Historical perspectives- Early evidence, DNA is the genetic material 1 Lecture no. 2.

Historical perspectives- Early evidence , DNA is the

genetic material

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Lecture no. 2

The Modern Era: The Impact of Molecular The Modern Era: The Impact of Molecular BiologyBiology

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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Molecular Biology TimelineMolecular 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.

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Gregor Mendel’s (Gregor Mendel’s (18651865) Three Laws of ) Three Laws of InheritanceInheritance

Friedrich Miescher (Friedrich Miescher (18691869) identified DNA & called it ) identified DNA & called it nucleinnuclein

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Thomas H. Morgan (Thomas H. Morgan (19101910) discovers genes on ) discovers genes on chromosomeschromosomes

Beadle & TatumBeadle & Tatum ( (19411941) ) One gene-one One gene-one enzymeenzyme

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Avery, Mcleod & McCarty ((19441944) ) DNA is genetic material

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Watson, Crick, Franklin, Wilkins((19531953) ) Structure of DNA

Edwin Chargaff ((19501950) ) find C complements G and A complements T

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Brenner, Jacob & Meseleson ((19611961) ) Discovery of mRNA

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Central Dogma; Crick & Gamov

1956

Recombinant DNA made in vitro; P. Berg

1972

DNA cloned on a plasmid; H. Boyer & S. Cohen

1973

Discovery of reverse transcriptase; H. Temin

1973

Finished unraveling the code; Nirenberg & Khorana

1966

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Rapid DNA sequencing; F. Sanger & W. Gilbert

1977

Discovery of split genes; Sharp, Roberts et al.

1977

Discovery of ribozymes; T. Cech & S. Altman

1982

Creation of PCR; K. Mullis et al.

1986

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3 Characteristics of3 Characteristics of“The Genetic Material”:“The Genetic Material”:

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 materialSearch for genetic material

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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.

Early StudiesEarly Studies

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…

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Phoebus Levene proposed a tetranucleotide structure !! for DNA

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…So…

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

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Molecular Biology 2000- PresentMolecular 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.

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The genome sequence of Drosophila melanogaster.

Science. 287:2185-95. 2000.

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Continue…Continue…

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).

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http://www.ornl.gov/sci/techresources/Human_Genome/home.shtml

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Nobel Prize Laureates in Nobel Prize Laureates in Physiology or Medicine from 2006 Physiology or Medicine from 2006

to present to present

2006 - ANDREW Z. FIRE, and CRAIG C. MELLO for their discovery of RNA interference - gene silencing by double-stranded 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 EraGolden 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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