Historical developments

of Molecular Biology

INSTRUCTOR: DR. NEERU REDHU

ASSISTANT PROFESSOR,
COB, CCS HAU
 Molecular Biology - Definition
• Molecular biology is the study of biology at a molecular
level.
• Molecular biology represents the intersection of genetics,
biochemistry, cell biology, Microbiology, virology and
structural chemistry.
• Provides an idea of physical and chemical explanations of life
Molecular Biology Interdisciplinary Science
Molecular biology chiefly concerns itself with understanding
the interactions between the various systems of a cell,
including the interactions between DNA, RNA and protein
biosynthesis as well as learning how these interactions are
regulated
 Beginning of Molecular Biology
Warren Weaver
• The Modern of molecular biology begins in the 1930s with the
convergence of various, previously distinct biological disciplines:
biochemistry, genetics, microbiology, and virology with the hope of
understanding life at its most fundamental level
• Numerous physicists and chemists also took an interest in what would
become molecular biology.
• While molecular biology was established in the 1930s, the term was first
coined by Warren Weaver in 1938. Warren was the director of Natural
Sciences for the Rockefeller Foundation.
 Aims of Molecular Biology
• Molecular biology attempts to explain the phenomena of life starting from the
macromolecular properties that generate them.
• Molecular Biology = molecules of biology; small molecules and macromolecules
• Two categories of macromolecules in particular are the focus of the molecular
biologist:
• Nucleic acids
• Proteins
• To characterize the structure, function and relationships
between these two types of macromolecules
 Before 1930s
• Microscopic biology began in 1665 with the discovery of cells by Robert Hooke (1635-
1703) Robert Hooke
• Matthias Schleiden (1804-1881) and Theodor Schwann (1810-1882) further expanded the
study of cells in 1830s and founded the Cell Theory
• 1865, Gregor Mendel ,father of Genetics discovered the basic rules of heredity of garden
pea.
• An individual organism has two alternative heredity units for a given trait (dominant
trait vs. recessive trait Matthias Schleiden
• 1881 Edward Zacharias showed that chromosomes are composed of nuclein.
• 1899 Richard Altmann renamed nuclein to nucleic acid.
By 1900, chemical structures of all 20 amino acids had been identified

Theodor Schwann
Gregor Mendel
Before 1930s
 1902 - Emil Hermann Fischer wins Nobel prize
 Showed amino acids are linked and form proteins
 Postulated: protein properties are defined by amino acid composition and arrangement,
which we now a days know as a fact Emil Hermann
Fischer

 Mendelian-chromosome theory of heredity came in the 1910s

 1911
 Thomas Hunt Morgan discovers that genes on chromosomes are the discrete units of heredity
 Pheobus Aaron Theodore Lerene discovers RNA

 1928 Frederick Griffith demonstrates a heritable “transforming principle” that transmits Thomas Hunt
the ability of bacteria to cause pneumonia in mice Morgan
 Pheobus Aaron Theodore Lerene characterized DNA and RNA and discovers ribose in
1909 and deoxyribose in 1929
Pheobus Aaron
Theodore Lerene
 After 1930s
 1941 – George Beadle and Edward Tatum identify that genes make proteins
 1944 - Owald Avery, Colin MacLeod, and Maclyn McCarty demonstrated that
Griffith’s bacterial transforming principle is not protein but DNA and suggest that it
may function as the genetic material
 1950 – Edwin Chargaff find C complements G and A complements T
 1950s – Mahlon Bush Hoagland first to isolate tRNA

Edward Tatum

Mahlon Bush Hoagland Edwin Chargaff George Beadle

 1951 Pauling and Corey propose the structure for the alpha helix and beta-
sheet in proteins
 1952
 Alfred Hershey and Martha Chase use bacteriophage (viruses) to confirm that DNA is
the hereditary material
 Maurice Wilkins and Rosalind Franklin use X-ray crystallography to reveal the
repeating structure of B-form of DNA (using DNA purified by Signer)

 1953 Watson and Crick proposed the double helix model for DNA based on x-
ray data obtained by Franklin and Wilkins (Nature, 171:737-738, 1953)
 1955 The sequence of the first protein was analyzed (bovine insulin) by F.
Sanger
 1958 Matthew Meselson and Franklin W. Stahl determined that the mode of
replication was semiconservative.
 The semiconservative method of replication was visually verified by J. Cairns in
1963 using the technique of autoradiography
 1961 Francois Jacob, and Jacques Monod discovered the regulator genes (operons), so called
because they control the activities of structural genes in bacteria. (1965 Nobel Prize)

 In 1955, Severa Ochoa isolated RNA polymerase and made the first synthetic RNA molecules.
Francois Jacob
Later, Nirenberg and Khorana took the lead in deciphering the genetic code and cracked it in
1966.
 1968 Har Gobind Khorana, and Marshall Nirenberg, Nobel Prize for cracking the genetic
code

 1958, John C. Kendrew produced a three-dimensional image/model of myoglobin protein.

(Nobel prize in 1962)
 1965 Robert Holley determined structure of Transfer RNA structure (Nobel Prize in 1968)
Joan Steitz
 1977
 Phillip Sharp and Richard Roberts demonstrated that pre-mRNA is processed by the excision of Richard Roberts
introns and exons are spliced together.
 Joan Steitz determined that the 5’ end of snRNA is partially complementary to the consensus
sequence of 5’ splice junctions
Phillip Sharp
 central dogma of molecular
biology
 Molecular biology remained a pure science with few practical applications
until the 1970s, when restriction enzymes were discovered that could cut
and recombine segments of DNA in the chromosomes of certain bacteria.
 The resulting recombinant DNA technology became one of the most active
branches of molecular biology because it allows the manipulation of the
genetic sequences that determine the basic characters of organisms.
 1970 is also the year wherein major paradigm shift-reversal of the central
dogma of molecular biology
1968 Hamilton Smith and Daniel Nathan independently isolated the first restriction enzyme
HindII
1970 Howard Temin and David Baltimore independently discovered reverse transcriptase in
virions of retroviruses
 result was a major paradigm shift-reversal of the central dogma of molecular biology David Baltimore

In 1972, Paul Berg of Stanford University (USA) created the first recombinant DNA molecule.
 Berg used a restriction enzyme to isolate a gene from a human-cancer-causing monkey virus.
 Then, he used ligase to join the section of virus DNA with a molecule of DNA from the
bacterial virus lambda
 Berg realised the risks of his experiment and temporarily terminated it and proposed a one- Howard Temin
year moratorium on recombinant DNA studies while safety issues were addressed before the
recombinant DNA molecule was added to E. Coli
 recombinant DNA techniques, and was awarded the 1980 Nobel Prize in chemistry
 His experiments founded the field of genetic engineering and the modern biotechnology
industry is based on it.

Paul Berg
 1974
 Frederick Sanger develops a DNA sequencing technique
 During experiments to uncover the amino acids in bovin insulin, he developed the
basics of modern sequencing methods
 DNA sequencing was the dideoxy-chain terminating reaction
 Sanger received first Nobel Prize for bovine insulin and Second Nobel Prize for Frederick Sanger
DNA sequencing technique
 Alan Maxam and Walter Gilbert were creating a somewhat different method of
DNA sequencing called the cleavage method and finally proposed it in 1977

 The base for virtually all DNA sequencing was the dideoxy-chain terminating
reaction, developed by Sanger
1980 The first complete gene sequence for
an organism (ϴX174) was published. The
gene consists of 5,386 base pairs which code
nine proteins.
dideoxy-chain terminating
cleavage method
  1986 Leroy Hood and Lloyd Smith: Developed first semi-automatic DNA sequencer, working
with a laser that recognized fluorescing DNA markers
 1986 Human Genome Initiative announced
 1987
Leroy Hood
 The use of yeast artificial chromosomes (YAC) was described (Burke, et. al., Science, 236:
806-812).
 The physical map of E. coli was published (Kohara, et. al., Cell 51: 319-337).

 1988 The Human Genome Initiative is started (Commission on Life Sciences, National Research
Council. Mapping and Sequencing the Human Genome, National Academy Press: Washington,
D.C.), 1988.
 1990 The 15 year Human
Genome project is launched
by congress

automated sequencing mechanism

 1991 The creation and use of expressed sequence tags (ESTs) is described (J. Craig
Venter, et. al., Science, 252: 1651-1656)
 1995 John Craig Venter: First bacterial genomes sequenced [Haemophilus influenza 1.8
Mb (bacterium that can cause meningitis), Mycoplasma genitalium]
 1996 First eukaryotic (Saccharomyces cerevisiae) genome is sequenced (baker's yeast,
12.1 Mb)
 1997 The genome for E. coli (4.7 Mbp) is published
 1998 Complete sequence of the Caenorhabditis elegans genome
 1999 First human chromosome (number 22) Sequenced
 2000 Caenorhabditis elegans
 The genome for Pseudomonas aeruginosa (6.3 Mbp) is published
 The Arabidopsis thaliana genome (100 Mb) is Sequenced
 Drosophila melanogaster Complete euchromatic genome sequence
was published

Arabidopsis thaliana
 2001 International Human Genome Sequencing: first draft of the sequence of the human genome
published
 2003 Human Genome Project Completed.

 2003 An international sequencing consortium published the full genome sequence of the common
house mouse (2.5 Gb)

 2004 The draft genome sequence of the brown Norway laboratory rat, Rattus norvegicus, was
completed by the Rat Genome Sequencing project Consortium (April 1 edition of Nature)

 The human genome contained 20,000 to 25,000 genes, the cat contains 20,285 genes, the mouse
24,174, and rice 32,000 to 50,000. So in contrast to early assumptions that gene-number correlated
with organismal complexity, it turned out that neither organismal complexity nor even position on the
food chain was predictive of gene-number.
 Year Recipient* Prize Area of Research
2022 Svante Pääbo physiology/medicine discoveries concerning the genomes of extinct hominins and human
evolution
2021 David Julius physiology/medicine discoveries of receptors for temperature and touch

Nobel
Ardem Patapoutian
2020 Harvey J. Alter physiology/medicine discovery of hepatitis C virus
Michael Houghton

Prizes
Charles M. Rice
Emmanuelle Charpentier Chemistry development of a method for genome editing
Jennifer Doudna

concerned
2019 William G. Kaelin, Jr. physiology/medicine discoveries of how cells sense and adapt to oxygen availability
Peter J. Ratcliffe
Gregg L. Semenza

with the
2018 Frances Arnold Chemistry Directed evolution of enzymes and antibodies
George Smith
Gregory Winter

field of
2018 James Allison Physiology Cancer Immunotherapy
Tasuku Honjo
2017 Jacques Dubochet Chemistry Cryo-electron microscopy for high resolution structure determination
Joachim Frank

Molecular 2017
Richard Henderson
Jeffrey Hall
Michael Rosbash
Physiology Mechanism of the circadian rhythm

Biology 2016
2015
Michael Young
Yoshinori Ohsumi
Tomas Lindahl
Physiology
Chemistry
Mechanism of autophagy
Mechanisms of DNA repair
Paul Modrich
Aziz Sancar
2014 Eric Betzig Chemistry Development of super-resolved fluorescence microscopy
W. E. Moerner
Stefan Hell
2013 James E. Rothman Physiology Discoveries of machinery regulating vesicle traffic
Randy W. Schekman
Thomas C. Südhof
 in vivo: studies performed within a living organism

 in vitro: studies performed in cells or tissues grown in culture, or in cell

extracts or synthetic mixtures of cell components
Thank You