Transcript BCH361 Historical perspectives-3-2-2014 - Home

Lecture no. 2
Historical perspectivesEarly evidence , DNA is the
genetic material
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Lecture no. 2
The Modern Era: The Impact of Molecular
Biology
 The molecular biology revolution in the middle of the Twentieth
Century provided the means to study the role of genes in
development.
 The key technological advance for the study of gene control of
development was the ability to isolate and clone genes.
 The patterns of expression of individual genes could be
followed by tracing the products of their expression.
 Molecular biology obtained a very powerful tool to facilitate the
study of nucleic acids when the polymerase chain reaction
(PCR) was developed, which amplify specific sequences of DNA
many-fold from a minute amount of starting material.
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Lecture no. 2
Molecular Biology Timeline
 The term molecular biology first appeared in mid 1800s in a report
prepared for the Rockefeller Foundation by Warren Weaver.
 Two studies performed in the 1860s provided the foundation for
molecular biology.
Gregor Mendel’s (1865) Three Laws of Inheritance
Friedrich Miescher (1869) identified DNA & called it nuclein
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Thomas H. Morgan (1910) discovers genes on chromosomes
Beadle & Tatum (1941) One gene-one enzyme
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Avery, Mcleod & McCarty (1944) DNA is genetic material
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Edwin Chargaff (1950) find C complements G and A
complements T
Watson, Crick, Franklin, Wilkins(1953) Structure of DNA
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Brenner, Jacob & Meseleson (1961) Discovery of mRNA
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1956
Central Dogma; Crick & Gamov
1966
Finished unraveling the code; Nirenberg & Khorana
1972
Recombinant DNA made in vitro; P. Berg
1973
1973
DNA cloned on a plasmid; H. Boyer & S. Cohen
Discovery of reverse transcriptase; H. Temin
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1977
1977
1982
1986
Rapid DNA sequencing; F. Sanger & W. Gilbert
Discovery of split genes; Sharp, Roberts et al.
Discovery of ribozymes; T. Cech & S. Altman
Creation of PCR; K. Mullis et al.
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“The Genetic Material”:
Lecture no.2
 Must be a stable form containing information
about cell form and function.
 Must replicate accurately.
 Capable of change to allow evolution..
 Until 1944 it was not known which component of
chromosomes was the genetic material.
 Until 1953 it was not known how DNA could
encode genetic information.
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Search for genetic material
Timeline of events:
• 1890: Weismann - substance in the cell nuclei
controls development.
• 1900: Chromosomes shown to contain hereditary
information, later shown to be composed of protein &
nucleic acids.
• 1928: Griffith’s Transformation Experiment.
• 1944: Avery’s Transformation Experiment.
• 1953: Hershey-Chase Bacteriophage Experiment.
• 1956: First demonstration that RNA is viral genetic
material.
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Early Studies
Lecture no.2
 Beginning with the earliest observations
concerning heredity, genetic material was
assumed to exist.
 Until the 1940s proteins were considered by
geneticists to be the best candidates:
 Very abundant in cells and did nifty things.
 Nucleic acids were similar, and just a couple of
nucleotides connected to each other…
Phoebus Levene
proposed a
tetranucleotide
structure !!for
DNA
Lecture no.2
 He though that a DNA molecule contained only four units, each unit contain
phosphate-sugar-base -in order- linked together in a repeated manner, i.e. a
tetranucleotide.
 Furthermore, he considered such a simple sequence could not allow DNA any role
in coding for anything.
 This was later to be proved wrong by Chargaff.
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So…
Lecture no.2
 It was widely thought that DNA was organized into
repeating "tetranucleotides" in a way that could
not carry genetic information.
 Proteins, on the other hand, had 20 different
amino acids and could have lots of variation.
 Most geneticists focused on “transmission
genetics” and passively accepted proteins as being
the likely genetic material
Lecture no.1
Molecular Biology 2000- Present
2000- The fly Drosophila melanogaster is one of
the most intensively studied organisms in
biology and serves as a model system for the
investigation of many developmental and
cellular
processes
common
to
higher
eukaryotes, including humans. Scientists have
determined the nucleotide sequence of nearly
all
of
the
approximately
120-megabase
euchromatic portion of the Drosophila genome
using a whole-genome shotgun sequencing
strategy.
The genome sequence of
Drosophila melanogaster.
Science. 287:2185-95.
2000.
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Continue…
Lecture no. 2
2001- The Human Genome Project (HGP) began in October 1990 with
a primary goal of determining the sequence of chemical base pairs
which make up DNA, and of identifying and mapping the approximately
20,000–25,000 genes of the human genome from both a physical and
functional standpoint.
Due to widespread international cooperation and advances in the field
of genomics (especially in sequence analysis), as well as major
advances in computing technology, a 'rough draft' of the genome was
finished in 2000 (announced jointly by U.S. President Bill Clinton and
the British Prime Minister Tony Blair on June 26, 2000).
http://www.ornl.gov/sci/techresources/Human_Genome/home.shtml
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Nobel Prize Laureates in
Physiology or Medicine from 2006
to present
Lecture no. 2
 2006 - ANDREW Z. FIRE, and CRAIG C. MELLO for their
discovery of RNA interference - gene silencing by doublestranded RNA.
 2007- MARIO R. CAPECCHI, SIR MARTIN J. EVANS, and
OLIVER SMITHIES for their discoveries of principles for
introducing specific gene modifications in mice by the use of
embryonic stem cells.
 2009- ELIZABETH H. BLACKBURN, CAROL W. GREIDER, and
JACK W. SZOSTAK for the discovery of how chromosomes are
protected by telomeres and the enzyme telomerase
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
We are in the midst of a "Golden Era" of biology,
and the revolution is mostly about treating biology
as an information science, and not only as specific
biochemical technologies
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http://www.dnai.org/timeline/index.html
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Homework:
Can you identify the most
important terms that you have
gone through a lecture today
and find a scientific definition
for it.
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