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Overview of milestones in genetics and genetic
variation
Lesson: Overview of milestones in genetics and
genetic variation
Author: Dr. Anjana Singha Naorem
College/Department: Miranda House,
University of Delhi
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Overview of milestones in genetics and genetic
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Table of Contents
 Introduction
 Evolution of Genetics

Mendel’s Work on Transmission of Trait
 Approach
 Experimental Plant: The Garden Pea
 Experiment
 Methodology
 Result
 Inferences drawn by Mendel

Molecular basis of Genetic Information-Historical
Perspectives
 DNA as the Genetic Material
 DNA as a Biomolecule- Composition and Structure
 DNA the Double Helix Structure

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
Genetic Variation
Summary
Exercise
Glossary
References
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Introduction
Genetics is the subject which is centre to humanity in different ways as it has profound
impact on us. It helps us to understand the basic concept of similarities and
dissimilarities between organisms. It is the study of heredity that is how the traits are
passed from generation to generation. This quest for unravelling the secrets behind
transmission of traits from parents to offspring led to the birth of the discipline of
genetics. Though the idea of obtaining desirable traits by cross breeding of animals and
plants was prevalent but the scientific basis for the inheritance was established only in
the 19th century by the work of an Austrian monk, Gregor Johann Mendel (July 20,
1822 – January 6, 1884). His pea plant experiments (1856-1863) led to classical
findings of laws of heredity which is now known as the laws of Mendelian inheritance.
Value addition: Gregor Johann Mendel- Father of Modern Genetics
Heading text: Let’s know him!
Body text:
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Mendel was born Johann Mendel on July 22, 1822 in a town which is today called
Hynice, located in the Czech Republic.
Mendel was a nature enthusiast from birth; he learnt to keep bees at a young age
and was a keen gardener.
His intelligence and aptitude for learning impressed his local school master who
recommended him for higher studies.
Despite financial constraints, he went to high school and excelled in his studies
and graduated with honors in 1840.
After that he enrolled in a two-year program at the Philosophical Institute of the
University of Olmütz where he distinguished himself academically and graduated
in 1843.
In 1843 he joined the Augustinian order at the St. Thomas Monastery in Brno,
and was given the name Gregor, where he trained for priesthood. He was
ordained and for a while taught in a local school.
In 1851 Mendel went to the University of Vienna where he mostly studied physics
before returning to the abbey. Initially, Mendel began his studies on heredity
using mice but due to dislike of his bishop, he switched to plants. It was at the
abbey that Mendel began his famous experiments on peas.
Mendel also bred bees in a bee house that was built for him, using bee hives that
he designed. He also studied astronomy and meteorology, founding the 'Austrian
Meteorological Society' in 1865. The majority of his published works were related
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to meteorology.
Experiments on Plant hybridization
Gregor Mendel was inspired by both his professors at the University of
Olomouc (Friedrich Franz & Johann Karl Nestler) and his colleagues at the monastery
(e.g., Franz Diebl) to study variation in plants, and he conducted his study in the
monastery's 2 hectares (4.9 acres) experimental garden. Between 1856 and 1863 he
conducted several experiments on garden pea which led him to conceptualize what is
today known as Laws of Inheritance.
Source: http://darwin200.christs.cam.ac.uk/pages/index.php?page_id=f4;
http://en.wikipedia.org/wiki/Gregor_Johann_Mendel
Evolution of Genetics
Genetics (from the Ancient Greek word genesis meaning "origin") is the science of
genes, heredity and variation. Genetics though developed during 20th century, it is
rooted by the work of a Moravian monk, Gregor Mendel in the 19th century. Genetics as
a subject have emerged only after the work of Gregor Mendel in the mid 19 th century but
some ideas and theories preceded much before this time. Some of the most common
theories were:

Theory of Pangenesis- The word has a Greek origin pan meaning "whole",
"encompassing" and genesis meaning "birth" or "origin". It was Charles Darwin’s
concept on heredity which held that particles (called pangenes or gemmules)
from all parts of the body come together to form the eggs and sperm (Fig. 1).
This concept was very prevalent until late 1800s. (Figure 1)
Figure 1: Pangenesis
Source: Author
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Inheritance of acquired characters (Jean Baptist Lamarck) means traits
acquired during one’s lifetime is passed on to the next generation. This view
dominated during 20th century. (Figure 2)
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Figure 2: Inheritance of acquired characters
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Source: http://3.bp.blogspot.com/-MoYQsz61xxU/TkfglvKIPI/AAAAAAAAAA8/TYB9ZBtnS7Q/s1600/giraffe_lamark.jpg
(creative commons)
Preformationism: According to this, inside egg or sperm is present tiny adult,
the homunculus, which enlarged during development. Ovist argued that
homunculus resided in the egg and spermists argued it is present in the sperm
implying that traits are passed to the offspring only from one parent. (Figure 3)
Figure 3: The homunculus
Source: https://commons.wikimedia.org/wiki/File:Preformation.GIF
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
Blending inheritance where the offspring was believed to carry the good blend
of parental traits and once the traits are blended they cannot be separated
further. (Figure 4)
Figure 4: Blending inheritance using the color of flowers to
show how a species color variation would converge upon one
color
Source:https://upload.wikimedia.org/wikipedia/commons/thumb/3/32/Bl
ending_inheritance.svg/240px-Blending_inheritance.svg.png
None of these or other theories however, could unravel the mystery of inheritance till
19th century. Geneticist believed that some kind of hereditary material exists in all living
organisms and this material should fulfil three requirements:
 Replication ability-It should be able to replicate so that parents can pass this
material to the offspring
 Information carrier-It must carry necessary information for the animal
development and functioning
 Prone to changes-It should be tenable to change once in a while to account for
variation in the population.
The answer to this mystery came in 1953 when the complete structural elucidation of
DNA was done by James Watson and Francis Crick based X-ray crystallography of DNA
structure given by Rosalind Franklin. A discovery of the hereditary material-DNA! Now
we know that the segments of DNA that codes for a protein is called a gene. It is this
gene which is responsible for inheritance pattern in organisms as well as the variability
that we see in the population. Understanding of this gene and the concepts around it led
to the present day genetics which is studied at various levels-molecular, cellular,
organismal, family, population and at evolutionary level.
This chapter is about the two great milestones in genetics- discovery of concept of
transmission of traits and the identification of the molecule responsible for the basis of
genetic information. The genetic basis of variation is also dealt with in this chapter.
Value addition: A wonder molecule-DNA
Heading text: Discovery of DNA structure
Body text: Middle of the twentieth century is marked by one of the greatest discovery
in the history of mankind-structure of DNA. James Watson (an American molecular
biologist, geneticist and zoologist) and Francis Crick (an English molecular biologist,
biophysicist and neurophysicist) together discovered the double helical structure of DNA
often called a duplex.
Watson and Crick’s double-helix structure was based on findings of many other
scientists. Other researchers had made important but seemingly unconnected findings
about the composition of DNA; it fell to Watson and Crick to unify these disparate
findings into a coherent theory of genetic transfer. The organic chemist Alexander Todd
had determined that the backbone of the DNA molecule contained repeating phosphate
and deoxyribose sugar groups. The biochemist Erwin Chargaff had found that while the
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amount of DNA and of its four types of bases--the purine bases adenine (A) and guanine
(G), and the pyrimidine bases cytosine (C) and thymine (T)--varied widely from species
to species, A and T always appeared in ratios of one-to-one, as did G and C. Maurice
Wilkins and Rosalind Franklin had obtained high-resolution X-ray images of DNA fibers
that suggested a helical, corkscrew-like shape.
Watson and Crick published their findings in a one-page paper, with the understated title
"A Structure for Deoxyribose Nucleic Acid," in the British scientific weekly Nature on April
25, 1953.
In 1962 James Watson, Francis Crick, and Maurice Wilkins jointly received the Nobel Prize in
physiology or medicine for their 1953 determination of the structure of deoxyribonucleic acid
(DNA).
Source: http://profiles.nlm.nih.gov/SC/Views/Exhibit/narrative/doublehelix.html
http://en.wikipedia.org/wiki/DNA
Mendel’s Work on Transmission of Trait
Approach
Mendel’s approach towards the understanding of the concept of inheritance made the
difference the way we look and understand the genetics today. Highlights of Mendel’s
approach are as follows:
 Very scientific and experimentally oriented approach unlike many of the earlier
investigators whose emphasis was only on the results of crosses.
 Formulation of hypotheses- On the basis of his initial observations of the pea
plant he formulated hypotheses which were then tested by performing careful
crosses.
 Chose to study one characteristic at a time,
 True-breeding strains were chosen
 Follow the results of breeding experiments through more than one generation.
 Observed and recorded the result of every crosses carefully
 Subjected the data to statistical analysis.
 Patiently conducted experiments for 8 years
Experimental Plant-The Garden Pea
Of all the different species of plants that Mendel studied he got greatest success with
garden pea. Reason for his success can be attributed to astute selection of the model
plant. Some of the characteristics of the pea plant that attributed to his success are as
follows:
•
•
•
•
•
•
Easy to grow in garden or pots
Grows to maturity in one season
True-breeding plant (plants that produces offspring with the same traits as that of
the parents when the parents were self-fertilized i.e. self-pollinated)
Control over self-pollination possible
Produces large numbers of seeds
Presence of contrasting traits and selecting only these traits
Experiment
Mendel performed his first hybridization experiments with the garden pea in 1856.
Amongst other characters mentioned in the previous section, the closed flowers of the
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garden pea (Figure 5) helped Mendel perform controlled crosses ensuring no crossfertilization on its own. In such closed flowers, the pollen containing the sperm and the
ovules containing eggs are enclosed by two petals fused to form a compartment called a
keel.
Figure: 5. Pisum sativum (Close up of flower showing that
reproductive structures are enclosed in keel)
Source:https://commons.wikimedia.org/wiki/File:Starr_081009-0043_Pisum_sativum_
var._macrocarpum.jpg
Mendel chose seven different contrasting features of the plant which is now referred to
as characters (Figure 6) which were all pure line. Each character possessed two
contrasting properties called the trait. For example, plant height is a character and the
trait would be tall or dwarf. A pure line is a population that breeds true for the particular
character under consideration. That means that the offsprings produced by selfing or
crossing of true breeding lines will produce same trait in the offspring as was present in
the parents.
Figure: 6. Seven contrasting characters of P. sativum that Mendel
studied
Source: http://en.wikipedia.org/wiki/File:Mendel_seven_characters.svg
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Methodology:
1. To get pure line for a trait, different lines of plants for each trait were bred for
continuously two years and that assurred pure line for a trait.
2. To perform the crosses, one character at a time (monohybrid cross) was chosen
initially. Later two characters together (dihybrid cross) were also chosen to
understand the trait transmission. To cross breed the plant he carefully opened
the flowers with scalpel and removed the anthers (emasculated) from one plant
possessing the trait to be studied (example- tall trait) before the pollen maturity
and then brushed the pollen from other plant possessing the contrasting trait (in
this case- dwarf trait), to the stigma of the first plant. The pure bred line chosen
was termed as the parental (P) generation.
3. The resulting seeds were sown the next year getting the hybrid plant uniformly.
Hybrid offspring plants were called the first filial generation (F1 generation)
consisting of only one form of the parental trait and the inheritance pattern was
further studied in the next generation by self-pollinating the F1 plants to obtain
the second filial generation (F2 generation).
4. He very carefully kept the records of all his experiments obtained for different
traits of each characters and a keen analysis of these results led him to formulate
the laws of transmission genetics, the concept of inheritance (which will be dealt
in detail in the subsequent chapters).
Results:
1. In F1 for all the experiments for each character, it was observed that only one
trait was obtained (Table 1).
2. Selfing of F1 generation resulted in getting both the traits again in the second
generation where one trait dominated in number than the other.
3. The trait obtained in abundance in F2 was the one which was observed in F1
generation.
4. All the characters studied showed the similar trend. In F2 generation the traits
were obtained approximately in a ratio of 3:1.
Inferences Drawn by Mendel:
The results of the crosses laid the foundation of the transmission geeticsn. Mendel
concluded that each character occurs in paired form (unit factors) and one of the form
which appears in F1 generation is a dominant trait and the other trait is recessive. The
unit factors separate during gamete formation randomly carrying one of the trait for the
character which combine randomly to form the zygote. Finally concluded and presented
his work in the form of two lectures delivered in German on February 8 and March 8,
1965 to the Natural History Society of Brünn. The results were published in the form
of a paper “Versuche über Pflanzen-Hybriden” in the following year. But his work was not
recognized as being important at that time and went almost unnoticed for almost 35
years. The significance of his work was realized in early 1900s when his work was
rediscovered by Hugo de Vries, Karl Correns, and Erich Tschermak while trying to
understand the results of their plant hybridization experiments. At about the same time,
chromosomal theory of inheritance was proposed by two cytologists, Walter Sutton
and Theodor Boveri, independently linking their discoveries of the behavior of
chromosomes during meiosis to the Mendelian principles of heredity.
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Table 1: Results of Mendel’s monohybrid cross
Character
Seed
Shape
Parental Trait
1. Round×wrinkled
seeds
F1
All round
F2
5474 round; 1850
wrinkled
F2 ratio
2.96:1
Seed
Colour
2. Yellow×green seeds
All yellow
6022 yellow; 2001 green
3.01:1
Flower
Colour
3. Purple×white petals
All purple
705 purple; 224 white
3.15:1
All
inflated
882 inflated; 299 pinched
2.95:1
Pod
Shape
4.
Inflated×pinched
pods
Pod
Colour
5. Green×yellow pods
All green
428 green; 152 yellow
2.82:1
Flower
Position
6. Axial×terminal
flowers
All axial
651 axial; 207 terminal
3.14:1
Plant
height
7. Long×short stems
All long
787 long; 277 short
2.84:1
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Molecular Basis of Genetic Information-Historical Perspective
DNA as the Genetic Material
Though DNA was first described by Friedrich Miescher in 1869 in pus cells and was
initially called as nuclein owing to its extraction from nucleus, but its role in transmitting
genetic information was not anticipated that time. The first work that indicated the
hereditary nature of DNA began with research by Frederick Griffith in 1928 on
Streptococcus pneumoniae, a bacterium that causes pneumonia in mammals. His
experiment demonstrated that heat killed smooth (S) virulent strain of bacteria had the
capacity to transform the live rough (R) non-virulent strain into the virulent form (Figure
7). It took another 14 years to identify the transforming substance. It was in 1944,
Oswald Avery, Maclyn McCarty, and Colin MacLeod identified the transforming substance
to be DNA.
Figure: 7. Griffiths experiment on transformation
Source: http://biowikikoons.wikispaces.com/DNA+Unit+AP+Biology
Convincing evidence of DNA as the genetic material came into light by the experiments
of Alfred Hershey and Martha Chase (1952) on bacteriophage T2. They utilised the
differences in the chemical nature of DNA and protein to ascertain the hereditary
material in T2. They grew separate cultures of T2 in radioactive labelled 32P for DNA and
35
S for protein to infect Escherichia coli. When they examined the bacterial cultures they
found radiolabeled DNA in new virus particles, but no radiolabeled proteins were found
confirming DNA to be the hereditary material (Figure 8).
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Figure: 8. Hershey and Chase Experiment on T2 bacteriophage of E.coli
Source: http://study-biology.wikispaces.com/DNA+and+Genetic+Information
Value addition: Hershey and Chase Experiment
Heading text: DNA as the hereditary material
Body text: Video
Source: http://highered.mcgraw-hill.com/olc/dl/120076/bio21.swf
Value addition: About Hershey and Chase
Heading text: About Hershey and Chase
Body text: Alfred Hershey
Born: December 4th 1908 in Owosso, Michigan
Died: May 22,1997
Profession: He became a bacteriologist and geneticist.
Education and Jobs: He recieved his B.S. in chemistry at Michigan State
University in 1930 and then his Ph.D. in bacteriology four years later.
He
went
on
to
work
at
the
Department
of
Bacteriology
at
the
Washington Univeristy in St. Louis.
Martha Chase:
Born: 1927 in Cleveland, Ohio (nobody seems to know the actual date)
Died: August 8, 2003 (after suffering from dementia and short-term memory loss)
Profession: She was a geneticist.
Education and Jobs: She received her bachelor degree from College of Wooster in
1950. She met and worked with Hershey between her undergraduate and
graduate studies. After working with Hershey, Chase continued to work in Oak Ridge
National Laboratory in Tennessee, University of Rochester, then got her Ph.D. from
University of Southern California.
Together:
DNA Discovery: Chase and Hershey worked together at Carnegie Institution of
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Washington in Cold Spring Harbor, NY. They discovered that DNA was the genetic
information of phages and actually of all living things. They shared a Nobel Prize in
Physiology or Medicines. Although Hershey got almost all the credit then, Chase is now
credited as being his partner.
Chase and Hershey in Cold Spring,
NY during the experiment
Source: http://dnabiob.wikispaces.com/Hershey+and+Chase
DNA as a Biomolecule-Composition and Structure
DNA is a biomolecule which is a storehouse of biological information. Both strands of the
DNA store the same biological information. However, in some organisms RNA
(ribonucleic acids) is the genetic material and stores genetic information. The discovery
of these molecules led to the path-breaking insights into the genetic code and protein
synthesis. Whether DNA or RNA, they are large molecules and are polymers of smaller
similar molecules linked together by covalent bonds. Each unit (monomer) is a
nucleotide which is made up of pentose (five-carbon) sugar, a nitrogenous (nitrogencontaining) base, and a phosphate group. The pentose sugar is deoxyribose in DNA and
ribose in RNA (Figure 9) the two differing in the chemical groups attached to the carbon
number 2: a hydrogen atom (H) in deoxyribose and a hydroxyl group (OH) in ribose.
Figure: 9. Structures of dexoribose and ribose sugar
Source: http://cnx.org/content/m49482/latest/
The two classes of nitrogenous bases are the purines (adenine and guanine), which are
nine-membered, double-ringed structures, and the pyrimidines (cytosine, thymine and
uracil), which are six-membered, single-ringed structures (Figure 10). All the bases are
similar in DNA and RNA except that thymine is found in DNA and uracil in RNA. The
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sugar at carbon 1’ is attached at 9 nitrogen of purine and 1 nitrogen of pyrimidine. The
combination of a sugar and nitrogenous base is called nucleoside. The phosphate group
attachment to the carbon of the sugar makes the entire unit a nucleotide (Figure 11a).
The nucleotides are linked together by a covalent bond between the phosphate group of
one nucleotide and the carbon of the sugar of another nucleotide forming phosphodiester
bonds (Figure 11b). These chains have polarity having carbon with a phosphate group on
it at one end, and a carbon with a hydroxyl group on it at the other end (Figure 11b).
The ends of a polynucleotide are routinely referred to as the 5’ end and the 3’ end.
Figure: 10. Structure of purine and pyrimidine bases
Source: http://cnx.org/content/m49482/latest/
(a)
(b)
Figure: 11. (a) Structure of a DNA nucleotide; (b) A short polynucleotide chain of DNA
Source: iGenetics (This figure also needs modification)
The four bases- adenine (A), thymine (T), guanine (G) and cytosine (C) present in
various sequence combinations in DNA give rise to the amino acid sequences of proteins.
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DNA the Double Helix Structure
After the structural elucidation of DNA by Watson and Crick in 1953, it was shown that
the two strands of DNA are exactly complementary to each other, so that the rungs of
the ladder in the double helix always consist of A pairing up with T and G with C. This
complementarity forms the basis for gene expression meaning expression of phenotype.
Before we understand the genetic expression of a phenotype let us understand the main
feature of Watson and Crick’s double DNA helix structure (Figure 12):
1. DNA molecule consists of two polynucleotide chains wound around each other in a
right-handed fashion
2. The two chains are antiparallel showing polarity meaning one chain if oriented in 5’ to
3’ direction then the other chain is in the 3’ to 5’ direction.
3. The sugar–phosphate forms the backbones with the bases oriented toward the central
axis.
4. The bases in each of the two polynucleotide chains are bonded together by hydrogen
bonds A bonded with T (two hydrogen bonds) and G bonded with C (three hydrogen
bonds). A–T and G–C pairs are called complementary base pairs and they are specific
for each other so the nucleotide sequence in one strand determines the nucleotide
sequence of the other.
Figure: 12. Molecular structure of DNA double helix
Source: http://cnx.org/content/m49482/latest/
5. The base pairs are 0.34 nm apart in the DNA helix. A complete (360°) turn of the
helix takes 3.4 nm which means 10 base pairs (bp) per turn. The external diameter of
the helix is 2 nm.
6. Because of the way the bases bond with each other, the two sugar–phosphate
backbones of the double helix are not equally spaced from one another along the helical
axis. This unequal spacing results in grooves of unequal size between the backbones;
one groove is called the major (wider) groove, the other the minor (narrower) groove.
These characteristics of DNA structure could be determined largely due to the
experimental results of Erwin Chargaff (for base composition- Chargaff’s rule) and
Rosalind Franklin with Maurice H.F. Wilkins (for X-ray diffraction). Base composition
studies revealed that amount of adenine was always equal to thymine and same hold
true for Guanine and cytosine in a double DNA molecule. The amount of purines was also
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found to be equal to the amount of pyrimidines implying that (A+G)/(C+T) ratio is 1.
Also, the A/T ratio and G/C ratio is 1.
These base compositions are varied in different cells and in different organisms. The
process of genetic expression begins in the nucleus with transcription of DNA, in which
the information that resides in the form of nucleotide sequence in one strand of DNA is
used to construct a complementary RNA sequence, called the messenger RNA (mRNA).
mRNA then moves to the cytoplasm for protein synthesis by the process called
translation (Figure 13). mRNA carries the genetic information in the form of nucleotide
triplets in a linear manner. Each triplet is called a codon. The codons carry the encoded
information for specific amino acids. mRNA carrying the encoded information binds with
ribosomes and the transfer RNA (tRNA) carrying the specific amino acid recognizes the
codon in mRNA and construct the amino acid chain following the series of the codons. All
these processes are aided by several enzymes. This flow of information from DNA to RNA
and to protein was formalized by Francis Crick in a concept called central dogma
(Figure 14). According to this concept passage of information from DNA to protein is a
one-way information pathway which implies that genotype codes for phenotype but
phenotype cannot code for genotype. Genes direct the synthesis of wide array of
proteins that collectively serve as the basis for all biological function and generates huge
genetic variation which will be discussed in the next section.
Figure: 13. Generalized view of transcription and translation
Source:http://nnhsbiology.pbworks.com/f/1280666569/transcription%20translation%2
0diagram.png
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Figure: 14. Central dogma
Source: http://openwetware.org/wiki/Image:Icgems_centdog.gif
Genetic Variation
Genetic variation is an outcome of several processes and is seen both within and among
populations. It is an important process from both genetics and evolutionary point of view
as it provides raw material for the natural selection to act upon. Genetic study relies on
all these variations that exist in nature. The various sources of genetic variations are:
1) Randomness in formation of gametes leads to different combination of alleles (an
alternate form of a gene) which on fertilization further contributes towards generating
huge diversity. In diploid organisms, during gamete formation a meiotic event called
crossing over leads to generation of variation in the gametes by reshuffling of genetic
material (Figure 15). Further the random distribution of maternal and paternal
chromosomes during meiosis shuffles alleles on different chromosomes into new
combinations (Figure 16). Sexual reproduction thus leads to variation by means of
recombination of genes during meiosis which then segregate and assort independently in
gametes.
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Figure: 15. Crossing over leading to genetic recombination.
Source: http://semoneapbiofinalexamreview.wikispaces.com/L.+Meiosis+(13)
Figure: 16. The random segregation of chromosome into daughter nuclei that happens
during the first division in meiosis can lead to a variety of possible genetic
arrangements.
Source: http://semoneapbiofinalexamreview.wikispaces.com/L.+Meiosis+(13)
2) In prokaryotes also genetic variation is essential as it confers survival advantage to
them. These variations are introduced by means of genetic exchange processes like
conjugation (Figure 17), transformation and transduction that may take place within
members of the same bacterial species or different species.
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Figure: 17. Diagram of bacterial conjugation. 1- Donor cell produces pilus. 2- Pilus
attaches to recipient cell and brings the two cells together. 3- The mobile plasmid is
nicked and a single strand of DNA is then transferred to the recipient cell. 4- Both cells
synthesize a complementary strand to produce a double stranded circular plasmid and
also reproduce pili; both cells are now viable donors.
Source: http://en.wikipedia.org/wiki/Bacterial_conjugation
3) Mutations, a sudden change in the genetic material of the organism by means of
physical or chemical agents, also induce genetic variation. Such variations include
alterations of chromosome number and rearrangements within and between
chromosomes. Structural differences such as deletions, duplications, inversions, which
may sometimes lead to copy number variations (CNVs) (Figure 18), create genome
variation. CNVs are the structural alterations of the DNA that leads to variations
in the number of copies of one or more regions of the DNA. The mutation can be
used as genetic analysis tool as they act as genetic markers also to identify the gene
responsible for phenotypic alteration. Generation of diversity by mutations are
sometimes associated with certain drawbacks like, cell death, cancer, diseases, etc.
Figure: 18. Gene duplication has created a copy-number variation. The chromosome
after duplication (on right) has two copies of the highlighted gene
Source: http://en.m.wikipedia.org/wiki/File:Gene-duplication.png
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4) Recent advances in the field of molecular biology and biotechnology have revealed
that the variations can also occur due to single nucleotide polymorphisms (SNP,
pronounced snip) (Figure 19). SNP is a DNA sequence variation in which a single
nucleotide in the genome differs between members of a species or paired chromosomes.
Occurring commonly within a population, SNPs are important contributing factors to
genome variation.
Figure: 19. Single nucleotide polymorphism
Source: http://commons.m.wikimedia.org/wiki/File:Dna-SNP.svg
Value addition: What makes every individual organism unique ….?????
Heading text: Mechanisms that increase genetic variation
Body text: Video lecture on genetic variation
Source: http://biocomicals.blogspot.in/2011/03/genetic-variation.html
Source of video: http://www.youtube.com/watch?v=UjMn4oHfYL4
Summary
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Overview of milestones in genetics and genetic
variation
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Genetics is the study of heredity and variation
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His success could be attributed to astute choice of experimental plant which was
short growing cycle, self-fertilized, true breeding, produced large number of
seeds, possessed contrasting trait. His quantitative, methodical approach and
keeping careful records of his observations followed by mathematical analysis of
his results contributed to his success in postulating the laws of heredity.

Though Mendel’s work was not appreciated and given due appreciation in 19 th
century but with the rediscovery of his work in early 20 th century, his
contributions in the field of modern genetics was well recognized and he is now
regarded as the father of genetics.
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In the middle of 19th century an Austrian monk Gregor Johann Mendel’s
experiments with garden pea brought to light the new understanding of concepts
of inheritance called as laws of Mendelian inheritance.
Surprisingly, Mendel postulated all his theories much before the concept of cell
cycle, meiosis and DNA were known.
DNA was first discovered in 1869 by Friedrich Miescher from the pus cells but its
role as a genetic material could be recognized only in middle of 20 th century.
Frederick Griffith’s research (1928) on Streptococcus pneumonia was the first
work that indicated the hereditary nature of DNA but due to the lack of proper
explanation DNA as a hereditary material could not be concluded. Soon the
research by Oswald Avery, Maclyn McCarty, and Colin MacLeod identified the
transforming substance to be DNA in 1944. Confirming evidences were given by
the experiments of Alfred Hershey and Martha Chase (1952) on bacteriophage T2
establishing DNA as the genetic material.
It was only in 20th century (1953) that the structure of DNA was elucidated by
Watson and Crick as a double helical structure comprising chains of nucleotides.
Their study was based on the findings of Maurice Wilkins, Rosalind Franklin, Erwin
Chargaff and many others.
DNA is a polymer of nucleotides. Each nucleotide unit comprises of a sugar,
nitrogenous base (purine or pyrimindine) and a phosphate. Every nucleotide is
joined with the next with a covalent bond between the phosphate group of one
nucleotide and the carbon of the sugar of another nucleotide forming
phosphodiester bonds. The two chains of DNA are antiparallel having sugarphosphate backbone.

Variation in the base composition of DNA strands make variable proteins leading
to the diversity of cells and organisms that we see around us.

During protein synthesis, DNA strands that carry the useful information are first
transcribed into mRNA which are then transported to cytoplasm where they are
translated finally into chains of amino acids as dictated by the mRNA strand using
ribosomes, tRNA and several enzymes. This unidirectional flow of information
from DNA to protein via RNA is called central dogma.

The extent of genetic diversity around us is due to several reasons: crossing over
during meiosis, random segregation of chromosome during meiosis, genetic
exchanges (conjugation, transformation or transduction) between bacteria and
mutation.

Genetic variation is important as it confers survival value to the organism and
act as a raw material for natural selection.
Exercise
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Overview of milestones in genetics and genetic
variation
1. Differentiate between the following:
a) Purine and pyrimidine
b) Nucleoside and nucleotide
c) Codon and amino acid
d) Transcription and translation
e) DNA and RNA
f) Genetic variation and crossing over
g) CNVs and SNP
h) Character and trait
2. Match the names of the scientists with their contribution.
a) Gregor Johann Mendel
1.
Duplex helical DNA
b) James Watson and Francis Crick
2.
X-Ray Crystallography structure of
DNA
c) Erwin Chargaff
3.
Laws of inheritance
d) Alfred Hershey and Martha Chase
4.
Demonstration of DNA as the
genetic material in bacteriophage T2
e) Rosalind Franklin
5.
Base pairing rules
3. How many hydrogen bonds are present in the complementary base pairing
between guanine and cytosine?
a) 2
b) 3
c) 1
d) 4
4. ..................was Frederick Griffith’s experimental subject to demonstrate the
hereditary nature of DNA.
a) Streptococcus pneumonia
b) Escherichia coli
c) T2 bacteriophage
d) Pisum sativum
5. Central dogma is the flow of genetic information from..................
a) RNA to DNA
b) RNA to DNA to protein
c) DNA to RNA to protein
d) Protein to RNA to DNA
6. Transcription takes place in the.................
a) Cytoplasm
b) Nucleus
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Overview of milestones in genetics and genetic
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c) Within the ribosomes in the cytoplasm
d) Within the nucleus in the nucleolus
7. Expand the following abbreviations.
a) CNVs
b) SNP
c) RNA
d) DNA
8. Indentify them.
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Short answer questions
9. What kind of bonding is present between A & T and G & C? Based on its type of
bonding, which one would be difficult to break and why?
10. What do you think was the reason for Mendel’s success?
11. How the garden pea was a good model for the study of inheritance?
12. What are the three key characteristics that a genetic material should possess?
13. How does the concept of the inheritance of acquired traits related to the concept
of pangenesis?
14. Arrange the given melting temperatures of the double stranded DNA in a
decreasing order of the G-C content: Give reason
a) 70oC,
b) 74 oC
c) 83 oC
d)86 oC
e) 80 oC
Long answer questions
15. Explain the experimental evidences that led to the confirmation that DNA is the
genetic material of the living organisms.
16. Explain the double helix model of DNA.
17. What are the factors that generate genetic variation in the population? Explain
Analytical question
18. If a double stranded DNA contains 100 deoxyadenylic acid and 130
deoxyguanylic acid residues, what is the total nucleotide content in the DNA
fragment?
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Overview of milestones in genetics and genetic
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19. A double-stranded DNA molecule is 10,000 bp long. How many nucleotides does
it contain and how long is the DNA molecule in nanometres? How many complete
turns can be found in the fragment?
20. Following is the list of hypothetical relative percentages of nucleic acid bases
from different organisms. Identify the type of nucleic acid (DNA/RNA) in each
species. Is it single or double-stranded? Give reasons.
Species
Adenine
Guanine
Thymine
Cytosine
Uracil
a
30
39
30
39
0
b
21
30
0
30
21
c
30
30
39
39
0
d
32
40
0
32
40
e
39
30
39
30
0
Glossary
Adenine Purine base; one of the four nitrogenous base which combines with
deoxyribose sugar and phosphoric acid to form a nucleotide, the basic unit of DNA and
RNA.
Amino acid A unit constituting the building blocks of protein; consists of an amino
group, a carboxylic group, a hydrogen atom, and a variable R group.
Biomolecule Molecules produced by a living organisms example: proteins, lipids,
carbohydrates, nucleic acids, etc
Central dogma Concept that flow of genetic information is sequential unidirectional
from DNA to RNA to protein.
Chargaff’s rules Formulated by Erwin Chargaff. It states that DNA from any organism
should have a 1:1 ratio of purine and pyrimidine bases i.e., amount of guanine is equal
to cytosine and amount of adenine is equal to thymine.
Codon A group of three adjacent nucleotides in an mRNA molecule that specifies either
one amino acid in a polypeptide chain or the termination of polypeptide synthesis.
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Overview of milestones in genetics and genetic
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Complementary base pairs The specific A-T and G-C base pairs in double-stranded
DNA. The bases are held together by hydrogen bonds between the purine and pyrimidine
base in each pair.
Conjugation In bacteria, process of unidirectional transfer of genetic material through
direct cellular contact between a donor (“male”) cell and a recipient (“female”) cell.
Cross The fusion of male gametes from one individual and female gametes from
another.
Crossing-over The process of reciprocal
chromosomal
interchange
that occurs
frequently during meiosis and gives rise to recombinant chromosomes.
Copy number variation (CNV) Form of structural variation where a section of DNA of
an organism’s genome have been deleted or duplication on certain chromosomes.
Deoxyribonucleotide Basic unit of DNA structure compose of a deoxyribose, a
phosphate and a nitrogenous base.
Deoxyribose Pentose sugar which lacks a hydroxyl group on 2’ carbon atom. It
combines with a nitrogenous base and a phosphate to form a nucleotide, a basic unit of
DNA structure.
F1 generation The offspring that result from the first experimental crossing of two
parental strains of animals or plants; the first filial generation.
F2 generation The offspring that result from crossing individuals; the second filial
generation.
Gamete Mature reproductive cell that is specialized for sexual fusion. Each gamete is
haploid and fuses with a cell of similar origin but of opposite sex to produce a diploid
zygote.
Gene In molecular terms, a gene is a nucleotide sequence in DNA that specifies a
polypeptide or RNA.
Genetic code The set of three-nucleotide sequences (codons) within mRNA that carries
the information for specifying the amino acid sequence of a polypeptide.
Genetics The science that deals with the structure and function of genes and their
transmission from one generation to the next (heredity).
Guanine Purine base; one of the four nitrogenous base which combines with
deoxyribose sugar and phosphoric acid to form a nucleotide, the basic unit of DNA and
RNA.
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Overview of milestones in genetics and genetic
variation
Mutation Any detectable and heritable change in the genetic material not caused by
genetic recombination; mutations may occur within or between genes and are the
ultimate source of all new genetic variation.
Nitrogenous base A nitrogen-containing purine or pyrimidine that, along with a
pentose sugar and a phosphate, is one of the three parts of a nucleotide.
Nucleic acid High-molecular-weight polynucleotide. The main nucleic acids in cells are
DNA and RNA.
Nucleoside A purine or pyrimidine covalently linked to a sugar.
Nucleotide The type of monomeric molecule found in RNA and DNA. Nucleotides consist
of three distinct parts: a pentose (ribose in RNA, deoxyribose in DNA), a nitrogenous
base (a purine or pyrimidine), and a phosphate group.
P generation The parental generation; the immediate parents of F1 offspring.
Pentose sugar A five-carbon sugar that, along with a nitrogenous base and a
phosphate group, is one of the three parts of a nucleotide.
Polynucleotide A linear polymeric molecule composed of nucleotides joined by
phosphodiester bonds. DNA and RNA are polynucleotides.
Pure line A pure line is a population of that breeds true for the particular trait under
consideration.
Purine Heterocyclic aromatic organic compound consisting of a pyrimidine ring fused to
an imidazole ring. It is one of the two groups of nitrogenous bases consisting of adenine
and guanine.
Pyrimidine Heterocyclic aromatic organic compound. It is one of the two groups of
nitrogenous bases consisting of cytosine and thymine.
SNP (single nucleotide polymorphism) Single base-pair alteration in a stretch of
DNA found between individuals that can be used as a DNA marker.
Transcription The process for making a single-stranded RNA molecule complementary
to one strand (the template strand) of a double-stranded DNA molecule, thereby
transferring information from DNA to RNA. Also called RNA synthesis.
Transduction A process by which bacteriophages mediate the transfer of pieces of
bacterial DNA from one bacterium (the donor) to another (the recipient).
Transformation (a) In bacteria, a process in which genetic information is transferred by
means of extracellular pieces of DNA. (b) In eukaryotes, the conversion of a normal cell
with regulated growth properties to a cancer-like cell that can give rise to tumors.
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Overview of milestones in genetics and genetic
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Translation The process that converts the nucleotide sequence of an mRNA into the
amino acid sequence of a polypeptide. Also called protein synthesis.
References
1. Pierce, B.A. (2012). Genetics - A Conceptual Approach. IV Edition. W. H.
Freeman & co. NY.
2. Gardner, E.J., Simmons, M.J. and Snustad, D.P. (2008). Principles of
genetics. Eighth edition. Wiley.
3. Klug, W.S., Cummings, M.R., Spencer, C.A. and Palladino, M.A. (2012).
Concepts of genetics. Tenth edition. Pearson
4. Russel, P.J. 2010. iGenetics A Molecular Approach. Beth Wilbur (ed.) 3rd
Edition. Pearson Education, Inc.
Websites
http://www.dnalc.org/view/16002-Gregor-Mendel-and-pea-plants.html
http://www.mendelweb.org/archive/Mendel.Experiments.html
http://biowikikoons.wikispaces.com/DNA+Unit+AP+Biology
http://www.ncbi.nlm.nih.gov/pubmed/15680349
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