Workshop On Recent Advances In Genetics

GENETICS 2009
19 February 2009
th

D. Y. Patil University
Kolhapur

Genetic discoveries
that have led to the award
of the
Nobel Prize
for Medicine/Physiology
1962 - 2008

The study of genetics and its role in causing

human disease is now widely acknowledged as
being among the most exciting and influential
areas of medical research. Since 1962 when
Francis Crick, James Watson and Maurice Wilkins
gained acclaim for their elucidation of the
structure of DNA, the Nobel Prize for Medicine
and/or Physiology has been won on 20 occasions
by scientists working in human and molecular
genetics or related fields.

Nobel prize in Medicine/Physiology

1962

Francis Harry Compton Crick

James Dewey Watson

Maurice Hugh Frederick Wilkins

For their discoveries concerning the molecular

structure of nucleic acids and its significance for
information transfer in living material.

Nobel prize in Medicine/Physiology

1962

WatsonCrick double helix model

for the structure of DNA.

X-ray diffraction pattern of DNA studied by

Wilkins - the spots forming a cross in the center
denote a helical structure. The heavy bands at
the left and right arise from the recurring bases.

Nobel prize in Medicine/Physiology

1965

Franois Jacob

Andr Lwoff

Jacques Monod

For their discoveries concerning genetic control

of enzyme and virus synthesis.

Nobel prize in Medicine/Physiology

1965

Lac operon studied by Jacob, Monod & Lwoff.

A) In the absence of lactose, the lac repressor binds DNA and represses transcription
from the lac operon.
B) Allolactose or another inducer binds to the lac repressor, leading to its dissociation
from DNA and to the production of lac mRNA.

Nobel prize in Medicine/Physiology

1966

Peyton Rous

For his discovery of tumour-inducing viruses.

Nobel prize in Medicine/Physiology

1966
Rous showed that viruses could produce tumors in animals. The first virus he discovered
that produced tumors is now called Rous sarcoma virus (which causes sarcomas in chickens).
Rous conceived for the first time that the change of normal cells to cancer cells was not
sudden, but occurred through several, stepwise changes. In the beginning of this process,
designated by Rous as 'tumour progression', the potential cancer cells are in a 'dormant'
state. Chemical agents, viruses or hormonal stimulation may awaken them to a more
aggressive state.
Subsequently, several viruses have been discovered that are capable of producing tumors
in humans. Some human oncogenic viruses and the tumors they cause are:
Hepatitis B Virus - hepatocellular carcinoma
Hepatitis C Virus - hepatocellular carcinoma
Human Papilloma Viruses papillomas & carcinomas of cervix, anus, penis
EpsteinBarr Virus Burkitt's & Hodgkin's lymphoma, nasopharyngeal carcinoma
Kaposi's Sarcoma Virus Kaposi's sarcoma, body-cavity lymphoma
Human T-Cell Leukemia Virus Type I adult T-cell leukemia

Nobel prize in Medicine/Physiology

1968

Robert W. Holley

Har Gobind Khorana

Marshall W. Nirenberg

For their interpretation of the genetic code and its

function in protein synthesis.

Nobel prize in Medicine/Physiology

1968
Each triplet of bases codes for a single
amino acid.
The genetic code is degenerate,
unambiguous, non-overlapping, without
punctuation, and universal.

Rough endoplasmic reticulum where

translation of the genetic code in mRNA
into proteins takes place.

Nobel prize in Medicine/Physiology

1975

David Baltimore

Renato Dulbecco

Howard Martin Temin

For their discoveries concerning the interaction

between tumour viruses and the genetic material
of the cell.

Nobel prize in Medicine/Physiology

1975
The existence of enzymes called reverse transcriptases (that can transcribe viral RNA
into DNA which can integrate into host genome) in RNA retroviruses (such as HIV the
human immunodeficiency virus) was predicted by Howard Temin in 1962, and the
enzymes were ultimately detected by Temin and, independently, by David Baltimore in
1970. Their discovery aroused much attention as dogma-shaking proof that genetic
information can flow backward from RNA to DNA.

Nobel prize in Medicine/Physiology

1978

Werner Arber

Daniel Nathans

Hamilton O. Smith

For the discovery of restriction enzymes and their

application to problems of molecular genetics.

Nobel prize in Medicine/Physiology

1978
Restriction endonucleases (also called restriction
enzymes) recognize and cleave DNA at specific DNA
sequences (recognition sequences or restriction
sites) to generate a set of smaller fragments.
The diagram shows how restriction endonucleases
can be used to clone DNA.

Nobel prize in Medicine/Physiology

1980

Baruj Benacerraf

Jean Dausset

George D. Snell

For their discoveries concerning genetically

determined structures on the cell surface that
regulate immunological reactions.

Nobel prize in Medicine/Physiology

1980
In humans, the genetically determined cell surface antigens that regulate immunologic
reactions are called histocompatibility antigens, because they were found to be the basis
for rejection of foreign transplanted tissue.
The most important of these is the major histocompatibility complex (MHC) of genes
located on chromosome 6. There are 3 classes of MHC molecules, of which class l
molecules are found on the surface of all nucleated cells, and class ll molecules only on
certain cells of the immune system.

Nobel prize in Medicine/Physiology

1980

A. The human major histocompatibility complex (MHC) of genes on chromosome 6, which form
MHC class I (region A, B & C) , II (region D) & III molecules.
B. Class I (left) & class II (right) MHC molecules.

Nobel prize in Medicine/Physiology

1983

Barbara McClintock

For her discovery of mobile genetic elements.

Nobel prize in Medicine/Physiology

1983
Mobile genetic elements, also known as 'jumping genes', are able to move from chromosome
to chromosome, a process known as DNA transposition, which requires enzymes caled
transposases. These were studied in maize by McClintock.
Mobile genetic elements play an important role in the spread of resistance to antibiotics from
resistant to sensitive strains of bacteria.
Transposition of genes is an important step in the formation of antibodies, where the body,
using a limited number of genes, can form an almost endless number of different antibodies
to foreign substances.

Nobel prize in Medicine/Physiology

1985

Michael S. Brown

Joseph L. Goldstein

For their discoveries concerning the regulation of

cholesterol metabolism.

Nobel prize in Medicine/Physiology

1985

As a result of the elucidation of the pathways of cholesterol metabolism, several groups of

lipid-lowering drugs were later developed, including statins, fibrates, & bile acid binding
resins.

Nobel prize in Medicine/Physiology

1987

Susumu Tonegawa

For his discovery of the genetic principle for

generation of antibody diversity.

Nobel prize in Medicine/Physiology

1987
Although humans have only about
30,000 genes, we can produce billions
of different antibodies so each
different antibody cannot be produced
by a single gene.
Antibodies are produced by
rearrangement & somatic
recombination of portions of V, D & J
regions of genes coding for the two
heavy & one light chain of each
antibody molecule
The intervening regions of the genes
between these segments are removed.

Nobel prize in Medicine/Physiology

1989

J. Michael Bishop

Harold E. Varmus

For their discovery of the cellular origin of

retroviral oncogenes.

Nobel prize in Medicine/Physiology

1989
Bishop & Varmus identified the
specifiic gene in the Rous sarcoma
virus that causes neoplastic
transformation, & found that similar
genes were present in normal cells.
Cellular genes that cause cancer
(oncogenes) are designated cOnc, to
distinguish them from viral oncogenes,
vOnc.

Nobel prize in Medicine/Physiology

1993

Richard J. Roberts

Phillip A. Sharp

For their discoveries of split genes.

Nobel prize in Medicine/Physiology

1993

Roberts and Sharp, in 1977, independently of each other, observed that a gene in higher
organisms could be present in the genetic material as several distinct and separate segments
(exons & introns), resembling a mosaic.
Roberts and Sharp also predicted that a specific genetic mechanism is required to enable split
genes to direct the synthesis of proteins.They proposed that messenger RNA in higher
organisms has to be edited, & called the process splicing, where the introns are removed &
exons linked together.

Nobel prize in Medicine/Physiology

1995

Edward B. Lewis

Christiane Nsslein-Volhard

Eric F. Wieschaus

For their discoveries concerning the genetic

control of early embryonic development.

Nobel prize in Medicine/Physiology

1995
The anteroposterior & dorsoventral body
axes of the embryo are established due to
concentration gradients of products of
various genes expressed in a sequential
manner.
Nsslein-Volhard & Wieschaus studied the
bicoid & nanos proteins in the embryo of the
fruitfly Drosophila melanogaster.

Nobel prize in Medicine/Physiology

1997

Stanley B. Prusiner

For his discovery of Prions - a new biological

principle of infection.

Nobel prize in Medicine/Physiology

1997
Prions are infectious protein particles (without any nucleic acid) which cause misfolding of
host cellular proteins. They are the cause of a group of rapidly progressive fatal
neurodegenerative diseases in humans and other mammals, known as spongiform
encephalopathies (because the brain becomes spongy and full of holes)
Human prion diseases include Creutzfeldt-Jakob disease (CJD), variant Creutzfeldt-Jakob
disease (vCJD), Gerstmann-Straussler-Scheinker syndrome, fatal familial insomnia,
& kuru.

Stained section of a human brain with

spongiform change.

The globular domain of human prion protein

(PrP).

Nobel prize in Medicine/Physiology

1999

Gnter Blobel

For the discovery that proteins have intrinsic

signals that govern their transport and localization
in the cell.

Nobel prize in Medicine/Physiology

1999

Blobel's model of protein targeting to specific cellular compartments. (SRP: signal

recognition particle). Newly synthesized proteins (on ribosomes) have a signal sequence
That guides them to the appropriate subcellular compartment.

Nobel prize in Medicine/Physiology

2000

Arvid Carlsson

Paul Greengard

Eric R. Kandel

For their discoveries concerning signal

transduction in the nervous system.

Nobel prize in Medicine/Physiology

2000

Carlsson proved that dopamine is a

neurotransmitter. He then used
reserpine on animals to deplete
dopamine from presynaptic terminals,
and found that the animals lost their
ability to move. He showed that the
animals regained their ability to move
when he gave them L-DOPA.
Greengard showed what happens
when dopamine and other similar
transmitters stimulate a neuron. He
discovered the mechanism of signal
transduction in the nervous system
by protein kinases when
neurotransmitters bind to receptors on
the postsynaptic membrane.
Kandel showed that formation of
memories in the brain is a function of
neuronal synapses. He elucidated the
mechanism of formation of memories.

Nobel prize in Medicine/Physiology

2001

Leland H. Hartwell

Tim Hunt

Sir Paul M. Nurse

For their discoveries of key regulators of the cell

cycle.

Nobel prize in Medicine/Physiology

2001

Phases of the cell cycle: G1, S, G2, M & G0.

Nobel prize in Medicine/Physiology

2001

Cell cycle regulators: cyclins & cyclin-dependent kinases cause progression through
different phases of the cell cycle.

Nobel prize in Medicine/Physiology

2002

Sydney Brenner

H. Robert Horvitz

John E. Sulston

For their discoveries concerning genetic

regulation of organ development and
programmed cell death.

Nobel prize in Medicine/Physiology

2002

Steps in programmed cell death & the genes involved.

Nobel prize in Medicine/Physiology

2006

Andrew Z. Fire

Craig C. Mello

For their discovery of RNA interference - gene

silencing by double-stranded RNA.

Nobel prize in Medicine/Physiology

2006
RNA interference (RNAi).
Exogenous double-stranded RNAs
(dsRNA) or endogenous short hairpin
RNAs (shRNA) are cleaved by the
enzyme dicer into small interfering RNAs
(siRNA), which are unwound by a
helicase into single strands.
One (antisense) strand of siRNA binds to
& activates RISC (RNA-induced silencing
complex).
RISCs bind to & cleave mRNAs in a
sequence-specific manner, thus silencing
specific genes by preventing their
translation.
RNAi has broad therapeutic applications,
from treatment of cancers, to viral
infections such as HIV, & neurodegenerative disorders like Huntington's disease.

Nobel prize in Medicine/Physiology

2007

Mario R. Capecchi

Sir Martin J. Evans

Oliver Smithies

For their discoveries of principles for introducing

specific gene modifications in mice by the use of
embryonic stem cells.

Workshop On Recent Advances In Genetics

GENETICS 2009
19 February 2009
th

D. Y. Patil University
Kolhapur