RNA Hypothesis

1. Lecture no. 2 RNA Hypothesis

2. Lecture no. 2 Life on Earth Probably Began with RNA • Living systems have definable characteristics and requirements. Catalysis and biological information are particularly important requirements for any life form. • The first molecule that fulfilled the requirements of catalysis and biological information may have been a self-replicating RNA, according to the RNA world hypothesis.

3. The RNA World • The RNA world hypothesis was first proposed as a stage in evolution. The hypothesis describes a living system (or set of living systems) based on RNA. • In this system, a variety of RNA enzymes could catalyze all of the reactions needed to synthesize the molecules required for life from simpler molecules available in the environment. • The “RNA organism,” out of equilibrium with its surroundings, would have to be defined by a boundary. RNA is the only currently used macromolecule that is both a carrier of genetic information and an enzyme.

4. Lecture no. 2 Four more-recent lines of evidence have added much breadth and depth to the plausibility of the proposal • The first was the discovery (early 1980s) of catalytic RNAs, or ribozymes- enzymes that are made of RNA instead of protein. • The second and third discoveries that in ribosomes, the large ribonucleoprotein complexes that translate RNA into protein, the RNA is the active component with the capacity to catalyze protein synthesis. • Another supportive research demonstrated that artificially constructed RNA molecules can catalyze almost any imaginable reaction needed in a living system. • Finally, and most recently, RNA sequences capable of simple forms of self-replication have been discovered.

5. Lecture no. 2 2 1 Rnase P- ribozyme that cleaves tRNA precursors Self-splicing introns Possible remnants of the RNA World 3 4 5 Self-cleaving viral RNAs Peptidyltransferase in the ribosome Nucleotides (ribo) involved in metabolism, Signalling..etc

6. Lecture no. 2 Biochemical Unity Underlies Biological Diversity • LUCA, the last universal common ancestor of all life now present on earth, can be studies by identifying the common characteristics of living organisms and defining the minimal complement of genes necessary to support a living cell. • On the basis of their biochemical characteristics, the diverse organisms of the modern world can be divided into three fundamental groups called domains: Eukarya (eukaryotes), Bacteria, and Archaea . The universal tree of life. A current version of the tree is shown, with branches for the three main groups of known organisms: bacteria, archaea, and eukaryotes.

7. 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.

8. 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

9. Mendel's Laws of Heredity are usually stated as: • The Law of Segregation: Each inherited trait is defined by a gene pair. Parental genes are randomly separated to the sex cells so that sex cells contain only one gene of the pair. Offspring therefore inherit one genetic allele from each parent when sex cells unite in fertilization.

10. Continue… 2) The Law of Independent Assortment: Genes for different traits are sorted separately from one another so that the inheritance of one trait is not dependent on the inheritance of another.

11. Continue… 3) The Law of Dominance: An organism with alternate forms of a gene will express the form that is dominant.

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

13. Lecture no. 2 Avery, Mcleod & McCarty (1944) DNA is genetic material 13

14. Lecture no. 2 Edwin Chargaff (1950) find C complements G and A complements T Watson, Crick, Franklin, Wilkins(1953) Structure of DNA 14 14

15. Lecture no. 2 Brenner, Jacob & Meseleson(1961) Discovery of mRNA 15 15 15

16. 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

17. 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.

18. Lecture no. 2 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.

19. Lecture no. 2 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). http://www.ornl.gov/sci/techresources/Human_Genome/home.shtml

20. Lecture no. 2 Continue… 2003-The Human Genome Project (HGP). Mouse genome is sequenced. 2004- Rat genome sequenced. 2010- Understanding the function of all genes within their cellular, organismal and evolutionary context of Arabidopsis thaliana 20

21. 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

22. 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

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

24. 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. Remember this will be your next lecture, so be prepared.