- The complete OWLS solutions set: OWLSsolutionstoallproblems.pdf OWLSsolutionstoallproblems.pdf - Final review session TODAY led by En-wei in CS24 from 3-4:20pm - Final Exam: - - Each part is worth 100 points and you will have a total of 3 hours to complete both parts (you can work on them in any order you choose, or go back and forth between them). - - Part A will cover all the "new" material since Midterm Part B will be comprehensive and will cover the entire course. Practice on old exams! - Your final exam will be on Wednesday, June 13 from 8-11am. Last name A-C: Please go to Young 2200 Last name D-Z: Please go to CS50 - You may use your model kits! You will be provided with all the information you were given on Midterm 1 and Midterm 2

Biomolecules Survey Part 4: Nucleic Acids Lecture Supplement page 248

Early History 1869: Friedrich Miescher isolates “nuclein” from white blood cells Phosphoric acid Heterocyclic base Heterocycle : Has a least one ring which includes an atom other than carbon Pyrimidines Cytosine (C) Thymine (T) DNA Uracil (U) RNA Purines Adenine (A) Guanine (G) Early 20 th century: Nuclein found to consist of three fundamental componentsX = OH, D -ribose X = H, 2-deoxy- D -ribose

Adenosine (a nucleoside) Nucleosides and Nucleotides 1920’s : Carbohydrate + heterocyclic base = nucleoside Heterocyclic base nitrogen bonded to ribofuranose anomeric carbon Carbohydrate= ribose (X = OH) in ribonucleic acid (RNA) = deoxyribose (X = H) in deoxyribonucleic acid (DNA) Nucleoside + phosphoric acid = nucleotide (nucleoside with phosphate on 3' or 5' carbon) Adenylic acid (a nucleotide) or 1' 2' 3' 4' 5'

DNA is a Polymer 1939: DNA is a polymer of many nucleosides linked by 3', 5'-phosphodiesters 1957 Nobel Prize in Chemistry to Lord Alexander Todd "for his work on nucleotides and nucleotide co-enzymes" (nobelprize.org) Nucleotide sequence = DNA or RNA primary structure (compare protein primary structure)

DNA Carries the Genetic Code Before 1944: Proteins believed to carry genetic information DNA is not much more than a biological curiosity 1944: DNA demonstrated to be the cellular molecule that carries genetic information: Avery, Macleod and McCarty: Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types: Induction of Transformation by a Desoxyribonucleic Acid Fraction Isolated from Pneumococcus Type III, Journal of Experimental Medicine, 1944, 79, After 1944: DNA is the hot topic in biology

Chargaff's Rules 1950's: Erwin Chargaff studies heterocyclic base ratios in DNA from various organisms Chargaff's Rules: In DNA of all organisms... SpeciesGACT(G+A)/(C+T)A/TG/C S. aureus E. coli Wheat germ Bovine thymus Human thymus Human liver Base ratios random in RNA G/C ratio ~1:1 A/T ratio ~1:1 (G+A)/(C+T) = (purines)/(pyrimidines) ratio ~1:1

The Problem Solved 1953: } Not compatible with single helix James Watson and Francis Crick combine... Franklin's x-ray data Chargaff's rules Examination of molecular models } DNA is a base-paired double helix Rosalind Franklin: X-ray studies of DNA show helical structure Diameter = 20 Å Length = 34 Å per 360 o turn Calculated density Watson and Crick made extensive use of models to study molecular structure. Follow their example! Franklin's Photo 51. The X pattern is characteristic of a helical structure = secondary structure of DNA

Watson-Crick Base Pairs Heterocyclic bases associate via two or three hydrogen bonds Adenine-Thymine Guanine-Cytosine Base pairs similar size and shape  efficient packing into double helix same size

Based-Paired Double Helix DNA strands are antiparallel Space-filling model: Atoms represented at their van der Waals radii (electron cloud volumes) Pi stacking 5' end 3' end 3' end 5' end Hydrogen bonds easily disassembled Strong

Based-Paired Double Helix Publication: Watson and Crick, Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Aci d, Nature 1953, 171, "It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material." "We have also been stimulated by a knowledge of the general nature of the unpublished experiment results and ideas of... Dr. R. E. Franklin..." 1962 Nobel Prize in Physiology or Medicine: to Wilkins, Watson, and Crick "for their discoveries concerning the molecular structure of nuclear acids and its significance for information transfer in living material" Optional reading: The Double Helix: A Personal Account of the Discovery of the Structure of DNA (Watson)

The DNA Space Problem Human genome = 3 x 10 9 base pairs (bp) (3 x 10 9 bp) x (34 Å per 10 bp) x ( m per Å) = ~1 meter in length Solution: DNA tertiary structure = supercoiling

Memorize DNA Structure?

CTGGAAGTACGTCTA Leu Glu Val Arg CTAGAAGTACGTCTT

Something Something Alive Something Alive (and complex!) Origin of Universe Origin of Life Variations of Life Nothing