CHAPTER 5

PRINCIPLES OF INHERITANCE
AND VARIATION
Introduction –
• Elephant always gives birth only to a baby elephant and not some other
animal, pea seed forms only a pea plant and not any other plant, siblings
sometimes look so similar to each other or sometimes even so different.
• All the above happen due to inheritance of genes or characters from
parents to their offerings.
• Inheritance and variations are studied in a branch of biology known as
Genetics.
• Genetics –
• Genetics deals with the inheritance, as well as the variation of characters
from parents to offspring.
• Term genetics was coined by Bateson.
• Father of modern genetics is Gregor John Mendel.
• Father of experimental genetics is T.H Morgon.
• Inheritance –
• Inheritance is the process by which characters are passed on from
parent to progeny; it is the basis of heredity.
• Variation –
• Variation is the degree by which progeny differ from their parents.
• Variations among the organisms are the result of crossing over (genetic
recombination), mutation and due to fusion of male and female gametes.
• Variations are classified into following types.
• Somatic variation –
• These variations influence somatic body cells.
• These variations appeared after the birth and non-genetically.
• It cannot inherit from one generation to next generation (non inheritable).
• Germinal variation –
• It happens in germ cells and is inheritable.
• It is further two types
• Continuous variation –
• It happens due to crossing over or recombination during gametes
formation.
• Discontinuous variation –
• It happens due to mutation.
 • Note: Variation is very important in speciation (new species formation).
• Humans knew from as early as 8000-1000 B.C. that one of the causes of
variation was hidden in sexual reproduction.
• In ancient times people carried out breeding among the wild plants and
animals and artificially selected (artificial selection) new progeny which was
having desire characters.
• Thus They exploited the variations that were naturally present in the wild
populations of plants and animals by breeding and artificial selection.
• For example, through artificial selection and domestication from
ancestral wild cows, we have well-known Indian breeds, e.g., Sahiwal
cows in Punjab.
• After seeing the above attempts our ancestors for exploitation of variations
we can say our ancestors were well aware about the inheritance of
characters and variation but they had very little idea about the scientific
basis of these phenomena.
1.1 Mendel’s laws of inheritance –
• It was during the mid-nineteenth century that headway (service) was made
in the understanding of inheritance.
• Gregor Mendel, conducted hybridisation experiments (plant breeding)
on garden peas.
• Mendel borne in Austria in 1822.
• He conducted plant hybridization experiment for seven years (1856-
1863) and proposed the laws of inheritance in living organisms.
• During Mendel’s investigations into inheritance patterns it was for the
first time that statistical analysis and mathematical logic were applied to
problems in biology.
1.1.1 Reasons for selection of pea plants for hybridization programs –
• Mendel selected pea plants for his hybridization programs for following
reasons –
• It was annual plants and was having short life span.
• Plants were having bisexual flowers.
• The flowers were predominantly self-pollinating because of bisexual
nature.
• It is easy to get pure lines for several generations.
1.1.2 Selection of true breeding (pure lines) plants –
• Mendel investigated characters in the garden pea plant that were
manifested as two opposing traits, e.g., tall or dwarf plants, yellow or
green seeds.
• Mendel conducted such artificial pollination/cross pollination/
experiments/artificial hybridization using several true-breeding pea lines.
• 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, as pairs which were
similar except for one character with contrasting traits.
• Some of the contrasting traits selected were smooth or wrinkled seeds,
yellow or green seeds, inflated (full) or constricted green or yellow pods
and tall or dwarf plants.

Figure: Seven pairs of contrasting traits in pea plant studied by Mendel

 • His experiments had a large sampling size, which gave greater credibility
to the data that he collected.
• Also, 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.
• This allowed him to set up a basic framework of rules governing
inheritance, which was expanded on by later scientists to account for all
the diverse natural observations and the complexity inherent in them.
• Note: All the 7 pairs of mendelian characters are found on 4
chromosomes (1, 4, 5, 7).
1.2 Inheritance of Single gene –
1.2.1 Mendel hybridization experiment –
• Mendel crossed (hybridization) tall and dwarf pea plants to study the
inheritance of one gene.
• Settled seeds were collected and the seeds were germinated to generate
plants of the first hybrid generation.
• This generation is also called the Filial1 progeny or the F1 progeny.
• Mendel observed that all the F1 progeny plants were tall and were
character of parent like tall and none were dwarf like dwarf parent.
• Mendel made similar experiment for the other pairs of 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.

Figure: Steps in making a cross in pea

 1.2.2 Self-pollination of F1 generation or monohybrid cross –
• Mendel then self-pollinated the tall F1 hybrid plants and to his surprise
found that in the Filial2 (F2) generation some of the progeny were
‘dwarf.
• The dwarf character was not seen in the F1 generation but found in F2
generation.
• The proportion of tall and dwarf plant was 3:1. 3/4 plants were tall while
1/4th plants of the F2 generation were dwarf.
• The tall and dwarf traits were identical to their parental type and did not
show any blending (mixing).
• All the offspring were either tall or dwarf, none were of intermediate
height.
• Same results were obtained when Mendel did same experiment with other
traits also.
1.2.3 Mendel’s observations –
• In Mendel experiment only one of the parental traits was expressed in the F1
generation while at the F2 stage both the traits were expressed in the
proportion 3:1.
• The contrasting traits (opposite traits like tall & dwarf) did not show any
blending at either F1 or F2 stage.
• Based on the above observations, Mendel proposed that something was
being stably transferred, unchanged, from parents to offspring through
the gametes, over successive generations.
• He called these things as ‘factors’. Now factors are called genes.
• Genes, therefore, are the basic units of inheritance.
• They contain the information that is required to express a particular
trait in an organism.
• Alleles –
• Genes which code for a pair of contrasting traits are known as alleles.
• Alleles are different forms of the same gene.
• If we use alphabetical symbols for each gene, then the capital letter is used
for the trait expressed at (Tall) the F1 stage and the small alphabet (t) for
the other trait.
• For example, in case of the character of height, T is used for the Tall trait
and t for the ‘dwarf’, and T and t are alleles of each other for a gene of
height.
• Hence, in plants the pair of alleles for height would be TT, Tt or 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 and for heterozygous condition it is Tt.

Figure: Diagrammatic representation of monohybrid cross

• TT and tt are called the genotype of the plant while the descriptive terms
tall and dwarf are the phenotype.
• What then would be the phenotype of a plant that had a genotype Tt? 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.
• It is convenient (and logical) to use the capital and lower case of an
alphabetical symbol to remember this concept of dominance and
recessiveness.
• (Do not use T for tall and d for dwarf because you will find it difficult to
remember whether T and d are alleles of the same gene/character or not).
• 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.
• Since 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.
• 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.
• In this way the gametes of the tall TT plants have the allele T and the
gametes of the dwarf tt plants have the allele t.
• During fertilisation the two alleles, T from one parent say, through the
pollen, and t from the other parent, then through the egg, are united to
produce zygotes that have one T allele and one t allele.
• In other words the hybrids have Tt. Since these hybrids contain alleles
which express contrasting traits, the plants are heterozygous.
• 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 symbols & and %
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.
• The 1/4 : 1/2 : 1/4 ratio of TT: Tt: tt is mathematically condensable to the
form of the binomial expression (ax +by)2, that has the gametes bearing
genes T or t in equal frequency of ½.
• The expression is expanded as given below : (1/2T + 1/2 t)2 = (1/2T + 1/2t)
X (1/2T + 1/2t) = 1/4 TT + 1/2Tt + 1/4 tt Mendel self-pollinated the F2
plants and found that dwarf F2 plants continued to generate dwarf plants in
F3 and F4 generations.
• He concluded that the genotype of the dwarfs was homozygous – tt. What do
you think he would have got had he self-pollinated a tall F2 plant? From the
preceeding paragraphs it is clear that though the genotypic ratios can be
calculated using mathematical probability, by simply looking at the
 phenotype of a dominant trait, it is not possible to know the genotypic
composition.
• That is, for example, whether a tall plant from F1 or F2 has TT or Tt
composition cannot be predicted.
1.2.4 Test cross –
• To determine the genotype of a tall plant at F2, Mendel crossed the tall
plant from F2 with a dwarf plant. This he called a test cross.
• A test cross always shows two types of offsprings (50% dominant character
& 50 % recessive character)
• In a typical test cross an organism (pea plants here) showing a dominant
phenotype (and whose genotype is to be determined) is crossed with the
recessive parent instead of self-crossing.
• The progenies of such a cross can easily be analysed to predict the
genotype of the test organism.
• Figure 5.5 shows the results of typical test cross where violet colour flower
(W) is dominant over white colour flower (w).
• A test cross always shows two types of offsprings (50% dominant character
& 50 % recessive character).
• 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.
1.3 Law of Dominance –
• 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.
1.4 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.
1.4.1 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.) and Mirabilis jalapa (4 O Clock plant) are 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 of
• 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.
• (ii) A non-functional enzyme.
• (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 affected.
• 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.
1.4.2 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. 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.

• How many phenotypes are possible? Table 5.2: Table Showing the Genetic
Basis of Blood Groups Do you realise that the example of 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.
• Note: In human ABO blood grouping there are 6 genotypes and 4
phenotypes.
• Human ABO blood grouping is the example of multiple allelism because all
the four types of blood group developed by random combination of
three types alleles (A, B & i).
1.4.3 Pleiotropy –
• We have so far seen the effect of a gene on a single phenotype or trait.
There are however instances where a single gene can exhibit multiple
phenotypic expression. Such a gene is called a pleiotropic gene and
phenomenon known as pleiotropy.
• 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.
• Another example of pleiotropy is starch synthesis in pea seeds is
controlled by one gene.
• It has two alleles (B and b). Starch is synthesized 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
(because of incomplete dominance).
• 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.
1.5 Inheritance of two genes –
• 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.
• Here can you tell which of the characters in the pairs yellow/ green colour
and round/wrinkled shape was dominant?
• 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 as in showing the
genotypes of the parent plants.
• The gametes RY and ry unite on fertilisation to produce the F1 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.

1.5.1 Law of Independent Assortment –

• In the dihybrid cross (Figure 5.7), the phenotypes round, yellow; wrinkled,
yellow; round, green and wrinkled, green appeared in the ratio 9:3:3:1.
Such a ratio was observed for several pairs of characters that Mendel
studied.
• The ratio of 9:3:3:1 can be derived as a combination series of 3 yellow: 1
green, with 3 round : 1 wrinkled. This derivation can be written as follows:
 (3 Round : 1 Wrinkled) (3 Yellow : 1 Green) = 9 Round, Yellow : 3
Wrinkled, Yellow: 3 Round, Green : 1 Wrinkled, Green
• Based upon such observations on dihybrid crosses (crosses between plants
differing in two traits) 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’.
• 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.
• Consider the segregation of one pair of genes R and r. Fifty per cent of the
gametes have the gene R and the other 50 per cent have r.
• Now besides each gamete having either R or r, it should also have the allele
Y or y.
• 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 (Figure 5.7).
• Although there are 16 squares how many different types of genotypes and
phenotypes are formed? Note them down in the format given.
• Can you, using the Punnett square data work out the genotypic ratio at the
F2 stage and fill in the format given? Is the genotypic ratio also 9:3:3:1?
1.5.2 Multiple factor (polygenic) inheritance –
• If any character develops by multiple genes or factors called polygenic
character and their inheritance called polygenic inheritance e.g. Human
height and human skin colour.
• Note: Human skin color is regulated by three genes. If all the three genes
have dominant alleles (AABBCC) then person skin will be dark (Negro), If
all alleles are recessive (aabbcc) then skin color will be white while if
 heterozygous condition (AaBbCc) is there then skin color will be
intermediate (Mullato).
1.5.3 Reasons for unrecognition of mendel’s work –
• Mendel published his work on inheritance of characters in 1865 but for
several reasons, it remained unrecognized till 1900.
• There are several reasons for unrecognition of mendel work.
• i) Firstly, communication was not easy (as it is now) in those days and his
work could not be widely publicized.
• ii) 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.
• iii) Thirdly, Mendel’s approach of using mathematics to explain
biological phenomena was totally new and unacceptable to many of the
biologists of his time.
• iv) 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.
1.5.4 Rediscovery of Mendel’s work –
• 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).
1.6 Chromosomal theory of inheritance –
• By 1902, the chromosome movement during meiosis had been worked out.
• 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.
• Recall that you have studied the behavior 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.

Figure: Meiosis and germ cell formation in a cell with four chromosomes. Can you see
how chromosomes segregate when germ cells
are formed?
• 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 color 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.
• Note: Chromosomal theory stated that chromosomes are linear structure
on which genes are present on specific sites called Loci.
1.6.1 Experimental verification of chromosomal theory of T.H Morgan –
• 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.
1.6.1.1 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).

Figure: (a) Male Drosophila (b) Female Drosophila

• Morgan and his group knew that the genes were located on the X
chromosome (Section 5.4) 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) (Figure 5.11, Cross A) while others were loosely
linked (showed higher recombination) (Figure 5.11, 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.
1.6.1.2 Genetic mapping –
• The distance between two genes on chromosome called Map unit.
• 1 map unit is equal to 1 % recombination. For example two genes that
recombined with a frequency of 3.5 % are said to be located 3.5 map
units apart.
• Unit of map unit is centimorgon.
1.7 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. Do you think the number of chromosomes in the male and female are
equal?

• 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.
1.7.1 Sex determination in Grasshopper (XX & X0 type) –
• 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.
1.7.2 Sex determination in Drosophila and in humans (XX & XY type) –
• 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
counterpart 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.
• (b) Some gametes with X-chromosome and some with Y-chromosome.
• Such types of sex determination mechanism are designated to be the
example of male heterogamety.
1.7.3 Sex determination in birds –
• 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.
1.7.5 Sex Determination in Honey Bee –
• The sex determination in honey bee is based on the number of sets of
chromosomes an individual receives.
• An offspring formed from the union of a sperm and an egg develops as a
female (diploid queen or worker), and an unfertilized egg develops as a
male (haploid drone) by means of parthenogenesis.
• This means that the males have half the number of chromosomes than
that of a female.
• The females are diploid having 32 chromosomes and males are haploid,
i.e., having 16 chromosomes.
• This is called as haplodiploid sex-determination system and has special
characteristic features such as the males produce sperms by mitosis they
do not have father and thus cannot have sons, but have a grandfather and
can have grandsons.
1.7.6 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 is 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.
• It is unfortunate that in our society women are blamed for giving birth
to female children and have been ostracised and ill-treated because of this
false notion. How is the sex-determination mechanism different in the birds?
Is the sperm or the egg responsible for the sex of the chicks?
1.8 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.
1.8.1 Mutagens –
• There are many chemical and physical factors that induce mutations. These
are referred to as mutagens.
• UV radiations can cause mutations in organisms.
• Point mutation –
• 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.
 • a) Insertion – In this type extra base pairs are added in in DNA.
• b) Deletion – In this type loss of base pairs take place from DNA.
• Frame-shift mutation – Deletions and insertions of base pairs of DNA,
causes change of whole frame of DNA called frame-shift mutations.
• Substitution mutation –
• In this type substitution of one base takes place by other base called
substitution mutation e.g. GAG into GUG in sickle cell anaemia.
• Transition & Transversion – In point mutation if purine replaced by
purine called transition while when purine replaced by pyrimidine called
transversion mutation.
1.9 Genetic disorders –
1.9.1 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 analyzing
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 in.
• 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.

Figure: Symbols used in the human pedigree analysis

1.9.2 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 Figure 5.14 for dominant and
recessive traits.
1.9.2.1 Autosomal recessive disorder –
• There are several types of autosomal recessive disorders which are given
below.
• i) Sickle-cell anemia –
• 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
(HbS HbS) 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.

Figure Micrograph of the red blood cells and the amino acid composition of the
relevant portion of  chain of haemoglobin: (a) From a normal individual; (b) From
an individual with sickle-cell anaemia.
• ii) 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.

(a) Autosomal dominant trait (b) Autosomal Recessive Trait

e.g. Myotonic dystrophy e.g. Sickel-cell anaemia
• iii) Thalassemia –
• This is also an autosome-linked recessive blood disease transmitted from
parents to the offspring when both the partners are unaffected carrier for the
gene (or heterozygous).
• The defect could be due to either mutation or deletion which ultimately
results in reduced rate of synthesis of one of the globin chains (A and B
chains) that make up haemoglobin.
• This causes the formation of abnormal haemoglobin molecules resulting
into anaemia which is characteristic of the disease.
• Thalassemia can be classified according to which chain of the
haemoglobin molecule is affected.
• A (Alpha) Thalassemia –
• In A Thalassemia, production of Alpha globin chain is affected.
• A Thalassemia is controlled by two closely linked genes HBA1 and
HBA2 on chromosome 16 of each parent and it is observed due to
mutation or deletion of one or more of the four genes.
• The more genes affected, the less alpha globin molecules produced.
• B (Beta) Thalassemia –
• B Thalassemia, production of beta globin chain is affected.
• B Thalassemia is controlled by a single gene HBB on chromosome 11 of
each parent and occurs due to mutation of one or both the genes.
• B Thalassemia, production of Beta globin chain is affected.
• Thalassemia differs from sickle-cell anaemia in that the former is a
quantitative problem of synthesising too few globin molecules while the
latter is a qualitative problem of synthesising an incorrectly functioning
globin.
1.9.2.2 X linked recessive disorder –
• i) 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.
• Haemophilia A is due to deficiency of clotting factor VIII.
• Haemophilia B (also called Christmas disease) is due to deficiency of
clotting factor IX.
• ii) Color blindness –
• It is a sex-linked recessive disorder due to defect in either red or green
cone of eye resulting in failure to discriminate between red and green
colour.
• This defect is due to mutation in certain genes present in the X
chromosome.
• It occurs in about 8 per cent of males and only about 0.4 per cent of
females.
• This is because the genes that lead tored-green colour blindness are on the
X chromosome.
• Males have only one X chromosome and females have two.
• The son of a woman who carries the gene has a 50 per cent chance of
being colour blind. The mother is not herself colour blind because the gene
is recessive. That means that its effect is suppressed by her matching
dominant normal gene.
• A daughter will not normally be colour blind, unless her mother is a
carrier and her father is colour blind.
 1.9.2.3 Y link disorder –
• Genes for this disease are linked to Y chromosome e.g. Hypertrichosis,
Ichthyosis hytrix (scaling of skin).
1.9.3 Chromosomal disorders
• The chromosomal disorders on the other hand are caused due to absence
or excess or abnormal arrangement of one or more chromosomes.
• i) Polyploidy –
• 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.
• ii) Aneuploidy –
• Failure of segregation (nondisjunction) of chromatids during cell division
cycle (Anaphase-I) 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.

Figure: A representative figure showing an individual inflicted with Down’s syndrome

and the corresponding chromosomes of the individual
• Similarly, Turner’s syndrome results due to loss of an X chromosome in
human females.
• 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 (2n+1) or monosomy (2n-1) 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.
• a) 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.
• b) 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.
• c) 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 besides other features
including lack of other secondary sexual characters.
 Important terminologies
• Polyploidy – Organisms with more than two sets of chromosomes are
known as polyploidy.
• Autopolyploid – In this there is numerical increase of the same genome
e.g. Autotriploid (AAA), autotetraploid (AAAA).
• Autoalloploidy – In this genome is more than diploid state. Commonly
autoallopolyploids are hexaploids (AAAABB).
• Autosomal recessive disorder – Albinism, Taysach’s, cystic fibrosis, sickle
cells anaemia, PKU, thalasamia.
• X-linked recessive disorder – Color blindness, haemophilia.
• X-linked dominant disorder – Retinitis pigmentosa.
• Sex influenced trait – The traits which are not expressed due to genes but
by sex hormones called sex influenced trait e.g. Low pitched voice, beard,
and moustaches.
• Sex linked trait – Present only in one sex e.g. Beard in male.
• Receprocal cross – It is a pair of crosses between a male of one strain and
a female of another, and vice versa.
• Back cross – It is the cross of F1 hybrid to either of parent called back
cross.
• Gene – It is a unit of genetic information that occupies a specific position
on a chromosome and comes in multiple versions called alleles.
• Hemizygous – If an individual contains or if there is single allele of a gene
called hemizygous. The male individual is always hemizygous for sex
linked genes.
 IMPORTANT POINTS
• Francis Harry Compton Crick completed Ph.D. in 1954 on a thesis entitled
“X-ray Diffraction: Polypeptides and Proteins”.
• The dominant characters are expressed when factors are in heterozygous
condition (Law of Dominance).
• A point mutation is a change of a single base pair in DNA.
• Inheritable mutations can be studied by generating a pedigree of a
family.
• The recessive characters are only expressed in homozygous conditions.
• Sickle cell anemia is also example of pleiotropy.
• Types of gametes from AABbCC will be 2 types. We can calculates types
of gametes by 2n (n= no of heterozygous).
• Phenotype & Genotype term was given by Johannsen.
• Recombination (crossing over) is directly proportional to distance
between two genes.
• Linkage is inversely proportional to distance between two genes.
• The theory of genic balance of sex determination in Drosophila was
given by Morgan.
• The Mendel’s laws were extended in the form of ‘Chromosomal Theory of
Inheritance.
• it was found that Mendel’s law of independent assortment does not hold
true for the genes that were located on the same chromosomes. These
genes were called as ‘linked genes’.
• Inheritable mutations can be studied by generating a pedigree of a family.
• Chromosomal disorders can be easily studied by analysis of Karyotypes.
• Ratio of supplementary factor is 9:3:3:1.
• Ratio of complementary factor is 9:7.
• Ratio of dominant epistasis is 13:3.
• Ratio of recessive epistasis is 9:3:4.
• Ratio of duplicate genes is 15:1.