Block 1 Heredity and Phenotype

UNIT 2

EXTENSION & MODIFICATIONS

OF MENDELIAN GENETIC
ANALYSIS
ANALYSISI

Structure
2.1 Introduction Epistasis

Objectives Supplementary Gene

Interaction
2.2 Dominance
Duplicate Genes
Complete Dominance
(Pseudoalleles)
Incomplete Dominance
2.5 Lethal Alleles
(Blending Inheritance or
Semi/Intermediate 2.6 Pleiotropy
Dominance)
2.7 Sex-Linked Genes
Codominance
2.8 Degrees of Gene
2.3 Multiple Alleles Expression
ABO Blood Type Alleles in Penetrance
Humans
Expressivity
Rh Factor Alleles in Humans
2.9 Summary
Incompatibility in Plants
2.10 Terminal Question
2.4 Gene Interactions and
2.11 Answers
Modified Mendelian Ratios
Complementary Gene
Interaction (9:7 Phenotypic
Ratio)

2.1 INTRODUCTION
In the previous unit you have been introduced to the concept of genetics and
as to how it has developed unto full fledged discipline of genetics with the
46 Mendel’s work on garden pea. The secret of inheritance mechanism of all the
Unit 2 Extension & Modifications of Mendelian Genetic Analysis-I
traits or characters in an organism, from parents to off-springs, lies in the
genes. It is now an established fact that the segments of DNA express in a
very well defined manner to produce a trait or character. Each gene has two
alternative forms called alleles, each of which occurs at the same locus in
each homologous chromosome. As you all know, the term ‘allele’ comes from
‘allelomorph’ and refers to the different forms of a gene which affect a
phenotype in an organism. Thus number of allelic forms of a gene may be
many in a population, but since each organism has only one pair of
homologous chromosome of a kind, only two of its variants are present in an
organism.

Various interactions may occur between alleles of same genes or alleles of

different genes, which give rise to different phenotypes, making the inheritance
patterns complex. The phenotypic expression of these characters could not be
explained by Mendel’s laws alone and thus this has opened a whole new
myriad of allelic and non-allelic interactions. This unit explains the deviations
from Mendelian principles, its extensions and modifications that have led to
the occurrence of different phenotypes in a progeny as compared to their
parents. Broadly categorizing, such interactions can be classified as-

1) Intragenic interactions: When the two alleles of same gene interact

with each other and affect a phenotype, it is known as inter-allelic, allelic
gene or intragenic interactions, for examples- incomplete dominance, co-
dominance and multiple alleles.

2) Intergenic interactions: If the alleles of different genes, located on

separate loci, interact with each other and influence a phenotype, it is
known as non-allelic or intergenic interactions. For example-
complementary gene interaction, epistasis, supplementary gene
interaction and duplicate genes.

Objectives
After studying this unit, you should be able to:

define various terms related to intergenic and intragenic interactions,

understand the concepts underlying the modifications of Mendelian

genetics,

analyse the influence of various interactions among alleles and genes

on a phenotype,

distinguish among different allelic and non-allelic gene interactions, and

explain the phenomena of production of new phenotypes.

2.2 DOMINANCE
We have studied in the previous unit that Gregor Mendel's experiments laid
the very basis of the concepts of heredity, however, these studies were
confined to the seven traits of pea plant, the conclusions were also restricted
to the observations obtained thereof. The only relationship established by 47
Block 1 Heredity and Phenotype
Mendel between the factors or alleles of a trait was dominance and
recessiveness. This simplicity of the Mendel’s principles also come from the
fact that the inheritance patterns of the seven traits selected by Mendel were
fortunately all straight forward and showed no complexities. Later when the
study was extended to other traits or organisms, it became evident that the
inheritance patterns are far more complex than the simple genetic pattern
described by Mendel. A variety of new traits and characters were investigated
which were the result of some undefined genic/allelic interactions. Let us
discuss the Mendelian concept of complete dominance and its modifications-
incomplete dominance and co-dominance.

2.2.1 Complete Dominance

Complete dominance, as inferred by Mendel, refers to the type of dominance
in which one allele completely masks the expression of other allele and is
therefore said to be completely dominant. The allele which is masked or
remains unexpressed is called recessive. The genotype of organism exhibiting
complete dominance is heterozygous.A dominant feature of a trait is
represented by allele ‘A’ and its recessive feature by allele ‘a’. The
homozygous condition ‘AA’ is responsible for its prominent phenotype while
‘aa’ gives its contrasting phenotype. When both the alleles appear together in
heterozygous condition (Aa), the expression of ‘a’ is completely masked and
only the phenotype of ‘A’ is visible. In such a case the allele ‘A’ is said to be
completely dominant over allele ‘a’, and thus ‘a’ is said to be recessive.
Phenotypically, dominant characters can be easily recognized because they
are expressed even if one dominant allele is present. Recessive alleles need
to come in pair for expression, therefore, they can be recognized only in
homozygous individuals (aa). Thus the heterozygous individuals, who are the
carriers of recessive allele, are not recognizable on the basis of phenotype,
however, can be identified through test cross. In test cross potential carriers
are crossed with homozygous recessive individuals to know their in genotype
(Fig. 2.1).

The relationship of dominance and recessiveness, as deduced by Mendel, can

be explained by taking example of seed shape in pea plants. The seeds in pea
plant can be of any of the two shapes- round or wrinkled. The allele assigned
to round seed shape is ‘R’ while allele for wrinkled seed shape is ‘r’. If a
monohybrid cross is performed between a plant homozygous for round seeds
(RR) with another plant homozygous for wrinkled seeds (rr), the F1 generation
completely resembles the parents with dominant phenotype i.e. round seeds.
In heterozygous plants ‘Rr’, the round shape of seeds completely masks the
wrinkled phenotype. Thus allele ‘R’ for round shape was said to be dominant
over wrinkled ‘r’.

The dominant- recessive pattern as inferred by Mendel was too

straightforward and does not always exhibit as such. The observable
phenotype may occur due to the influence of different environmental factors or
other genic or intergenic interactions. In case of inheritance of seed shape in
peas, the round and wrinkled phenotypes are acquired due to biosynthesis of
amylopectin, a branched chain component of starch. The biosynthesis of
48 amylopectin occurs by the action of starch-branching enzyme I (SBE-I), and
Unit 2 Extension & Modifications of Mendelian Genetic Analysis-I
the activity of this enzyme affects the amount of amylopectin deposition in
seeds. The presence of amylopectin helps in adequate retention of water so
that while maturation of seeds the shrinkage is uniform and they acquire a
round shape. In homozygous RR seeds gene for SBE-I enzyme at ‘r’ locus
was found to be fully functional, and in heterozygous Rr seeds it was partially
functional. However, in homozygous rr seeds, the SBE-I gene function was
found to be interrupted due to insertion of a small DNA sequence and these
seeds completely lacked amylopectin. This led to an increase in amount of
free carbohydrates and higher osmotic pressures. Therefore, when shrinkage
started on maturation, abrupt loss of large amount of water led to acquisition of
wrinkled phenotype in ‘rr’ seeds. Deep observation of all the phenotypes also
revealed the amount of amylopectin and thereby the round shape of seeds in
Rr was somewhat intermediate between RR and rr. The shape of starch grains
was also quite distinct from each other in all the three genotypes.

Fig. 2.1: Complete Dominance in inheritance of seed shape phenotype in Pea.

Thus simply rendering the round / wrinkled phenotypes in pea seeds to the
phenomenon of dominance was not justifiable and suggested for more insights
into the genetic mechanisms.

2.2.2 Incomplete Dominance (Blending Inheritance or

Semi/Intermediate Dominance)
Another type of interaction between two alleles was discovered by Karl
Correns in 1900, while experimenting with Four O’ Clock plant (Mirabilis jalapa
belonging to family Nyctaginaceae). When he crossed the homozygous plant
with red flowers (RR) with homozygous recessive plant with white flowers
(rr), he noticed a strange phenotype in F1 hybrids. The flowers of heterozygous
(Rr) plants were pink, instead of being red by virtue of dominance. He
concluded that this was due to an intra-allelic interaction in which the dominant
allele could express itself partially in heterozygous condition. Since the
character appeared to be intermediate between the dominant and recessive
phenotypes, the phenomenon was called ‘incomplete dominance’. 49
Block 1 Heredity and Phenotype
Further, if selfing is done among F1 hybrids, the phenomenon of incomplete
dominance persists and phenotypic and genotypic ratios obtained in F2
generation are Red1: Pink2: White1 (Fig. 2.2).

2.2.3 Codominance
Codominance is a phenomenon in which both the alleles are completely
expressed in the heterozygous condition, the phenotype of the
heterozygous individual is a mixture of both. Since the characters
expressed by both the alleles exist simultaneously in equal amount, there is no
appearance of intermediate phenotype in heterozygotes as is seen in
incomplete dominance. Codominance is observed in the MN blood groups of
humans. This classification of human blood is based on the presence of M and
N antigens on the surfaces of red blood cells. The M and N antigens are
produced by a pair of codominant alleles designated as LM & LN. The
homozygous condition of allele LM produces marker antigen M, while an LN
produces marker antigen N, on the surface of red blood cells. Homozygotes
LMLM have only M while LNLN have only N markers, however, heterozygotes L
M N
L have both types of marker antigens in equal amounts on the cell surface. If
a cross occurs between individuals with LMLN genotypes, the probablility of
occurance of M, MN, and N blood types would be as given below:

Red Pink White

1 : 2 : 1

50 Fig. 2.2: Incomplete Dominance in flowers of Mirabilis jalapa.

Unit 2 Extension & Modifications of Mendelian Genetic Analysis-I
Table2.1: Codominance in the MN blood groups in humans.

Genotype Phenotype Antigen present on

RBCs

LM LM M M

LM Ln MN MN

LM LN N N

Another classical example of codominance is inheritance of colour of flower in

Camellia plants. If white Camellia are crossed with red Camellia, the flowers
produced in F1 generation produce flowers with mixed patches of red and
white colour. The alleles for both red and white petal colour are codominant
and both the colours are expressed simultaneously in equal amounts.

Fig. 2.3: Codominance in Camellia flowers.

SAQ 1
i) The allele which is masked or remains unexpressed is called
…………….. .

ii) The flowers of heterozygous (Rr) plants were pink instead of being red
by virtue of ………………. .

iii) ………………. is a phenomenon in which both the alleles are completely

expressed in heterozygous condition, the phenotype of heterozygous
individual is a mixture of both.
51
Block 1 Heredity and Phenotype
2.3 MULTIPLE ALLELES
Multiple alleles refer to the existence of more than two forms of an allele in a
species, which can give rise to a number of variations for a particular
phenotype. Multiple alleles exist within a population and an individual
possesses only two of its forms. Multiple alleles have been found in most
populations including humans and have significant role in genetic stability of
the population. Different allelic forms of a gene differ very minutely in their
nucleotide sequence and thereby exhibit different levels of activity of their
respective gene products. The phenotypes produced by multiple alleles may
thus range from wild type (normal) to mutant. Most of the genes in populations
of most organisms have multiple alleles. The ‘normal’ or ‘wild-type’ allele is
thus not characterized by a single nucleotide sequence, rather it is a set of
different nucleotide sequences, each of which is capable of carrying out the
normal function of the gene.

A classic example of multiple alleles is coat colours in rabits (Fig. 2.4). This
phenotype is determined by a gene that has four alleles denoted differently i.e.
allele C is for wild-type i.e. full colour, ch is for Himalayan characterized by
white coat with black tips, cch is for chinchilla having mixed coat colour and
white hair, and c stands for albino. The range of coat colours also exhibits a
kind of gradation in the order of dominance of the concerned genes, as shown
below-

C>cch>ch>c

Fig. 2.4: Expression of multiple alleles in coat colour of rabbits.

According to this phenomenon, full colour C is dominant to all other coat

colour alleles, chinchilla is dominant to Himalayan and albino, and Himalayan
is dominant only to albino. This gradation has profound effect on the
phenotypic and genotypic ratios of successive generations. The occurrence of
homozygous dominant individuals (CC) is highest and this allele is called ‘wild
52 type’. Rest other alleles (cch, ch and c) are called mutants (Table 2.2).
Unit 2 Extension & Modifications of Mendelian Genetic Analysis-I
Table 2.2: Different Genotypes and their respective Phenotypes for coat colour
in rabbit.

Genotypes Phenotypes
ch h
CC, Cc , Cc , Cc Full Colour (Wild type)

cchcch, cchch, cchc Chinchilla

chch, chc Himalayan

cc Albino

The inheritance pattern of multiple alleles of coat colour in rabbit is explained

on the basis of two crosses between individuals of different phenotypes. When
wild type homozygous full colour (CC) rabbit is crossed with homozygous
recessive albino (cc), the phenotype of F1 heterozygous offspring (Cc)
resembles dominant parent because allele C is dominant over c. The cross
between two heterozygous (Cc) individuals yields coloured phenotype in 3:1
ratio in F2 generation. In another cross, when Himalayan (chch) individual is
crossed with albino type (cc), the F1 heterozygous offspring (chc) show
Himalayan phenotype. The cross between individuals of F1 generation again
yields 3:1 phenotypic ratio in F2 generation (Fig. 2.5).

Fig. 2.5: Cross showing inheritance of coat colour phenotype in rabbits. (a)
Cross between coloured and albino, (b) Cross between Himalayan and
albino.

2.3.1 ABO Blood Type Alleles in Humans

Another common example of multiple alleles is ABO blood types in humans
(Table 2.3). The blood groups in humans are classified as A, B, O, or AB,
depending upon the three types of alleles IA, IB, and IO. Here, ‘I’ denotes an
antigen ‘isoagglutinogen’ which is present on the surface of red blood cells.
There are two types of oligosaccharides, either of which are attached to the
common acceptor isoagglutinogen by the action of enzyme
glycosyltransferase. This enzyme is the product of ABO gene having three
alleles. Allele ‘IA’ encodes for A- glycosyltransferase which converts
isoagglutinogen into A antigen, and allele ‘IB’ encodes for B-
glycosyltransferase which converts isoagglutinogen into B antigen. Allele ‘IO’ 53
Block 1 Heredity and Phenotype
does not encode any of these enzyme, instead produces a different protein,
therefore no oligosaccharide component is attached to its corresponding
isoagglutinogen and it is left unaltered.

The blood group of an individual is determined by the type of allelic pair

present. Both the alleles of blood types i.e. A and B, are codominant and
express completely. Individuals having the genotype IA IA or IA IO have type A
blood group and the ones having the genotype IB IB or IB IO have type B blood
group. Heterozygous individuals IAIB have both A and B types of antigens
therefore their blood group is designated as AB. People having homozygous
allele combination IO IO lack either of the two antigens and their blood group is
designated as O.

Table 2.3: Genotypes and blood groups arising from different allelic
combinations

Genotype Blood Antigen on Antibodies in Can receive Can donate

Type red blood plasma blood from blood to
cells

AO, AA I AI O , I AI A A A anti-B O and A A and AB

BO, BB I BI O , I BI B B B anti-A O and B B and AB

AB I AI B AB A and B neither O, A, B, and AB only

AB

OO I OI O O neither anti-A and O only O, A, B, and

anti-B AB

The ABO antigens are the most immunogenic of all other blood group
antigens, therefore, ABO system of classification of blood group has foremost
clinical significance. The agglutination reactions arising due to incompatibility
of A, B and O antigens are most common cause of death following error or
mismatch in blood transfusions (Fig. 2.6).

Fig. 2.6: Agglutination reaction and subsequent hemolysis due to incompatible

54 blood transfusion.
Unit 2 Extension & Modifications of Mendelian Genetic Analysis-I
The type of blood group is determined genetically and is, therefore, inherited
by a child from his parents. Since the two alleles IA and IB are codominant,
while IO represents a recessive allele, there are number of possibilities arising
for blood type of children. The inheritance patterns can be followed by making
probable parental combinations of alleles (Table 2.4).

Table 2.4: Inheritance pattern of Blood Groups in Humans.

2.3.2 Rh Factor Alleles in Humans

Rh Factor or Rhesus factor is second most clinically significant blood group
system of ABO blood group system. It was discovered by Karl Landsteiner and
AlexanderWiener in 1937 (published in 1940), long after the discovery of ABO
system, when the two biologists carried out immunization experiments on
rabbit using blood of rhesus monkey. They found that the antibodies produced
after immunization, agglutinate the blood of monkey and also the blood of
large number of human subjects. Rh incompatibility can be tested by reacting
a blood sample with anti Rh serum and look for occurrence of agglutination as
a positive response. An individual is either Rh + if his blood agglutinates, or is
Rh- if there is no agglutination in such reaction.

Rh factor is based upon the presence of certain antigens on the surface of

RBCs. Until now, about 49 antigens have been identified, encoded by RHD
and RHCE genes, making it genetically very complex. The D antigen encoded
by RHD is said to be most immunogenic, therefore Rh + phenotype simply
refers to the presence of D antigen while Rh- indicates its absence in the
blood, usually due to deletion of the concerned gene.

Alexander Wienner, discovered a number of Rh antigens and also proposed

their nomenclature known as Rh–hr nomenclature. He postulated a theory
for inheritance of Rh factor, later called Weiner’s theory. The theory suggests
the presence of an Rh gene at a particular locus which has eight multiple
alleles which produce this large array of Rh antigens. The five major ‘blood
factors’ or antigens identified by Wienner were Rh0, rh’, rh”, hr’ and hr”, of
which Rh0, rh’, rh” are encoded by gene R1 and hr’ and hr” are encoded by
gene r. This system of nomenclature is not followed now and is replaced by
the one developed by Ronald Fisher and R.R. Race. It is known as the Fisher-
Race system or DCE nomenclature, and it recognizes five most common
antigens D, C, c, E and e. The antigens C, c, and E, e are antithetical; antigen 55
Block 1 Heredity and Phenotype
D lacks any antithetical antigen therefore ‘d’ is used to indicate absence of D
antigen. In Weinner’s nomenclature, the antigens D, C and E correspond to
Rh0, rh’, rh”, while c and e antigens correspond to hr’ and hr”. The antigen D is
encoded by gene RHD and rest others are encoded by gene RHCE, located
on a separate locus. The two genes constitute eight haplotypes -Dce, dce,
DCe, dCe, DcE, dcE, DCE, and dCE, which are analogous to R0, r, R1, r′, R2,
r″, Rz, and ry respectively in Weinner’s system of nomenclature.

The Rh factor is clinically the second most important blood group system after
ABO blood group and is essentially checked for incompatibility to avoid
agglutination reactions after blood transfusion. It is also responsible for
haemolytic disease in fetus and new born, a condition arising due to
incompatibility between the fetal blood and maternal blood. When Rh- mother
carries Rh+ fetus (gene for Rh+ blood group inherited by fetus from Rh+
father), she is immunized to Rh antigens due to exposure to these antigens.
The first child is not affected, but during subsequent pregnancy, the second
fetus may be exposed to maternal anti-Rh antibodies. These are anti-D IgG,
which can cross the placenta, destruct the antigens on fetal RBCs, and cause
hemolysis. The disease is called hemolytic disease of the newborn (HDN) or
erythroblastosis fetalis, may range from mild to severe, even causing the
death of fetus.

The hemolytic disease of the newborn (Fig. 2.7), which is likely to occur due to
RhD incompatibility, is prevented by injecting anti-RhDimmunoglobulin Rho
(D) in mother at certain stages of pregnancy. IgG Rho (D) binds to fetal Rh
antigens that enter the blood stream of mother and prevent the elicitation of
primary antibody response. This preventive treatment reduces the risk of HDN
in subsequent pregnancy.

Fig. 2.7: Hemolytic disease (Erythroblastosis Fetalis) of the newborn and its
prevention in Rh- mother

2.3.3 Incompatibility in Plants

Incompatibility refers to the prevention of fertilization of male and female
gametes in bisexual plants, despite the gametes are functional. Incompatibility
56 may be seen between the gametes of same species (intraspecific) or between
Unit 2 Extension & Modifications of Mendelian Genetic Analysis-I
different species (interspecific). Intraspecific incompatibility, also known as
self-incompatibility, may operate to prevent fertilization between the gametes
of same plant or the gametes of different plants of same species. The
mechanisms of self-incompatibility are different in case of pre-fertilization and
post-fertilization barriers. The pre-fertilization involves pollen pistil interactions
such as pollen-stigma interaction, pollen-style interaction and pollen-ovule
interaction, in which the pollens may fail to germinate on stigma, if they
germinate the growth of pollen tube may be inhibited or may fail to enter the
ovule for gametic fusion.

Self-incompatibility is controlled by a single gene (designated as S) with

multiple alleles (Fig. 2.8). It was first discovered in tobacco (Nicotiana
tabacum).The multiple alleles of gene S are represented by S1, S2, S3, S4
……..Sn. All the alleles are codominant and either of the two alleles may be
present in a plant. A plant with S1S2 genotype will produce pollens with either
S1allele or S2 allele, which will be able to pollinate the pistil of all other
genotypes except S1S2. In other words, even if single allele is common in
both male and female parent plants, fertilization will not take place (Table 2.5).

Table 2.5: Multiple alleles responsible for Self-incompatibility in plants.

Male Female Genotype Compatibility Fertilization and

Genotype
Seed Production

S1S2 S1S2 Incompatible No

S1S3 S1S2 Incompatible No

S3S4 S1S2 Compatible Yes

S3S4 S2S5 Compatible Yes

Fig. 2.8: Self-incompatibility in plants. 57

Block 1 Heredity and Phenotype

SAQ 2
Read the following statements and write True (T) or False (F) against each:

i) Most of genes in populations of most organisms have multiple alleles.

ii) ABO antigens are the most immunogenic of all other blood group
antigens.

iii) Rh factor is the clinically most insignificant blood group system of ABO
blood group system.

iv) Self incompatibility is controlled by a double gene with multiple alleles.

2.4 GENE INTERACTIONS AND MODIFIED

MENDELIAN RATIOS
The gene interactions studied above are allelic or intragenic, i.e. different
alleles of single gene interact and affect the expression of each other, and
may also lead to the development of a new phenotype. However, there are
interactions in which two or more genes located at different loci are
responsible to produce a phenotype. The expression of these genes is
influenced by each other and interactions among these genes may create new
phenotypic combinations exhibiting modified Mendelian ratios. Such
interactions are called non-allelic or inter-genic interactions.

The different non-allelic interactions discussed here are complementary gene

interaction, epistasis, supplementary gene interaction and duplicate genes.

2.4.1 Complementary Gene Interaction (9:7 Phenotypic

Ratio)
Complimentary genes are a pair of non-allelic genes that are together
responsible to produce one phenotype. Both are dominant but neither is
able to produce the phenotype alone. At least one dominant allele from both
the gene pairs is required to produce the concerned phenotype. In the
absence of any of the dominant alleles, i.e. when any of the recessive pairs is
present, mutant phenotype is expressed. If parents heterozygous for both the
genes are crossed, a phenotypic ratio of 9:7 is obtained in F2 generation.

This interaction is seen in sweet pea (Lathyrus odoratus) in which two genes
designated as C and P contribute in synthesis of anthocyanin to give purple
colour to flowers (Fig. 2.9). The mutant phenotype in this case is white colour
of flowers which appears due to non functioning of enzymes involved in
biosynthesis of anthocyanin.

If a homozygous pea plant with coloured flowers (CCPP) is crossed with

homozygous recessive with white flowers (ccpp), the F1 generation have
coloured flowers (CcPp). However, on selfing the F1 plants, the normal
Mendelian dihybrid ratio (9:3:3:1) is not obtained, instead the interactions of
58 complementary nature between the two genes C and P genes gives a
Unit 2 Extension & Modifications of Mendelian Genetic Analysis-I
modified phenotypic ratio (9:7). A similar cross is described in Figure-2.9 in
which a cross between two homozygous parents with white flowers CCpp and
ccPP yields F1 progeny with purple flowers (CcPp), which on selfing also
exhibit complementary gene action. This cross infers that the anthocyanin
pigment is biosynthesized only when a dominant allele from both the gene
pairs is present, giving purple phenotype. Recessive pair of either of the two
genes renders the enzymes of anthocyanin biosynthetic pathway non-
functional and white flowers are produced.

Fig. 2.9: Complementary Gene Interaction in Lathyrus odoratus.

2.4.2 Epistasis
Epistasis is another kind of gene interaction in which one gene masks the
expression of other non-allelic gene. The gene that shows the masking
action is called epistatic gene while the one whose expression is masked is
called a hypostatic gene.

On the basis of the effect exerted on another gene, epistasis can be of two
types- dominant and recessive epistasis.

a) Dominant Epistasis:This type of gene interaction occurs when a

dominant gene suppresses the expression of a gene at some other 59
Block 1 Heredity and Phenotype
locus. For example, in Cucurbita pepo (summer squash), gene for white
fruit colour is dominant and is designated as ‘W’ (Fig. 2.10). Another
gene ‘Y’ controls the expression of yellow colour in fruit. The gene W
exerts epistatic effect on the gene Y, therefore, the yellow colour is not
expressed in fruits in presence of gene W. When both the genes (W and
Y) are absent, green phenotype appears. The F2 phenotypic ratio in
dominant epistasis is 12:3:1.

Fig. 2.10: Dominant Epistasis in Cucurbita pepo.

b) Recessive Epistasis- In this type of gene action, a recessive pair of

alleles inhibits or masks the expression of a gene at another locus.The
epistatic action is exerted by the homozygous recessive gene pair and
its own expression by its dominant form occurs only in the presence of
other dominant gene.

Coat colour in mice is a common example of recessive epistasis. The

coat colour in mice can be black, agouti or albino, and the phenotype is
controlled by two pairs of genes- ‘A’ and ‘C’, both of which are non-
allelic. The agouti coat colour in mice is expressed by gene ‘A’ only in
presence of another dominant gene ‘C’. However, the recessive pair of
alleles ‘cc’ masks the expression of the gene A, for both the genotypes
AA and Aa. The black coat colour in mice is expressed by gene ‘C’ only
in absence of dominant gene A. Recessive homozygous forms of both
the gene pairs produce albino phenotype. The F2 phenotypic ratio in
such a case is 9:3:4 (Fig. 2.11).

2.4.3 Supplementary Gene Interaction

Supplementary gene interaction also occurs between two non-allelic genes,
each of which is responsible for same trait. This type of gene interaction is
very similar to recessive epistasis. In supplementary gene action, a dominant
60 gene is able to express its character, while another dominant gene, at different
Unit 2 Extension & Modifications of Mendelian Genetic Analysis-I
locus, is able to express itself only in presence of the first one. For example,
coat colour in mice is controlled by two pairs of genes- A and C. Gene C
expresses black coat colour in mice. All the black mice consist of at least one
dominant allele ‘C’ but no ‘A’. Whenever dominant gene ‘A’ is present along
with ‘C’, agouti phenotype appears, i.e. A is expressed only in presence of C.
Presence of either only dominant gene A or recessive forms of both (aa and
cc) produce no colour and give albino phenotype. The F2 phenotypic ratio is
same as in recessive epistasis i.e. 9:3:4 (Fig. 2.11).

Fig. 2.11: Inheritance of coat colour in mice.

2.4.4 Duplicate Genes (Pseudoalleles)

When two non-allelic pairs of genes are able to produce a phenotype, whether
they are alone or together, are called duplicate genes. In such case, the
mutant phenotype is produced by double homozygous recessive condition
only.

Example of duplicate genes is the presence of awn in the spikelet of rice,

which is due to two dominant duplicate genes (A and B). The presence of awn
is a dominant character and can be produced by any of the two genes.
Therefore, the awn is absent in only those plants which are homozygous
recessive (aabb). The F2 phenotypic ratio in such a cross is 15:1 (Fig. 2.12). 61
Block 1 Heredity and Phenotype

Fig. 2.12: Duplicate Genes in rice.

SAQ 3
Match Colum A with Colum B.

Colum A Colum B

i) Complementary Gene Interaction a) A recessive pair of alleles inhibit

or maks the expression of a
gene at another locus.

ii) Dominant Epistasis b) Occurs between two non-allelic

genes for same trait.

iii) Recessive Epistasis c) Two non-allelic pairs of genes

are able to produce a
phonotype.

iv) Supplementary Gene Interaction d) Dominant gene suppresses the

expression of a gene.

v) Duplicate genets e) Genes are a pair of non allelic

genes.

2.5 LETHAL ALLELES

In the previous section, you studied the various gene interactions resulting in
the modification of the ratio of F, individuals. The genetic ratios are also
affected by several other factors. One of them is a class of genes - lethal
62 genes, which you will study in this Section.
Unit 2 Extension & Modifications of Mendelian Genetic Analysis-I
Genes may affect viability as well as visible traits of an organism. The living
beings carrying certain genes are disadvantaged as they have impaired
structural as well as, biochemical functioning. For example, Drosophila flies
having white eyes and' vestigial wings have lower viability than their wild
types. The detrimental physiological effects are apparently associated with the
genes involved, that is, w and vg respectively. Some other genes have no
effect on the appearance of a fly but do influence viability in some ways. Other Tay-Sachs disease
genes have such serious effects that the organisms is unable to live. These (amaurotic idiocy):
are called lethal genes and the alleles involved in the situation are termed as A genetic recessive
lethal alleles. disorder that affects
the central nervous
If the lethal effect is dominant and immediate in expression, all individuals system. Its clinical
carrying the gene will die and the gene will be lost. Some dominant lethals, symptoms are:
however, have a delayed effect so that the organism lives for some time. cherry-red spot in eye
Recessive Iethals present in the heterozygous condition have no effect but macula (the visible
may come to expression when matings between carriers occurs. white portion of the
eye); after 6-9 months
We shall now take up an example for discussion, that clearly illustrates the rapid degeneration of
functioning of these genes. In 1904, shortly after the rediscovery of Mendel's vision and motor
principles, a French geneticist, Lucien Cuénot, while carrying out experimental skills; death at about
crosses on coat colour in mice, found that a gene was not consistent with the 2-4 years of age.
mendelian predictions. He observed from his experiments that the yellow body Huntington’s
colour allele (Y) was dominant and agouti allele (y) was recessive. The disease (HD): A fatal
crosses between two yellow mice (see Fig. 2.13) yielded approximately a 2:1 neurological disorder
ratio of yellow to agouti mice rather than the expected ratio of 3: 1. Further, which is dominant. It
when the yellow individuals (Yy) are crossed to the agouti (yy) Cuénot found is normally
manifested after the
that some agouti progeny are produced. He, therefore, concluded that yellow
age of thirty, but has
mice were heterozygous (Yy) and there were no yellow homozygotes (YY) in
been reported to
the progeny. Later, it was suggested that the yellow homozygotes were occur at all ages, HD
actually lethal, and they died while still in the uterus. It was found that is characterised by
1 mental and physical
approximately of the embryos from yellow by yellow crosses failed to
4 deterioration. There is
develop. Therefore, the observed ratio of phenotypes differs from the expected progressive change in
ratio, as they die very young - much before reaching the reproductive age. personality. As the
disease progresses,
the HD patients
demonstrate twitching
and uncontrollable
muscle spasms.
There is degeneration
of Central Nervous
System. (CNS) and
loss of brain cells.
This leads to fits of
depression, insanity
and suicide. At the
time of death, the
patients have lost
about 25 per cent of
their brain weight.

Fig. 2.13: A cross between two yellow mice, yielding a 2:1 ratio in the offspring. 63
 Block 1 Heredity and Phenotype
Such lethals are by no means exceptional and must always be considered in
populations of plants and animals. Many lethals produce no pronounced effect
at all on the phenotype, but they may make their presence known by a
decrease in the life span or the very elimination of the carrier. It has been
estimated that each human carries, on the average, about six lethal alleles.

How can an allele have a killing action? This perhaps may be the question
arising in your mind. You may .remember that metabolism is the result of
many interlocked biochemical pathways. A defect in just one step can upset
several others. Just one defective step can alter the entire chemistry of the
body. A lethal, by blocking a critical reaction, can interfere with normal
embryological development of any organ, SAY heart. The death of embryo
may then follow. Lethals can thus decrease the chances of survival by causing
various kinds of abnormalities in development and physiology.

Different lethals eliminate individuals at different stages of the life cycle. The
complete lethal removes the carrier before the reproductive age so that those
affected have no offspring, e.g., the allele for yellow coat colour in mice; in
humans the recessive factor for Tay-Sachs disease which kills in infancy, In
humans, the dominant factor for Huntington's disease, a fatal, deterioration
of the nervous system, does not usually express itself before the age of 30.
Such genetic determinants which can result in death but permit the carrier to
live to reproductive age, are often grouped as sublethals. There is actually no
sharp boundary during the life cycle at which lethals act.

2.6 PLEIOTROPY
The action of a gene at the cellular level is unitary, that is, one gene one
Metabolic fate of phenylalanine action. Sometimes the presence of a gene results in a broad spectrum of
phenotypic changes, so that it appears that the gene has multiple action.
normal pathway phenylalanine This phenomenon is called pleiotropy, and is found primarily in higher
organisms where complex and interrelated developmental events occur.
enzyme phenylalanine
hydroxylase Many lethal alleles are pleiotropic. For example, the yellow coat colour in
mice, just discussed, is an allele that affects more than one character, that is,
converted to tyrosine it produces yellow colour of the coat in heterozygotes, and it also affects
survival, causing lethality in homozygotes. Another example of multiple effects
normal brain function is the gene affecting seed shape in garden peas; this gene also affects
(a)
starch grain morphology. In fact, many genes affect more than one trait.
PKU – double recessive Mendel also noticed that genes causing the flower colours, like violet and
pathway phenylalanine
white, also influenced seed colour and caused the presence or absence of
coloured areas on the leaves. This is due to pleiotropy as a single gene affects
lacks enzyme phenylalanine more than one character.
hydroxylase

Pleiotropic traits also occur in humans. One such disease is phenylketonoria,

converted to phenylpyruvic acid abbreviated as PKU. This occurs in individuals that are homozygous for a
→ urine
defective, recessive allele. The diseased people lack the enzyme necessary
for the metabolism of the amino acid phenylalanine. When normal and PKU
mental retardation
(b) individuals are compared, the level of phenylalanine is much higher in
diseased group. In addition to this basic biochemical difference, a number of
other features are seen in the untreated PKU patients, such as lower IQ,
64 similar head size and lighter hair.
Unit 2 Extension & Modifications of Mendelian Genetic Analysis-I
2.7 SEX-LIKED GENES
In the crosses we have discussed so far, it has not mattered which parent
carried a particular allele in question. Reciprocal crosses gave identical
results. For example, in all the Mendel's monohybrid crosses, F1 and F2 were
the same regardless of which P1 parent exhibited the recessive trait.

This, however, is not the case in crosses involving genes located on

chromosomes involved in the determination of sex. Such genes are said to be
sex-linked. The first thorough study of the sex-linked gene was conducted by
T.H. Morgan in 1910, when he was studying the inheritance of eye colour in
Drosophila. The wild-type flies have brick red eye colour. Morgan crossed
mutant white-eyed flies with red-eyed flies. He found that the result of a cross
between a white eyed male (rII) and red-eyed female (RIIR) were different
from those of a cross between white-eyed male. Both of these reciprocal
crosses are illustrated in Fig. 2.14. (crosses a and b).

Fig. 2.14: Crosses a and b 'illustrate inheritance of sex-linked genes in

Drosophila. a) is a cross between red-eyed female and white-eyed
male. And b) is the reciprocal cross of a). In the figure the long, rod-
shaped structure (I) represents the X-chromosome and the inverted J-
shaped structure (l) stands for the Y chromosome.

Compare the phenotypic ratios of F2 generations of cross a with b. Is there any

difference? Yes, there is a clear difference between the F2, individuals of the
two crosses. The phenotypic ratios thus depend on whether the P, white-eyed
parent was male and female. Morgan was able to correlate these observations
65
 Block 1 Heredity and Phenotype
with a difference found in chromosome composition between male and female
Drosophila. It has four chromosomes and one of the chromosome varies
between sexes (see Fig. 2.15). This chromosome pair (see XX or XY in the
figure) is involved in sex determination mechanism and constitutes the sex
chromosomes. The remaining chromosomes are called autosomes. The
females possess two, rod-shaped homologs called the X chromosomes which
are designated as XX. Males possess a single X chromosome and J-shaped Y
chromosome, which are designated as XY.

On the basis of this correlation, Morgan postulated that the gene for white eye
is present on the X chromosome but is absent from the Y chromosome.
Females thus have two available genes, one on each X chromosome while
males have only one available gene on their single X-chromosome. 'This
explanation supposes that the Y chromosome lacks homologous loci to these
on the X chromosome. However, the X and Y chromosomes still behave as
homologues in that they do partially synapse with each other and segregate
into gametes during meiosis.
Many species, including humans, possess an arrangement of sex
chromosome as in Drosophila. Many sex-linked genes in humans have now
been identified, e.g., the gene controlling one form of haemophilia and
muscular dystrophy. We stop further discussion on this topic for the time being
and shall resume it in an elaborated manner in Unit 4, that is, Sex Linkage and
Dosage Compensation.

2.8 DEGREES OF GENE EXPRESSION

In observing offsprings from a cross, we tend to think of a phenotype in terms
of all or none of the phenomena. A trait is expressed or it is not - and we draw
conclusions as to what are the types of genotypes based on that form of
expression. While it is true that some phenotypes are always certain, such as,
Fig. 2.15: Chromosomes
in pea plants the genotype ss will produce always the wrinkled seeds.
composition in Similarly, all of the Mendel’s genes and all blood group types show an
Drosophila absolute arid clear cut pattern. However, for some genes, the expression is
melanogaster. variable.

2.8.1 Penetrance
Some individuals fail to slow particular trait, even though genetic analysis
indicates that the controlling gene for that trait must be present in them. This
aspect of gene action, that is the frequency with which a genotype is
expressed in the phenotype is called Penetrance. For example, out of the
eight individuals of a particular genotype, five express the diseased
phenotype. The penetrance is 5/8 = 0.625 or 62.5%.
A completely penetrant gene is always expressed; an incompletely
penetrant gene may be expressed in some individuals, but not in others.
Incomplete penetrance of a gene may cause a trait to skip a generation; that
is, a dominant trait present in a given generation may skip the first generation
but appear again in the second generation. Such a case is illustrated in Figure
2.16. It shows a human pedigree where unaffected individual II-4 is the
daughter as well as the mother of an affected individual each. This indicates
she has the genotype Aa, but because of incomplete penetration, does not
66 show the dominant phenotype.
Unit 2 Extension & Modifications of Mendelian Genetic Analysis-I

Fig. 2.16: A pedigree illustrating the pattern of phenotypes with an incompletely

penetrant dominant allele.

2.8.2 Expressivity
Expressivity refers to the intensity or range of expression of a trait in different
parts of the same individual or different individuals. This aspect of gene action
differs from penetrance in that it describes the level of phenotypic expression,
whereas penetrance refers to whether the phenotype is affected or not. Both
penetrance and expressivity originate from variations in the degree to which a
gene is manifested in the phenotype. These manifestations can be absent or
be so slight as to pass unnoticed; in such individuals, a trait would be
considered non-penetrant. However, when apparent in the phenotype, the
same trait may vary in its effects from mild to severe, in which case the trait
would be described as exhibiting not only variable penetrance, but variable
expressivity as well.

Let us consider the example of Drosophila. In this the recessive allele eyeless
(e) when present in homozygous condition causes a reduction in the size of
the compound eye. However, the extent to which the eye is reduced varies
considerably from individual to individual. In some, only slight decrease in eye
size occurs, while in others the eye may be completely absent. There are also
cases in which the fly has one normal eye and the other eye drastically
reduced in size. Phenotypic variation can also be observed in humans.
Polydactyly exhibits variable penetrance, it is also characterised by differences
in expressivity. In different individuals showing this trait, extra digits may be
present on the hands or on the feet or both hands and feet.

The source of this variation is partly genotypic and partly environmental. The
genotype contains thousands of genes, and the actions of many of them are
interrelated so as to modify one another's effects. For example, the level of
expression of a trait is generally more similar among relatives than among
unrelated individuals, provided that the relatives and unrelated individuals are
raised in fairly similar environments. Such genes that have secondary effect
on a trait are called modifier genes, and can sequentially influence the
phenotype. The modifier genes can be seen in animals like house cat, where a
'dilute allele' reduces the intensity of pigmentation from black to grey. Another
example of modifier genes is seen in D. melanogaster mutants when these are
kept in laboratory culture for many years, sometimes they do not have as
extreme a phenotype as was first observed. 67
Block 1 Heredity and Phenotype
2.9 SUMMARY
Let us sum up what we have learnt in this unit:

• The dominance is a phenomenon of suppression of expression of one

allele by another. The allele that is able to express its phenotype is
called dominant, while the one whose expression is suppressed is called
recessive.

• In heterozygous condition, i.e. when the dominant and recessive alleles

occur together, if an intermediate phenotype appears due to blending of
traits of both alleles, it is called incomplete dominance.

• Further in heterozygous condition if the phenotype of both dominant and

recessive alleles express equally, the phenomenon is called co-
dominance.

• Certain phenotypes are controlled by more than two alleles, known as

multiple alleles, for example the range of coat colour phenotype in
rabbits, ABO blood groups in humans and self- incompatibility in plants.

• There are some non-allelic gene interactions which may give rise to new
phenotypes and are exemplified by modified mendelian ratios. These
are complementary gene interaction, epistasis, supplementary gene
interaction and duplicate genes.

• In complementary gene interaction, neither of the two dominant alleles of

complimentary gene pair is able to produce the phenotype alone. At
least one dominant allele from both the gene pairs is required to produce
the concerned phenotype. The F2 phenotypic ratio in this case is 9:7.

• In another kind of gene interaction, one gene masks the expression of

other non-allelic gene, known as epistasis. If the epistatic gene is
dominant, it is called dominant epistasis, while if the masking action is
due to a recessive gene, it is called recessive epistasis. The F2
phenotypic ratio in both the cases is 12:3:1 and 9:3:4 respectively.

• The gene interaction similar to recessive epistasis is supplementary

gene action in which a dominant gene is able to express its character,
while another non allelic dominant gene is able to express itself only in
presence of the first one. The F2 phenotypic ratio in this case also is
12:3:1.

• A non-allelic gene interaction is observed in which the presence of any

one dominant allele of the two gene pairs also produces a phenotype
and the mutant phenotype appears only in double homozygous
recessive condition.

2.10 TERMINAL QUESTIONS

1. Discuss the genetic basis of seed shape in peas.

2. State reason for appearance of pink flowers as an intermediate

68 phenotype in Mirabilis Jalapa.
Unit 2 Extension & Modifications of Mendelian Genetic Analysis-I
3. How is co-dominance different from incomplete dominance?

4. Explain the occurence of a range of coat colour phenotypes in rabbits.

5. Predict the blood group of a child if blood group of mother is ‘AB’ and
that of father is ‘O’.

6. Explain the clinical significance of Rh antigens in human blood.

7. Describe the role of multiple alleles in self-incompatibility in plants.

8. Explain the complimentary gene action with example.

9. Explain the phenomenon of masking the expression of gene by another

in epitasis.

10. Do you opine that the phenomena of recessive epistasis and

supplementary gene interaction are same or different, explain.

11. Attribute the reason to obtain F2 phenotypic ratio 15:1 in appearance of

awn character in rice.

2.11 ANSWERS

Self Assessment Questions

1. i) recessive, ii) dominance, iii) co-dominance.

2. i) T, ii) T, iii) F, iv) F.

3. a) v, b) iv, c) i, d) ii, e) iii.

Terminal Questions

1. Refer to Sub-Section 2.2.1.

2. Refer to Sub-Section 2.2.2.

3. Refer to Sub-Section 2.2.3.

4. Refer to Section 2.3.

5. Refer to Section 2.3.1

6. Refer to Sub-Section 2.3.2.

7. Refer to Sub-Section 2.3.3.

8. Refer to Sub-Section 2.4.1.

9. Refer to Sub-Section 2.4.2.

10. Refer to Sub-Section 2.4.3.

11. Refer to Sub-Section 2.4.4. 69

Block 1 Heredity and Phenotype
FURTHER READINGS
1. Principles of Genetics by Gardner, Simmons, Snustad, 8thedition – John
Wiley and Sons, Inc., 2003.

2. Genetics: a Conceptual Approach, 3rdedition, Peter J. Russell. Pub: WH

Freeman & Co.

3. Genetics: Principles and Analysis, 4thedition. D.L. Hartl, D.W. Jones.

Pub: Jones and Barlett Publishers

4. Genetics, 9threvised multicolor edition. P.S. Verma & V.K. Agarwal. Pub:
S. Chand & Co.

Acknowledgement of Figures
Fig. 2.1: http://legacy.biotechlearn.org.nz/layout/set/lightbox/themes/
mendel_and_inheritance/mendel_s_principles_of_inheritance

Fig. 2.3: https://biologywise.com/codominance-explained-with-examples

Fig. 2.4: https://courses.lumenlearning.com/bio1/chapter/reading-multiple-

alleles/

Fig. 2.5: http://www.eplantscience.com/index/genetics/multiple_alleles_

based_on_classical_concept_of_allelomorphism/skin_colour
_in_rodents.php

Fig. 2.6: https://courses.lumenlearning.com/microbiology/chapter/

hypersensitivities/

Fig. 2.7: https://courses.lumenlearning.com/microbiology/chapter/

hypersensitivities/

Fig. 2.9: http://www.biologydiscussion.com/genetics/gene-interactions/gene-

interactions- allelic-and-non-allelic-cell-biology/38795

Fig. 2.10: http://www.biologydiscussion.com/genetics/gene-interactions/ gene-

interactions -allelic-and-non-allelic-cell-biology/38795

Fig. 2.12: http://www.biologydiscussion.com/genetics/gene-interactions/top-6-

types-of-epistasis -gene-interaction/37818

70