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@TN Bhusal, PhD

Gene Regulation
• The process of controlling which genes in a cell's DNA are
expressed (used to make a functional product such as a protein)
• Alternatively, how a cell controls which genes, out of the many
genes in its genome, are "turned on" (expressed)
• Different cells in a multicellular organism may express very
different sets of genes
• The set of genes expressed in a cell determines the set of
proteins and functional RNAs it contains, giving it its unique
properties
• A cell's gene expression pattern is determined by information
from both inside and outside the cell
• Gene expression can be regulated at several different levels-
transcription, mRNA processing, mRNA turnover, translation
and enzyme function
• Regulation of transcription is the most important mode of the
control of gene expression

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Terminology
Regulatory genes:
Genes that are involved in turning on or off the
transcription of structural genes
Eg., the gene i of E. coli in lac operon
Structural genes:
Genes that code for (through mRNA) the amino
acid sequence of a polypeptide
Eg., z, y, α genes in E. coli
Regulatory protein:
The product of regulator gene, which regulates
the action of another gene
 Eg., repressor protein produced by gene i
Cistron:
A segment of DNA which code for one
polypeptide; the unit of function; identified by
cis-trans or complementation; generally
accepted as a synonym for gene
Operator gene:
A gene which is located at the
beginning of the operon from
which the transcription begins
and is continuous with the
structural genes transcribed
first, i.e., it is just upstream of
the first structural gene
Eg., operator gene ‘o’ in the lac
operon system in E. coli
Promoter gene:
A gene which is located just
upstream of the operator and
provides the binding site for
RNA polymerase, which carries
out transcription
Eg., p gene in E. coli

Lac Operon Model: inducible operon

 Proposed by F. Jacob and J. Monod in 1961 to explain the regulation of genes encoding
the enzymes required for lactose utilization in E. coli
 Contains a promoter, an operator, and three structural genes z, y and α
 Gene z: coding enzyme β-galactosidase that cleaves lactose into glucose and galactose
 Gene y: coding enzyme β-galactoside permease that “pumps” lactose into the cell
 Gene α: coding enzyme β-galactoside transacetylase

Operon
 The complete contiguous unit, including the structural gene, or genes, the operator
and the promoter

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i gene: lac regulator gene

 Code for a repressor that is 360 amino acids
 Active form of lac repressor is a tetramer that contains four
copies of i gene product
 In absence of inducer, the repressor binds to lac operator
sequence
 that prevents RNA polymerase from binding to the
promoter and transcribing structural genes
Allolactose- the operon inducer
 Derived from lactose in a reaction that is catalyzed by β-
galactosidase
 Once formed, it binds to repressor, causing it to be released
from operator
 In so doing, it induces transcription of the z, y and α
structural genes

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Catabolite activator protein (CAP)-Cyclic Adenosine Monophosphate (cAMP)

• Is a sequence specific DNA binding protein that
stimulates the transcription of lactose catabolizing
genes
• CAP: also known as cAMP receptor protein (CRP)
which is the product of gene ‘crp’
• cAMP: made from ATP with the aid of enzyme
adenylate cyclase produced by gene ‘cyn’
• Both genes presence to left of the promoter
(upstream)
• Stimulates the initiation of transcription by
approximately a factor of 50
• Major factor in this stimulation is recruitment of
RNA polymerase to promoters to which CAP is
bound
• Act as a positive regulator because its presence is
required gene expression
• Presence of glucose interfere or lower the
intracellular concentration of cAMP with the result
cAMP-CRP complex could not formed

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Transposable Genetic Elements or Transposons

• Also known as “jumping genes”, are DNA sequences that move from one
location on the genome to another
• Can move from one location in a chromosome to another within the same
chromosome or into another non-homologous chromosome
• Discovered by Barbara McClintock through an analysis of genetic
instability in maize
• Make up the major content of eukaryotic genome
~50% of human genome
Barbara McClintock
~75% of maize genome
~85% of barley genome
• e.g., IS elements, bacteriophage Mu (in prokaryotes), Ac/Ds system, Ty
elements (in eukaryotes)
What jumping genes do?
 Mutation
Can produce easily tractable mutation
Can produce large number of mutants at low cost and high speed
 Disease development: colon cancer
 Can encode siRNAs that mediate their own silencing

Types of Transposable Elements (TEs)

Retrotransposon vs DNA transposons
 Retrotransposon or Class 1 TE require reverse transcription in
order to transpose
e.g. Copia element, Gypsy element in Drosophila
Move through the action of RNA intermediate
Do not encode transposasae but contain flanking region
 DNA transposons or Class 2 TE do not require reverse
transcription
e.g. Ac/Ds in maize
Autonomous class 2 TE encode the protein transposasae, which
they require for insertion and excision
Never use RNA intermediate, instead always move on their own
by means of “cut and paste” mechanism
Characterized by presence of terminal inverted repeats (9-40bp) in
both ends
Contain flanking direct repeats which play role in insertion of the
TE

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Autonomous vs non-autonomous
Both class 1 and class 2 TEs can be autonomous or non-
autonomous
Autonomous TEs move on their own because they have the
gene for transposasae
Non-autonomous TEs require the presence of other TEs in
order to move because they lacks transposasae or reverse
transcriptase that required for transposition
Ac element is autonomous i.e. self-activating while Ds
element is non-autonomous i.e. not self-activating
Simple vs composite transposons
• Simple transposons: e.g. Tn3
Also carry resistance gene but do not terminate with IS
elements (instead have repeated sequence)
Transposition elements are encoded in the central region
Causes target site duplications
• Composite transposons: e.g. Tn10
Created when two IS elements insert near each other
Have two IS elements flanking a region that contains one or
more genes for antibiotic resistance

• Ac (activator) consists of 4563 Ac/Ds system in maize

bp bounded by an 8 bp direct
repeat
• When the element inserts into
a site on a chromosome, this
direct repeat is created
• Have inverted terminal repeats
(11 bp) and is structurally
similar
• Contain a single gene that
encodes a transposase enzyme
• In Ds (dissociation) structural
heterogeneity observed and
cause chromosomal breakage
• Transpose in the presence of
Ac elements

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IS elements in Bacteria
• Commonly found in bacterial
chromosome (e.g. IS1) and plasmids (e.g.
IS10)
• Range in size from 768bp to 5kb
• Have a single coding sequence with short
(9-40 bp), identical or nearly identical
sequences at both ends (called inverted
terminal repeats)
• When IS elements insert into
chromosomes, they create a duplication of
the DNA sequence at the site of insertion.
One copy of the duplication is located on
each side of the element. These short (3-
12 bp), directly repeated sequences are Integration of IS element in chromosomal DNA
called target site duplications

Features of Transposable Elements

 Autonomous TEs possess a gene that codes for a transposase enzyme which role is to
perform the recombinational events that permits transposon insertion into possible target
sites
 Retrotransposon produce RNA transcripts and they rely upon reverse transcriptase enzyme
to reverse transcribe RNA sequences back into DNA which is then inserted into target site
 Transposition is non-homologous recombination, with insertion into DNA that has no
sequence homology with the transposon
 The frequency of transposition is low, and may be affected by environmental conditions
 Transposons can grow or diminish by accumulating or losing DNA sequence
 These elements can affect gene expression
 Elements can insert in many locations in host

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GENETIC VARIATION
• There are three primary sources of genetic
variation
1. Mutations are changes in the DNA. A
single mutation can have a large effect, but in
many cases, evolutionary change is based on Genetic shuffling is a source of variation
the accumulation of many mutations.
2. Gene flow is any movement of genes from
one population to another and is an important
source of genetic variation.
3. Sex can introduce new gene combinations
into a population. This genetic shuffling is
another important source of genetic variation.

MUTATION
• Is a sudden heritable change in a characteristics of an
organism
• Is the result of a change in a gene (viz. addition, deletion or
substitution), in chromosome(s) that involves several genes
(viz. structural change) or in a plasmagene

Terminology
Mutable genes: genes that show exceptionally high rates of
spontaneous mutations
Mutator genes: genes that increase the spontaneous mutation
frequency of some other genes of genome
Anti-mutator genes: genes that suppress the mutation of
other genes of the genome
Hot spots: the highly mutable sites within a gene
Mutagen: a physical or chemical agent that changes genetic
material i.e. DNA of an organism and thus increases
frequency of mutations above the natural background level Fig. Normal pale grass blue butterfly (top)
and mutated variety (below)

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Characteristics of mutation
• Mutant alleles are generally recessive to their
wild type or normal alleles
• Mutations are generally harmful to the
organism
• Mutations are random i.e. may occur in any
gene or at any time
• Mutations are recurrent i.e. the same mutation
may occur again and again
• Induced mutations commonly show
pleiotropy
• Rate of spontaneous mutations for most gene
is very low (10-7 to 10-4) and also varies
considerably from one gene to another
• Mutagens increase the frequency of mutations
• Can occur in any tissue/cell or an organism
• Can occur during developmental stage of
organisms
• Can occur in both reverse and forward
directions
• Mutant alleles produced by deletion do not
mutate back
4. On the basis of cause of mutation/origin
• Spontaneous mutations or Natural
Mutations: when mutations occur
naturally at a low rate
• Induced mutations: induced by a
treatment with certain physical or chemical
agents in laboratory
5. Based on their directions
• Forward mutation: development of a new
mutant type from a wild type (normal type)
• Reverse mutation - Back mutation:
mutants revert to normal type
6. Based on character
• Morphological: a mutation that alters
morphological character of an individual
• Biochemical: a mutations that alters
biochemical function of an individual
7. Based on affecting factors
• Endogenous mutation: Caused by certain
internal factors like change in metabolism,
nutrition etc.
• Exogenous mutation: Caused by external
factors like change in temperature, other
climatic factors, etc.
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Classification
1. Based on tissue of origin
• Somatic mutations : mutations occurring in body
cells and such mutation are not transmitted to next
generation and hence termed as non-heritable
mutations
• Germinal mutations : mutations occurring in
reproductive cells and such mutations are heritable
and passed on to next generation
2. Based on nature of mutation/cytological basis
• Gene or point mutation: mutation produced by
changes in base sequences of genes
• Chromosomal mutation: mutation produced by
changes in chromosome structure or even in
chromosome number
• Cytoplasmic mutation: mutations associated with
mitochondrial or chloroplast DNA
3. Based on type of chromosomes
• Autosomal: mutation occurring in autosomes
• Sex linked mutations: mutations occurring in sex
chromosomes
8. Based on stages of occurrence
• Gametic mutation: mutation occurs during gamete
formation
• Zygotic mutation: Occur during first or later mitotic
divisions in a zygote. This results in the development
of mutant characters only in the cells which are
involved in the process. Here a mosaic organism is
formed.
9. Based on visibility
• Macro-mutations: mutation with distinct
morphological changes in phenotype; found in
qualitative characters
• Micro-mutations: mutation with invisible phenotypic
changes; observed in quantitative characters
10. Based on effects on survival
• Lethal mutation: kill each and every individual that
carries them in appropriate genotype
• Sublethal and Subvital mutation: Reduce viability,
but they do not kill all the individual that carry them in
appropriate genotypes
• Vital mutation: Do not reduce viability of individual
carrying them in appropriate genotype
• Super vital: enhance survival of those individual that
carrying them as compared to wild individual
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MUTAGENES
Physical mutagen
• All of them are various kinds of radiation
1. Ionising radiation
• Particulate radiation: α- rays (DI), β-rays (SI), fast
neutrons (DI) and thermal neutrons (DI)
• Non-particulate radiation (electromagnetic
radiation): γ-rays (SI), X-rays (SI)
2. Non-ionizing radiation: Ultra-violet radiation
Chemical mutagen
1. Alkylating agents: Sulphur mustards, nitrogen
mustards, imines (e.g. ethylene imine (EI)), sulphates
and sulphonates (e.g. ethylmethane sulphonate
(EMS), methylmethane sulphonate (MMS)), nitroso
compounds (e.g. MNNG), etc.
2. Acridine dyes: acriflavine, proflavine, ethidium
bromide, acridine orange or yellow
3. Base analogue: 5-bromouracil, 5-chlorouracil
4. Others: nitrous acid, sodium azide, hydroxyl
amine

TYPES OF GENE MUTATION/MOLECULAR BASIS

1. Base substitution
• When one base in a DNA molecule is replaced by
another one
• Causes two types of molecular changes
a. Transition
• When a purine is replaced by another purine or
pyrimidine is replaced by another pyrimidine
b. Transversion:
• When a purine is replaced by a pyrimidine or vice-versa
Base substitutions causes different types of mutation at
coding regions
Missense mutation: change from one amino acid to
another
Silent mutation: change in codon such that same amino
acid specified
Non-sense mutation: change from an amino acid to stop
codon
Neutral mutation: change from one amino acid to
another amino acid with similar chemical properties

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Molecular changes and mutation at coding region

due to Base pair substitution
2. Base addition and deletion
Base insertion or addition: insertion of one or
more bases in DNA molecule
Base deletion: a loss of one or more bases from
DNA molecule

• If the no. of bases added or lost is a multiple

of 3, one or several amino acids would be
either added to or deleted from concerned
polypeptide and have no profound effect on
activity of protein

• If the no. of bases added or lost is not a multiple of 3. Transposition

3, the base sequences of all codons beyond the
point of insertion or deletion are altered
• Consequently, all the codons beyond this point
will now code for a different amino acid as
compared to that encoded before
• The reading frame of subsequent codons is shifted
in such mutations and hence they are called frame
shift mutations
• Transposable elements: DNA
sequences that can move from one
location in genome to another
• The movement of transposable
elements is known as transposition
• Integration of a transposable element
within a gene often inactivates the
gene, e.g., allele producing wrinkled
seed in peas
• Movement of a transposable element
out of a gene may restore its function
i.e. reverse mutation

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PRACTICAL APPLICATION OF MUTATION

Mutation breeding/Mutagenesis
a) Production of plant, animals and microbial varieties with desirable traits
Crop with high yield (e.g. rice, wheat), early maturity (e.g. castor, rice), high protein content
(e.g. wheat), resistance to disease (e.g. oat, wheat, barley, groundnut), frost and lodging,
increased oil content (e.g. mustard), low toxin content (e.g. lathyrus, rapeseed & mustard), etc.
Could replace conventional breeding procedures to a great extent
Has been achieved big success in animal and microbial breeding
Table: List of cultivated crops and their cultivars developed through mutation breeding
Cultivated crops Cultivar isolated Mutation used Improved attributes
Oryza sativa Jagannath, Kashmir EMS, fast neutrons, sodium Amylose content, blast resistance,
basmati, Vijaya azide, X & γ rays longer grain, semi dwarf, increase
tillers, yield
Triticum aestivum Arjun, Sonalika, Sharbati γ rays, Hydroxylamine, NMU, Grain colour, maturity time, protein
Sonora, Aurora, Kalyan EMS, Fast neutrons, content, lodging resistance, strong
sona Microwaves straw, yield
Solanum tuberosum IR-23 X-rays Resistance to late blight
Saccharum officinarum Co8808, Co997,Co449 γ rays Resistance to red rot

b) Induction of male sterility

Genetic male sterility: durum wheat
Cytoplasmic male sterility: barley, sugar beet, pearl millet, cotton
c) Production of haploid
X-ray irradiated pollens help in production in haploid
Chromosomal doubling of these haploids results in the development of inbred lines
which can be utilized in the development of commercial hybrids
d) Creation of genetic variability
Use for increasing the range of genetic variability through induced mutation for various
economic characters of some plants (e.g. barley, oat, wheat)
Somatic mutation become useful in asexually propagated plant (e.g. potato, sugarcane)
e) Overcoming self-incompatibility
Mutations of S gene by irradiation offers a solution to production of self-fertile plants in
self-incompatible species (e.g. Prunusovium)

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Mutation and Industry

• Widely employed in industry: increase in antibiotic production from bacteria and fungi
1500 times more penicillin production than original strain of fungus (Penicillium
chrysogenum)
Several folds increment of productivity of yeast

Mutation and Evolution

• Characteristically brings about permanent changes in morphological, physiological and
genetical attributes of a species
• If mutation is desirable and non-lethal, then mutated species would adapts itself to new
environment
• Also effect the compatibility between species (incompatibility in original vs mutated species)
• Gene mutation, structural change and numerical change have vital role in evolution of new
species and races

CHROMOSOMAL ABERRATION OR ABNORMALITY OR ANOMALY

• are departures from the normal set of chromosomes
either for an individual or from a species
• refer to changes in the number of sets of
chromosomes (ploidy), changes in the number of
individual chromosomes (somy), or changes in
appearance of individual chromosomes through
mutation-induced rearrangements
• variation arise in chromosomal number or structure in
nature caused by mutation or spontaneous (without
any known causal factors)
• can be associated with genetic diseases or with species
differences

Grouped in two broad classes:

1. Structural aberration
2. Numerical aberration

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1. STRUCTURAL ABERRATION
(changes in chromosome structure)
• Chromosome aberrations in which they alters the
structure of chromosome (sequence of genes or kind
of genes in chromosomes or no. of genes)
• arise from the incorrect repair of breaks in a
chromosome caused by viruses, chemicals, radiation
or other events
• Aberrations arise in germ cells are most important Fig: Types of structural aberrations

Types of structural aberrations

1. Deletion or deficiency
• First chromosome aberration discovered by Bridges (1917) in Drosophila
• Occurs when a chromosome losses a segment due to breaks
• Results in partial monosomy for affected region
• If deletion covers a large area, affected individual will not be viable

• Usually detected by based on unpaired region of normal chromosome produces a loop during
pachytene stage
• Usually caused either by mis-division of centromere or radiation, UV, Chemicals, viruses
(may increase breakage)

Classification of Deletion
a) Terminal deletion b) Interstitial or intercalary deletion
• In which the deletion remove one of the ends • In which the central portion of
of a chromosome chromosome is lost
• Lost segment includes telomere • A segment between telomere and
centromere is lost

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Effects of deletion 2. Duplication

• Pseudo-dominance: due to non-
lethal deficiency
• No crossing over: completely absent
• Harmful effect on diploid organisms:
lethality
• Most are as recessive lethals
• Morphological effects: unique
phenotype effect of their own
Disease caused by deletion
• Cri-du-chat (Cat like cry) syndrome:
5p- (5p minus) syndrome
• DiGeorge syndrome: chr 22
• Wilm’s tumor: chr 1, 11, 16, 22
• Angelman syndrome: 15q11. 2-q13
deletion
• Prader-Willi syndrome: 15q11-13
deletions
• Reported by Bridges in 1919
• Result from the doubling of chromosomal segments
and occur in a range of size and locations
• Alternatively, chromosome segment present in
multiple copies
• Usually caused either by abnormal events during
recombination (unequal crossing over) or
chromosome breakage and reunion of chromosome
segments
• Results in un-paired loops
visible cytologically

Classification of Duplication
a) Tandem duplication
• Repeated segments are adjacent to each other
b) Reverse tandem duplication
• results in gene arranged in the opposite order of the
original
c) Terminal tandem duplication
• tandem duplication at the end of a chromosome
d) Displaced
i) Homobrachial displaced
• Additional segments will be adjacent to original segment
but in a displaced position in the same arm of chromosome
ii) Heterobrachial displaced
• Duplicated segment is present on different arm of same
chromosome
e) Transposed/Translocated duplication
• Duplicated segment of chromosome becomes attached to a
non-homologous chromosome
• May be either interstitial or terminal

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Effects of duplication 3. Inversion

• Evolution
origin of new genes mainly due to
duplication result evolution
Produce wild type phenotype due to
duplication of recessive alleles
• Position effect
Drosophila bar eye: duplication of 16A
region of X-chromosome
• Activity of certain genes may be doubled
Chromosome 6 of barley increased the
activity of α-amylase
Disease caused by duplication
• Charcot-Marie-Tooth disease type
duplication at 17p11.2
• Identified by Sturtevant (1926) in
Drosophila for first time
• Are rearrangements of gene order
within a single chromosome due to
incorrect repair of two breaks
• Occurs when chromosome segment
become detached and reinserted in such
a way that the gene order is reversed
• Alter gene sequence by the rotation of
gene block by 180o
• Detected by
Presence of twisted double loop
during pachytene
Comparing with the normal strain
by using linkage map
1A:
Presence of abortive pollen

Classification of inversion
a) Paracentric inversion
• Inverted chromosome segment does not include
centromere
• Formation of two abnormal chromatids through
single crossing over within the inversion loop
one with two centromere (dicentric) and
other with no centromere (acentric)
b) Pericentric inversion
• Inverted chromosome segment include
centromere
• Out of four chromatids
one would be normal,
other with inverted segment
rest two show deficiency and duplication

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Effects of Inversion 4. Translocations

• Lead to origin of new species
• Partial male sterility (pollen sterility)
• Formation of recessive mutation
• Position effect
• Effect the activity of NOR of
complement chromosome
• Move active gene to sites generally
inactive; lose gene function and
vice-versa
• Suppression of crossing over in
inversion heterozygotes
• First observed by Bridges (1923) in Drosophila
• chromosome segment transferred to a different part
of the same chromosome or to a non-homologous
chromosome
• A kind of chromosomal rearrangement in which a
block of genes from one linkage group is
transferred to another linkage group
• Occurs spontaneously or induced by mutagens
• Detected by
Formation of cross shaped configuration at
pachytene between two non-homologous
chromosome
Ring of 4 chromosome at metaphase 1 due to
pairing between homologous chromosome
Presence of abortive pollen and low seed set

Classification of Translocation
a) Reciprocal translocation
• Result when two non-homologous chromosome exchange pieces
• Single break occurs in two non-homologous chromosome followed by exchange of broken
segment between them
i. Homozygous translocation: both pair interchanged their segments
ii. Heterozygous translocation: one pair of chromosomes interchanged their segments
and one pair is normal

Fig. Reciprocal translocation

b) Simple translocation Fig. Simple translocation

• Which involve a single break in the chromosome and the transfer of a broken piece of this
chromosome directly onto the end of another

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C) Shift or Intercalary translocation Effects of translocation

• Are more common and are translocations involving three • Evolution (due to change in
breaks, so that a two break section of one chromosome is chromosome number)
inserted within the break produced in the non-homologous
chromosome • Position effect
d) Robertsonian translocation • Damage to DNA may result
• Caused by the fusion of the long arm of two acrocentric in formation of recessive
chromosomes lethals
• Involve any two acrocentric chromosomes, which experience • Lead to semi sterility/partial
break near centromere and result in a way that results in the sterility
fusion at the centromere of the q arms and lost of p arm • Complications to synopsis
• Most common between chromosome 14 and 21 or chromosome and segregation
21 and 22 • Alter linkage associations
for the genes contained in
exchanged segments
Disease caused by
translocation
• Chronic myelocytic
leukemia: 22 & 9
Shift translocation • Burkitt’s lymphoma: 8 & 14

Segregation of a chromosome of a translocation heterozygote during meiosis

1. Alternate segregation: opposite or
alternate non-homologous
centromeres go to the same pole in a
zigzag fashion, so that translocated
and non-translocated chromosome
are in separate gametes Anaphase I
2. Adjacent-I segregation:
nonhomologous adjacent
chromosome go the same pole, but
each gamete contains both
translocated and non-translocated
chromosome
3. Adjacent-II segregation: adjacent
centromere again go to the same Anaphase II Anaphase II Anaphase II
pole, but these are now homologous
as well as containing both Gametes: Gametes:
Gametes:
translocated and non-translocated no duplications duplications and duplications and
chromosomes or deficiencies deficiencies deficiencies

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Basic mechanisms for chromosomal rearrangements

Chromosome breakage and rejoining

• Both DNA strands must break at two different locations, followed by a rejoining of broken
ends to produce a new chromosomal rearrangements
• To understand how chromosomal rearrangements are produced by breakage, the following
points must be kept in mind
1. Each chromosome is a single double stranded DNA molecule
2. First event is the generation of two or more double stranded breaks in chromosome of a
cell
3. Double-stranded breaks are potentially lethal, unless they are repaired
4. Repair systems in the cell correct double-stranded breaks by joining broken ends
together
5. If the two ends of the same break are rejoined, the original DNA order is restored. If the
ends of two different breaks are joined together, however, one result is one or another
type of chromosomal rearrangements
6. Chromosomal rearrangements that survive meiosis are those that produce DNA
molecules that have one centromere and two telomere
Acentric chromosome will not be dragged to either pole at anaphase of mitosis or
meiosis and will not be incorporated into either progeny cell

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Dicentric chromosome will often be pulled

simultaneously to opposite poles at anaphase, forming
an anaphase bridge and it will not be incorporated into
either progeny cell
Chromosome lacking telomere due to breakage cannot
replicate properly
7. If a rearrangement duplicates or deletes a segment of a
chromosome, gene balance may be affected
Crossing-over between repetitive DNA segments
• In organisms with repeated short DNA sequences within one
chromosome or on different chromosomes there is ambiguity
about which of the repeats will pair with each other at meiosis
• If sequences pair up that are not in the same relative positions
on the homologs, crossing-over can produce aberrant
chromosomes
• Deletions, duplications, inversion and translocations can all be
produced by such crossing-over

2. NUMERICAL ABERRATION
(changes in chromosome numbers)
• The somatic chromosome number of any species
whether diploid or polyploid is designated as 2n
• The chromosome number of gametes denoted by n
• Gametic chromosome number n is known as
haploid
• A monoploid, on the other hand, has the basic
chromosome number, x Fig: Types of numerical aberrations
• Individuals carrying chromosome numbers other than diploid (2x and not 2n) number are
heteroploids, and situation known as heteroploidy
• The changes in chromosome number may involve one or few chromosomes of the genome,
known as aneuploidy
• The aneuploid changes are determined in relation to the somatic chromosome number (2n
and not 2x) of the species
• Heteroploidy that involves one or more complete genomes is known as euploidy

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Table: Variation in chromosome number

Term Type of change Symbol
Heteroploid A change from 2x
A. Aneuploid One or few chromosome extra or missing from 2n 2n±few
Nullisomic One chromosome pair missing 2n-2
Monosomic One chromosome missing 2n-1
Double monosomic One chromosome from each of two different chromosome pairs missing 2n-1-1
Trisomic One chromosome extra 2n+1
Double Trisomic One chromosome from each of two different chromosome pairs extra 2n+1+1
Tetrasomic One chromosome pair extra 2n+2
B. Euploid Number of genomes or copies of a single genome more or less than two
Monoploid One copy of a single genome x
Haploid Gametic chromosome complement n
Polyploid More than 2 copies of one genome or 2 copies each of 2 or more genomes
1. Autopolyploid Genomes identical with each other
Autotriploid Three copies of one genome 3x
Autotetraploid Four copies of one genome 4x
Autopentaploid Five copies of one genome 5x
Autohexaploid Six copies of one genome 6x
Autooctaploid Eight copies of one genome 8x
2. Allopolyploid Two or more distinct genomes (generally each genome has two copies)
Allotetrapolid Two distinct genomes 2x1 + 2x2
Allohexaploid Three distinct genomes 2x1 + 2x2 + 2x3
Allooctaploid Four distinct genomes 2x1 + 2x2 + 2x3+2x4

ANEUPLOIDY
• Occurs when one or more 4. Translocation heterozygotes: produce (n+1) and
chromosomes of a normal set (genome) (n-1) gametes
are lacking or are present in excess 5. Tetrasomic plants (2n+2): produce (n+1)
• Characterize by incomplete genome gametes
• Monosomics in polyploid species (e.g.
tobacco, wheat) and trisomics in Important points
diploid species (e.g. maize, tomato) are • Aneuploids are generally weaker than diploids
used commonly in genetic studies • Nullisomy is a lethal condition in diploids, but
Origin and production hexaploid can tolerate nullisomy
1. Spontaneous: meiotic irregularities • Monosomics show the deleterious effects of
(non-disjunction) genome imbalance, as well as unexpected
2. Autotriploid plants: irregular expression of recessive alleles carried on the
distribution of chromosome at meiosis monosomic chromosome
I anaphase • Trisomics show the deleterious effects of
3. Asynaptic and Desynaptic mutant: genome imbalance and produce chromosome-
chromosome present as univalent at
metaphase I of meiosis specific modified phenotypic ratios

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Nondisjunction in mitosis or meiosis is the

cause of most aneuploids

Types of Aneuploids
Types of Formula Chromosome Chromosome
aneuploids number and configuration at
complement Diakinesis

Monosomic 2n-1 7: (ABCD)(ABC) 3II+1I

Double 2n-1-1 6: (ABCD)(AB) 2II+2I

monosomic

Nullisomic 2n-2 6: (ABC)(ABC) 3II

Trisomic 2n+1 9: (ABCD)(ABCD)(A) 3II+1III or 4II+1I

Fig. Genotypes of the meiotic products of
Double trisomic 2n+1+1 10: (ABCD)(ABCD)(AB) 2II+2III or 4II+2I an A/a/a trisomic
Tetrasomic 2n+2 10: 3II+1IV or 5II
(ABCD)(ABCD)(A)(A)

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Aneuploidy in human
Types of aneuploids Chromosome composition and Outstanding characteristics
number
a. Sexual aneuploids
Turner’s syndrome 22IIA+XO (2n = 45) Sexual infantilism; mental retardation
Metafemale 22IIA+XXX (2n = 47) Mental retardation; premature menopause
Klinefelter’s syndrome 22IIA+XXY (2n = 47) Underdevelopment in males; sterility; mental
retardation
Double Y-chromosome 22IIA+XYY (2n = 47) Antisocialism; aggressiveness; criminal
tendencies; low I.Q.
b. Autosomal aneuploids
Down’s syndrome 22IIA+I21+XX or XY (2n = 47) Mental retardation; slanting eyes; Mongolian
(Trisomy 21) eyelid fold; saddle nose, swollen tongue
Patau’s syndrome 22IIA+I13+XX or XY (2n = 47) Malformations like harelip and cleft palate;
(Trisomy 13) serious cerebral, ocular and cardiovascular
defects
Edward’s syndrome 22IIA+I18+XX or XY (2n = 47) Malformations in virtually every organ system
(Trisomy 18)

AUTOPOLYPLOIDY
• the multiplication of one basic set of • Triploids (3x): banana, watermelon,
chromosomes i.e. genome doubling sugarbeet, European pear, hyacinths, etc.
• are derived from within a single species • Tetraploids (4x): potato, alfalfa, coffee,
Origin and production peanuts, maize, red clover, etc.
1. Spontaneous: complete non-disjunction
2. Production of adventitious buds:
decapitation leads to callus development
which has some polyploid cells e.g. in
solanaceae
3. Physical agents: X- rays, γ-rays
4. Regeneration in vitro: e.g. callus
culture of Nicotiana, rice
5. Colchicine treatment: doubling
chromosome
6. Crossing between high and low ploidy
level: 4x×2x → 3x

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Triploid
• characteristically sterile
• The problem lies in pairing at
meiosis
• two pairing possibilities,
resulting either in a trivalent or
in a bivalent plus a univalent
• Paired centromeres segregate
to opposite poles, but
unpaired centromeres pass to
either pole randomly
Fig. Two possibilities for the pairing of three homologous
• probability of a meiosis in chromosomes before the first meiotic division in a triploid
which all univalents pass to the
same pole (1/2)x−1 , where x is
number of chromosome Bivalents: Paired chromosomes of the type found in diploids
Trivalents: Associations of three chromosomes and
Univalent: unpaired chromosomes

Tetraploid
• are advantageous as
commercial crops because, in
plants, the larger number of
chromosome sets often leads
to increased size
• can have a regular meiosis
• several pairing possibilities:
the two-bivalent and the
quadrivalent pairing modes
tend to be most regular in
segregation, but even here
there is no guarantee of a 2:2
segregation
Fig. Meiotic paring possibilities in tetrad
• If trivalents form, segregation
leads to nonfunctional
aneuploid gametes and, hence, Quadrivalent: pairing between four chromosomes
sterile

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ALLOPOLYPLOIDY
• the combination of genetically
distinct, but similar chromosome
sets
• arise via hybridization between two
species

Origin and production Allopolyploidy arises from hybridization plus genome duplication
• produced by chromosome
doubling in F1 hybrids between
two distinct species
• chromosome doubling might have
occurred in somatic tissues due to
Fig. Origin and
irregular mitotic cell division or relationships of
due to irregular meiosis leading to different
unreduced gametes polyploids

• Contributed to a greater extent in

evolution of plants
• Evident from wide spread occurrence of
allopolyploids in various genera of plants

Brassica Arachis
Gossypium Nicotiana
Triticum Saccharum
Eleusine Solanum
Avena

• 47% of all angiosperms are polyploids and

in that majority of them are allopolyploids
• About 70% grasses are polyploids
• Extremely rare among sexually
reproducing animals
Fig. Evolution of allohexaploid wheat

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Fig. Evolution of Brassica spp.

Fig. Evolution of allotetraploid cotton

Produced by
G.D. Karpechenko in 1927

Fig. Evolution of allotetraploid tobacco

Fig. Evolution of experimental allotetraploid Raphanobrassica

Table: Variation in chromosome number (basic chromosome number = 4)
Types of polyploid Formula Chromosome complement
Monoploid n (ABCD)
Diploid 2n (ABCD) (ABCD)
Autotriploid 3n (ABCD) (ABCD) (ABCD)
Autotetraploid 4n (ABCD) (ABCD) (ABCD) (ABCD)
Allotetraploid 4n (ABCD) (ABCD) (MNOP) (MNOP)

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Physical Characteristics of Polyploids

Autopolyploids Allopolyploids
• Increased individual cell size, • Are characteristically fertile
although this increase may not extend • Possess many of the physical characteristics of
to tissues and organs autopolyploids
• Responsible for formation of new species, e.g.
• Slower growth rate and later maturity wheat, tobacco, cotton, etc.
than diploids
Table: Chromosome number and plant height in timothy plants
• Thicker leaves, larger and fewer Chromosome Plant Chromosome Plant
flowers and larger fruits than diploids number height (cm) number height (cm)
• Larger stomata size 3n 60 9n 143
4n 79 10n 143
• Reduced fertility in varying degrees 5n 105 11n 117
• Existence, in general, of an optimum 6n 124 12n 85
range of polyploidy beyond which 7n 128 13n 50
growth may be depressed with 8n 135
increasing chromosome number Optimum polyploidy: 6n to 10n

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