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

The Modern Era: The Impact of Molecular Biology 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.

Molecular Biology Timeline Lecture no. 2 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

Thomas H. Morgan (1910) discovers genes on chromosomes Lecture no. 2 Thomas H. Morgan (1910) discovers genes on chromosomes Beadle & Tatum (1941) One gene-one enzyme

Avery, Mcleod & McCarty (1944) DNA is genetic material Lecture no. 2 Avery, Mcleod & McCarty (1944) DNA is genetic material 5

Edwin Chargaff (1950) find C complements G and A complements T Lecture no. 2 Edwin Chargaff (1950) find C complements G and A complements T Watson, Crick, Franklin, Wilkins(1953) Structure of DNA 6 6

Brenner, Jacob & Meseleson (1961) Discovery of mRNA Lecture no. 2 Brenner, Jacob & Meseleson (1961) Discovery of mRNA 7 7 7

Central Dogma; Crick & Gamov Lecture no. 2 1956 Central Dogma; Crick & Gamov 1966 Finished unraveling the code; Nirenberg & Khorana 1972 Recombinant DNA made in vitro; P. Berg 1973 DNA cloned on a plasmid; H. Boyer & S. Cohen 1973 Discovery of reverse transcriptase; H. Temin

Rapid DNA sequencing; F. Sanger & W. Gilbert Lecture no. 2 1977 Rapid DNA sequencing; F. Sanger & W. Gilbert 1977 Discovery of split genes; Sharp, Roberts et al. 1982 Discovery of ribozymes; T. Cech & S. Altman 1986 Creation of PCR; K. Mullis et al.

3 Characteristics of “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.

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.

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.

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

Molecular Biology 2000- Present Lecture no.1 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.

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

Nobel Prize Laureates in Physiology or Medicine from 2006 to present Lecture no. 2 Nobel Prize Laureates in Physiology or Medicine from 2006 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

Lecture no. 2 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

For more information please Lecture no. 2 For more information please visit the following link: http://www.dnai.org/timeline/index.html

Lecture no. 2 Homework: Can you identify the most important terms that you have gone through a lecture today and find a scientific definition for it.