, 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
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 to 1:2:1. 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) .
 Incomplete dominance results from a cross in which each
parental contribution is genetically unique and gives rise to
progeny whose phenotype is intermediate. Incomplete
dominance is also referred to as semi-dominance and partial
dominance.
Incomplete dominance, also called partial dominance, semi-
dominance, or intermediate inheritance, involves the
formation of third phenotypic traits due to the combination
of parents’ alleles.
 The incomplete dominance concerns the production of
heterozygotes that possess intermediate traits between the two
homozygous traits. These heterozygous organisms have
phenotypes that are a blend of the phenotypes of their
homozygous traits.
 The trait developed is neither dominant nor recessive. Therefore,
none of the alleles from the paired ones are expressed over the
other for a specific trait.
 The dilution of the dominant allele with respect to the recessive
allele is also termed incomplete dominance. There is a reduced
ratio of dominant alleles.
 The variation of an organism’s traits or properties is largely
influenced by incomplete dominance.

The geneticists employ Punnett square to comprehend the

mechanism of incomplete dominance. This facilitates anticipation of
the genotype of the possible progenies.
Two red alleles that are dominant in the homozygous red flower are
denoted by RR. Likewise, rr stands for the homozygous white flower.
The above figure illustrates a test cross performed between Red and
White flower-bearing plants that produce Pink flowers on the
progeny.
The Punnet square demonstrates that heterozygous offspring with
the intermediate characteristic of Pink hue is produced in the first
filial generation or F1 such that no allele predominates over the
others.
Their phenotype is intermediate between the two alleles instead of
being manifested in a fashion that would obscure the potential
 effects of the other allele. All of their heterozygous Rr progeny have
pink blooms.
For F2 generation, when these heterozygotes are cross-pollinated to
observe their corresponding traits,
their offspring will be RR, Rr, and rr in the ratio 1:2:1, i.e., some
inherit two R alleles in some instances, two r alleles in others, and
both R and r in certain cases. This ratio is equivalent to the
Mendelian genotypic ratio.
This clarifies that partial dominance does not necessarily mean
absolute blending since half of the F2 progenies still
demonstrated the parental homozygous alleles, although all of the
offspring in the F1 generation were determined to be heterozygous
with the third phenotype.

Incomplete dominance occurs not only in plants but in animals and

humans. Below, several instances are given to have a deeper look at
the incidence of this genetic event.
Incomplete dominance in plants
 Incomplete dominance was recorded for the first time in Carnation
plants. German scientist Kolreuter crossed true breeding red and
 white carnation flowers that resulted in offspring with pink
phenotypic flowers.
 Red and white flowers of four o’clock plants breed to produce pink
flowered progenies where neither allele was fully dominant.
 Similarly, pink-colored snapdragon flowers produced due to cross-
pollination between red and white snapdragons exemplify
incomplete dominance.
 The light violet color of eggplants is another example of
incomplete dominance, which results when deep purple eggplants
are combined with white eggplants.
Incomplete dominance in animals
Some of the examples of incomplete dominance in animals
are:
 An Andalusian chicken demonstrates incomplete dominance where
a white feathered male and a black feathered female chicken
breed to produce blue and tinged feathered offspring. This is due
to the dilution of genes that reduce the intensity of the effect of
melanin, thereby lightening the color of feathers in offspring.
 Breeding of long and short-furred rabbits produces rabbits with
varying lengths of fur, usually medium-length furs.
 When a long-tailed dog is crossed with a short-tailed dog, a
medium-sized tail is produced in offspring. This demonstrates
incomplete dominance.
 Likewise, breeding a spotted animal with a non-spotted animal
bears offspring with few spots. This is visible in some animals’
bodies, like dogs, cats, and horses.
Incomplete dominance in humans
This event is particularly rare in humans. However, a few
examples are listed below:
 Crossing of parents with straight and curly hair produces children
with semi-curly or wavy hair.
 Incomplete dominance is also visible in human height patterns. In
contrast to being comparable to either of the parents, children of
parents with varied heights tend to be between the parents’ height
ranges.
 An illustration of partial dominance in humans is Tay Sachs disease
which is an autosomal recessive neurological condition. An
enzymatic imbalance could be attributed to incompletely dominant
genes in the parents of Tay Sachs’ carrier, causing them to
 manufacture only half of the required enzyme- enough for a
normal life.
 Familial hypercholesterolemia (FH) is a condition that exemplifies
incomplete dominance. While liver cells produced by one allele
lack cholesterol receptors, those produced by another do so
normally. Due to incomplete dominance, cells are produced that
lack sufficient receptors to remove harmful cholesterol from the
bloodstream completely.

INCOMPLETE DOMINANCE
The inheritance in which the alleles occupying the same position on
homologous chromosome express themselves partially when present together
in a hybrid is known as incomplete dominance.
The F 1 individuals have the characters intermediates to the characters of the
parents in this type of inheritance.
For example- In Snapdragon (Antirrhinum majus ) a cross between red-flowered
plant and a white-flowered plant produces pink-flowered plants in F 1
generation.
On selfing these F 1 plants give red, pink and white-flowered plants in F 2
generation in the ratio of 1 : 2 : 1
‘R’(red) is incompletely dominant over ‘r’ (white) ratio of 1 : 2 : 1.
In this case, the genotypic ratio is the same i.e., 1 : 2 : 1.

Co-dominance
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 I A , I B and i.
The alleles I A and I B 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.
I A and I B are completely dominant over i, in other words when I A and i are
present only I A expresses (because i does not produce any sugar), and when I B
and i are present I B expresses.
But when I A and I B 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.
How many phenotypes are possible?

MULTIPLE ALLELE AND CODOMINANCE

A set of more than two genes present on the same loci controlling the same
characteristic is known as multiple allelic genes. Example-ABO blood group type
in human beings .‘ABO blood groups are controlled by the gene I.
Sugar polymers protrudes from the surface of plasma membrane of the red
blood cells and The formation of sugar is controlled by the gene. y
The gene I has three alleles I A, IB and i.
I A and I B are completely dominant over i
A’ blood group have ‘A’ type of glycoproteins (a-antigen).
‘B’ type blood group have ‘B’ type glycoprotein (b-antigen)
‘AB’ have both types of antigens whereas ‘O’ group do not have any
glycoproteins on RBC.
Thus, six genotypic combinations are possible with three alleles.
Codominance
In ABO blood group, both I A and I B are dominant over ‘i’.
As the person with genotype I A and I B produces both antigens; the allele I A or
I B are called as codominant and are expressed as AB.
All cases of multiple allelism need not to be codominant.
Allele from Allele from Genotype of Blood
Parent 1 Parent 2 offspring types of
offspring

I A
I A
I AI A A

I A
IB I AI B AB

I A i IAi A

IB I A
I AI B AB

IB IB IBIB B

IB i IBi B
i i ii O

ABO blood grouping also provides a good example of multiple alleles? Here you
can see that there are more than two, i.e., three alleles, governing the same
character. Since in an individual only two alleles can be present, multiple alleles
can be found only when population studies are made.
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.

It states that the alleles remain together but segregate at the time of gamete
formation.
The alleles T and t segregate at the time of gamete formation and when the
gametes fused the recessive trait appeared in F2 generation even when it was
absent in F1 generation.

TEST CROSS AND BACK CROSS

In genetic it is important to find out the genotype of the parent involved in the
cross.
This can be done by back cross or test cross.
A cross where F1 progeny is crossed with either of the parents is called back
cross.
F1 X TT (dominant parent)
F1 X tt (recessive parent)
A cross where the F1 progeny is crossed with recessive parent (homozygous) to
test the homozygosity or heterozygosity of the parent is called test cross.
The progeny in F2 will be produced in the ratio of 1 : 1 (i.e., 50%).
Test cross is used for determining whether the parent plants in the cross are pure
for the traits under study.
 In genetic it is important to find out the genotype of the parent involved in the
cross.
This can be done by back cross or test cross.
Example- ⚪ If we want to determine the genotype of a violet flower pea plant
then it can be crossed with the dominant parent or the recessive parent

All flowers are violet Half the flowers are violet and
Unknown flower is half white
homozygous dominant Unknown flower is
Heterozygous recessive
INHERITANCE OF TWO GENES
Mendel also studied the inheritance of two traits at a time.
Seed shape and Seed color.
Such a cross where inheritance of two traits is studied simultaneously is known as
Dihybrid cross.
 He crossed plants having Round and Yellow seeds with plants having
Wrinkled and green seeds.
 The plant with Round and yellow seed was represented by RRYY and
 The one with Wrinkled and green seed was represented by rryy.
 The F 1 generation consisted of Round and Yellow seeded plants.
 F 1 generation when self-pollinated lead to the formation F 2 generation.
 Consisting of :
Round yellow (9)
Round green (3)
Wrinkled yellow (3)
Wrinkled green seeded plants (1)
The phenotypic ratio was 9:3:3:1.
Consider the segregation of one pair of genes RRYY and rryy
Fifty per cent of the gametes have the gene R and the other 50 per cent have r
gene.
Segregation of allele Y lead to Fifty percent of the gametes with Y gene while the
other fifty percent had y gene.
The segregation R and r is independent of Y an y gene.
Fifty per cent of the r bearing gametes have Y gene and the other 50 per
cent gametes have y gene and
50 per cent gene of the R bearing gametes have Y gene and the other 50
per cent have y gene.
There are four genotypes of gametes-
 RY,
 Ry,
 rY and
 ry
Each with a frequency of 25 per cent or 1/4th of the total gametes produced

Interpretation of Mendel’s Results

The Principle Law of Segregation or Law of Independent Assortment:
It states that when two or more characters are crossed or combined in a hybrid,
the alleles segregate independently of each other during gamete formation.

Law of Independent Assortment

Based upon his observations on dihybrid cross, Mendel proposed a second set of
generalizations that we call Mendel’s 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’.
Mendel's law of independent assortment states that the alleles of two (or more)
different genes get sorted into gametes independently of one another. In other
words, the allele a gamete receives for one gene does not influence the allele
received for another gene.
The Punnett square can be effectively used to understand the independent
segregation of the two pairs of genes during meiosis and the production of eggs
and pollen in the F1 RrYy plant.
The important thing to remember here is that segregation of 50 per cent R and 50
per cent r is independent from the segregation of 50 per cent Y and 50 per
cent y.
Therefore, 50 per cent of the r bearing gametes has Y and the other 50 per cent
has y. Similarly, 50 per cent of the R bearing gametes has Y and the other 50 per
cent has y.
Thus there are four genotypes of gametes (four types of pollen and four types of
eggs). The four types are RY, Ry, rY and ry each with a frequency of 25 per cent
or 1/4th of the total gametes produced
When you write down the four types of eggs and pollen on the two sides of a
Punnett square it is very easy to derive the composition of the zygotes that give
rise to the F2 plants
This can be regarded as combination of PR of two monohybrid
crosses
(3 Round : 1 Wrinkled) x (3 Yellow : 1 Green) = 9 Round, Yellow :
3 Wrinkled, Yellow: 3 Round, Green : 1 Wrinkled, Green
Chromosomal Theory of Inheritance

Mendel published his work on inheritance of characters in 1865 but for several reasons, it remained
unrecognised till 1900.

Firstly, communication was not easy (as it is now) in those days and his work could not be widely
publicised.

Secondly, his concept of genes (or factors, in Mendel’s words) 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
not accepted by his contemporaries as an explanation for the apparently continuous variation seen in
nature.

Thirdly, Mendel’s approach of using mathematics to explain biological phenomena was totally new and
unacceptable to many of the biologists of his time.

Finally, though Mendel’s work suggested that factors (genes) were discrete units, he could not provide
any physical proof for the existence of factors or say what they were made of.

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.

In 1902, Theodor Boveri (GERMAN) observed that proper embryonic

development of sea urchins does not occur unless chromosomes are present.

That same year, Walter Sutton (AMERICAN) observed the separation of

chromosomes into daughter cells during meiosis.

Together, these observations led to the development of the Chromosomal Theory

of Inheritance, which identified chromosomes as the genetic material responsible
for Mendelian inheritance.
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.

G1 G2 Meiosis I Germ Cells

Meiosis and germ cell formation in a cell with four chromosomes.

Possibility I Possibility II One long orange and short green One long orange and short red chromosome
and long yellow and chromosome and long yellow and short red chromosome at the short green
chromosome at the same pole
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.

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.
CHROMOSOMAL THEORY OF INHERITANCE
Walter Sutton and Theodore Boveri noted that the behavior of chromosomes was
parallel to the behavior of genes and used chromosome movement to explain
Mendel’s laws.
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.
The chromosomes segregate at the time of gamete formation and along with
them the alleles present on the chromosomes also segregate out .
Both the chromosomes and alleles occur in pairs One pair of chromosomes
segregate independently of another pair.
While in genes independent pairs segregate independently of each other.
During gamete formation in meiosis I, during Anaphase the two chromosome
pairs align at the metaphase plate independently of each other.
Each gamete has only one allele of each gene present in the chromosome.
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)

while others were loosely linked (showed higher recombination).

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 Project, described later

LINKAGE AND RECOMBINATION

T.H. Morgan conducted experiments with Drosophila (fruit fly) to show that genes
are located on chromosomes.
He selected Drosophila melanogaster for his experiments due to following
reasons:
  Life cycle is short of Drosophila. They complete their life cycle in about two
weeks,
 A large number of progenies may be produced in one mating only.
 Easy laboratory conditions are sufficient for experiment. They could be
grown on simple synthetic medium in the laboratory.
 Each cell of Drosophila consists of only four pairs of chromosomes. They all
are different in size.
 Out of four pairs, three are Autosomes and similar in males and females.
The fourth pair is Allosome or Sex chromosome.
 There was a clear differentiation of the sexes – the male and female flies
are easily distinguishable.
 It has many types of hereditary variations that can be that can be seen with
low power microscopes.

T.H. Morgan conducted following experiments (crosses) on Drosophila (normally

red-eyed).
Cross A-
He crossed Yellow- bodied and white eyed female with brown –bodied and red
eyed male.
The F1 progeny was intercrossed.
The result did not follow the mendelian ratio of a dihybrid cross i.e 9:3:3:1.
The parental combination were 98.7% and recombinats were 1.3%.
He again conducted across between crossed white-bodied female having
miniature wings with yellow-bodied male with normal wings(wild type).
The parental combination were 62.8% while the recombinants were 37.2%.
Morgan knew that the genes were located on the X chromosome and understood
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.
He described such an association between two genes that expresses more of the
parental characteristics as linkage.
Thus he concluded from the two crosses that to genes body colour and wings size
are loosly linked and thus, more crossing over and more number of recombinants.

Linkage and Crossing Over Linkage

The tendency of genes present on a chromosome to inherit together in the next
generation is known as linkage.
Types of linkage-
 Complete linkage
 Incomplete linkage

1. Complete Linkage
In this process, two or more genes on a chromosome are close to each other and
inherit together in the next generation. In this process, there is no crossing over
between the genes
2. Incomplete Linkage
In this process, the genes are not too close to each other and a little crossing over
takes place between the genes.They segregate and are inherited independently,
and thus, a new type of combinations are produced in the successive generation

Linkage Group and Linkage Map

Linkage group
The group of linked genes inherited together in the progeny is called linkage
group.
Each linkage group is related to a particular chromosome.
In Drosophila, there are 4 pairs of chromosomes, so, 4 linkage groups,
in man, there are 23 linkage groups.
Linkage map
The frequency of crossing over between the two genes is directly proportional to
the relative distance between them.
Morgan and Sturtevant proposed
“let 1% crossing over (recombination) be equal to 1 map unit”.
Alfred Sturtevant used the frequency of recombination between gene pairs on the
same chromosome as a measure of the distance between genes and he also
mapped their position on the chromosome.
Genetic maps have been used in the sequence of DNA in Human Genome Project

PLEIOTROPY

There are instances where a single gene can exhibit multiple phenotypic expression. Such a gene is
called a pleiotropic gene.

The underlying mechanism of pleiotropy in most cases is the effect of a gene on metabolic pathways
which contribute towards different phenotypes.

An example of this is the disease phenylketonuria, which occurs in humans.

The disease is caused by mutation in the gene that codes for the enzyme phenyl alanine hydroxylase
(single gene mutation).

This manifests itself through phenotypic expression characterised by mental retardation and a reduction
in hair and skin pigmentation.

EXCEPTION TO MENDELIAN PRINCIPLES

Gene Interaction can be of two types

Intragenic Interaction

Intergenic Interaction

Intragenic Interaction-Two alleles of a gene present on the same locus of the homologous

chromosome produce modified phenotype.

It is of the following type-

Incomplete dominance

Multiple Allelism

Coodominace

Intergenic Interaction-The genes are present on different chromosomes and produce a changed
phenotypic effect.

It includes-

Epistatic gene

Dupliacte gene

Complementary gene

Supplementary gene

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 which 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.

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

Thus we have 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.
Sex Determination in Humans

It has already been mentioned that the sex determining mechanism in case of humans is XY type.

Out of 23 pairs of chromosomes present, 22 pairs are exactly same in both males and females; these are
the autosomes.

A pair of X-chromosomes are present in the female, whereas the presence of an X and Y chromosome
are determinant of the male characteristic.

During spermatogenesis among males, two types of gametes are produced.

50 per cent of the total sperm produced carry the X-chromosome and the rest 50 per cent has Y-
chromosome besides the autosomes.

Females, however, produce only one type of ovum with an X-chromosome.

There is an equal probability of fertilisation of the ovum with the sperm carrying either X or Y
chromosome.

In case the ovum fertilises with a sperm carrying X-chromosome the zygote develops into a female (XX)
and the fertilisation of ovum with Y-chromosome carrying sperm results into a male offspring.

Thus, it is evident that it is the genetic makeup of the sperm that determines the sex of the child.

It is also evident that in each pregnancy there is always 50 per cent probability of either a male or a
female child.

SEX DETERMINATION
Establishment of sex of the individual through different ways is known as sex
determination.
In some animals like turtle it is determined by the temperature i.e the incubation
temperature. In Bonnelia the larvae do not have any sex. The larva which grows in
the mud matures into female while the larva that develops near the proboscis of
female develops into male.

While in Drosophila ,humans, grasshopper ,birds sex ids determined genetically.

The studies on some insects lead to the understanding of genetic/chromosomal

mechanism of sex determination.
Henking found a nuclear structure during spermatogenesis of a few insects.
He also found out that 50 per cent of the sperm received this structure after
spermatogenesis while the other 50 per cent sperm did not receive it.
He called the structure as the X body but he could not explain its importance.
Later some scientists found out that the ‘X body’ was in fact a chromosome of sex
determination and was named X chromosome.
Autosomes and Allosomes
The chromosomes other than sex chromosomes in body cells (diploid) are called
autosomes.
The sex chromosomes which are morphologically different and are associated
with sex determination are called allosomes or Sex chromosomes e.g. X and Y

Heterogametic and Homogametic Organisms

The individual having two morphologically different sex chromosomes and
producing two types of gametes is called heterogametic (XY).
The individual having two morphologically similar sex chromosomes and
producing all gametes of the same type is known as homogametic (XX).
XY Type
In Drosophila and mammals the males have XY sex chromosome while the female
have XX sex chromosome.
The males are heterogametic as half their gametes have X and the other half have
Y sex chromosomes. The female is homogametic as all her gametes contain only
one X sex chromosome.

Sex Determination in Humans

Humans have 23 pairs of chromosome.Out of which 22 pairs are autosomes and
the 23rd pair is the sex chromosome.
During spermatogenesis, half the gametes in male have X sex chromosome i.e
22+X while the other half gametes have Y sex chromosome i.e 22 +Y.
The female during oogenesis produce ova that always will have X sex
chromosome.
Thus the gametes will be 22+X.
Eggs fertilised by sperm having 22+X chromosomes become females while those
fertilised by sperms that have 22+Y chromosome become males.
It is the genetic makeup of the sperm that determines the sex of the child.
During pregnancy there is always 50 per cent probability of either a male or a
female child.

“XO” Type
This type of sex determination is found in certain insects and roundworms. It is
produced due to non-disjunction of chromosomes during meiosis and then the egg
is fertilised by a sperm lacking X-chromosome (Male having only one X
chromosome i.e., XO and the female having two X-chromosomes).

“ZW” Type
In birds, 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. The female is
heterogametic as half the gametes produced have Z sex chromosome and half the
gametes have W sex chromosome. The male is homogametic as all the gamertes
have only Z sex chromosme.
Chromosomal Theory Of Inheritance:
From 1879-1892, Flemming, Strasburger, Waldeyer, van Beneden, and Weismann
made significant contributions to our concepts of chromosomes.
Flemming (1882) observed structures in the nucleus of salamanders that bound
dye, and these structures had a string like appearance. He termed the structures
chromatin (or colored substance).
He also developed the concept of cell division that he later termed mitosis.
The universality of this discovery is attributed to Strasburger who discovered the
same process in plants.
Waldeyer, in 1888, called the structures that divided during mitosis chromosomes
(or colored bodies).
Weismann made the very critical observation that sperm and egg cells contain
exactly half the number of chromosomes.
van Beneden further observed that when a sperm cell fertilizes an egg, the result
is the diploid chromosome number found in cells that undergo mitosis.
He also determined that the sperm and egg cell each contribute equal numbers of
chromosomes to the zygote.
This final result demonstrated a link between chromosome and inheritance
because it was generally known that offspring receive traits from both of their
parents.
These concepts were echoed by Hugo deVries (1889) but from a different
perspective.
He had called the hereditary material pangenes. He felt the pangene was larger
than a single chemical molecule, yet still invisible.
All of the pangenes that controlled all of the organisms traits were found within
the cell of a diploid organism.
He further suggested that reproductive cells receive half of the pangenes and
that when reproductive cells unite the diploid number of pangenes is restored.

Later E.B. Wilson released his book The Cell in Development and Inheritance.
His book also discussed the relationship between chromosomes and heredity.
Although the relationship was suggested, the linkage was most strongly
demonstrated by Sutton and Boveri.
Walter Sutton (USA) and Theodor Boveri (German) worked independently.
Boveri observed (as had van Beneden) that male and female gametes contribute
an equal number of chromosomes to the zygote.
In 1902, he made the link between chromosomes and the factors that were
described by Mendel. He said "… the characters dealt with in Mendelian
experiments are truly connected to specific chromosomes."
Sutton described chromosomes as unique individual units that occur in pairs that
separate during meiosis.
These concepts of Boveri and Sutton are known as the Chromosomal Theory of
Inheritance. These studies set the stage for the intense study of chromosomes
and their role in heredity.
The final link between heredity and chromosomes required definitive proof that a
genetic factor was indeed located on a chromosome.
The work of Thomas Hunt Morgan, and later Calvin Bridges, provided such proof.
Morgan, in 1910, discovered a mutant line of Drosophila with white rather than
the wild type red eye.
He suggested by genetic experiments that the gene for eye color was located on
the X chromosome.
This is one of the two sex chromosomes in the fly.
Bridges followed this up by cytological experiments in 1914 that coupled the
presence of the X chromosome with a specific eye color. This demonstrated
conclusively that genes indeed reside on chromosomes.
If chromosomes were the carriers of genetic information, then they must contain
all of the factors that make an organism unique.
Yet, the total number of chromosomes is vastly less than the number of traits. For
chromosomes to actually contain the genetic material, they must be shown to
contain many factors.
This was conclusively shown by researchers in Morgan’s laboratory.
By mating among Drosophila, it was shown that a chromosome contains multiple
genes that could be organized into a linear linkage group.
The discovery that the number of linkage groups that could be mapped in a
species was equal to the number of chromosomes solidified the importance of
chromosomes in heredity.
It was clear that genes resided on chromosomes, and chromosomes were the
functional unit of heredity.
Alfred Sturtevant (1925) demonstrated that the actual physical order of the genes
was also essential.
He discovered the concept of position effect by showing that altering the physical
environment of a gene on a chromosome altered its function.
This implied that the actual physical organization of the chromosome was
essential for proper phenotypic expression.
Therefore, it became clear that we could not simply look at a single gene to
understand its expression, but rather we needed to consider the entire
chromosomal region.
In many regards, this pointed the way to genomics, a science where we
considered the entire DNA complement.

The Chromosomal Theory of Inheritance was consistent with Mendel’s laws and
was supported by the following observations:

 During meiosis, homologous chromosome pairs migrate as discrete

structures that are independent of other chromosome pairs.
 The sorting of chromosomes from each homologous pair into pre-gametes
appears to be random.
 Each parent synthesizes gametes that contain only half of their
chromosomal complement.
 Even though male and female gametes (sperm and egg) differ in size and
morphology, they have the same number of chromosomes, suggesting
equal genetic contributions from each parent.
 The gametic chromosomes combine during fertilization to produce offspring
with the same chromosome number as their parents.