Biology: Molecular Biology of the Gene Chapter 16 PDF

Chapter 16 2 Nucleic Acids Molecular and Inheritance Biology of the Gene...

Chapter 16 2 Nucleic Acids Molecular and Inheritance Biology of the Gene Part 1 Lecture Presentations by Nicole Tunbridge and © 2021 Pearson Education Ltd. Kathleen Fitzpatrick Figure 16.1a © 2021 Pearson Education Ltd. CONCEPT 12.1: DNA is the genetic material The Search for the Genetic Material: Scientific Inquiry When T. H. Morgan’s group showed that genes are located on chromosomes, the two components of chromosomes—DNA and protein—became candidates for the genetic material The role of DNA in heredity was first discovered by studying bacteria and the viruses that infect them © 2021 Pearson Education Ltd. Evidence That DNA Can Transform Bacteria The discovery of the genetic role of DNA began with research by Frederick Griffith in 1928 Griffith worked with two strains of a bacterium, one pathogenic and one harmless When he mixed heat-killed remains of the pathogenic strain with living cells of the harmless strain, some living cells became pathogenic He called this phenomenon transformation, now defined as a change in genotype and phenotype due to assimilation of foreign DNA © 2021 Pearson Education Ltd. Figure 16.2 © 2021 Pearson Education Ltd.  Later work by Oswald Avery, Maclyn McCarty, and Colin MacLeod identified the transforming substance as DNA Many biologists remained skeptical, mainly because little was known about DNA © 2021 Pearson Education Ltd. Evidence That Viral DNA Can Program Cells More evidence for DNA as the genetic material came from studies of viruses that infect bacteria Such viruses are called bacteriophages (or phages) A virus is DNA (sometimes RNA) enclosed by a protective coat, often simply protein Phages have been widely used as tools by researchers in molecular genetics © 2021 Pearson Education Ltd. Animation: Phage T2 Reproductive Cycle © 2021 Pearson Education Ltd.  In 1952, Alfred Hershey and Martha Chase showed that DNA is the genetic material of a phage known as T2 They designed an experiment showing that only one of the two components of T2 (DNA or protein) enters an E. coli cell during infection They concluded that the injected DNA of the phage provides the genetic information © 2021 Pearson Education Ltd. Figure 16.4 © 2021 Pearson Education Ltd. Animation: The Hershey-Chase Experiment © 2021 Pearson Education Ltd. Additional Evidence That DNA Is the Genetic Material DNA is a polymer of nucleotides, each consisting of a nitrogenous base, a sugar, and a phosphate group The nitrogenous bases can be adenine (A), thymine (T), guanine (G), or cytosine (C) In 1950, Erwin Chargaff reported that DNA composition varies from one species to the next This evidence of molecular diversity among organisms made DNA a more credible candidate for the genetic material © 2021 Pearson Education Ltd.  Two findings became known as Chargaff’s rules – The base composition of DNA varies between species – In any species the number of A and T bases is equal and the number of G and C bases is equal The basis for these rules was not understood until the discovery of the double helix © 2021 Pearson Education Ltd. Figure 16.5 © 2021 Pearson Education Ltd. Animation: DNA and RNA Structure © 2021 Pearson Education Ltd. Building a Structural Model of DNA After DNA was accepted as the genetic material, the challenge was to determine how its structure accounts for its role in inheritance Maurice Wilkins and Rosalind Franklin used a technique called X-ray crystallography to study molecular structure Franklin produced a picture of the DNA molecule using this technique © 2021 Pearson Education Ltd. Figure 16.6 © 2021 Pearson Education Ltd.  Franklin’s X-ray crystallographic images of DNA allowed James Watson to deduce that DNA was helical The X-ray images also enabled Watson to deduce the width of the helix and the spacing of the nitrogenous bases The pattern in the photo suggested that the DNA molecule was made up of two strands, forming a double helix © 2021 Pearson Education Ltd.  Watson and Crick built models of a double helix to conform to the X-rays and chemistry of DNA Franklin had concluded that there were two outer sugar-phosphate backbones, with the nitrogenous bases paired in the molecule’s interior Watson built a model in which the backbones were antiparallel (their subunits run in opposite directions) © 2021 Pearson Education Ltd. Figure 16.7 © 2021 Pearson Education Ltd. Animation: DNA Double Helix © 2021 Pearson Education Ltd.  At first, Watson and Crick thought the bases paired like with like (A with A, and so on), but such pairings did not result in a uniform width Instead, pairing a purine (A or G) with a pyrimidine (C or T) resulted in a uniform width consistent with the X-ray data © 2021 Pearson Education Ltd.  Watson and Crick reasoned that the pairing was more specific, dictated by the base structures They determined that adenine (A) paired only with thymine (T), and guanine (G) paired only with cytosine (C) The Watson-Crick model explains Chargaff’s rules: in any organism the amount of A = T, and the amount of G = C © 2021 Pearson Education Ltd. Figure 16.9 © 2021 Pearson Education Ltd.  CONCEPT 12.2: DNA replication and repair Resemblance of offspring to parents relies on accurate replication of DNA prior to meiosis and its transmission to the next generation Replication prior to mitosis ensures the faithful transmission of genetic information from a parent cell to the two daughter cells Watson and Crick noted that the specific base pairing suggested a possible copying mechanism for genetic material The copying of DNA is called DNA replication © 2021 Pearson Education Ltd. The Basic Principle: Base Pairing to a Template Strand Since the two strands of DNA are complementary, each strand acts as a template for building a new strand in replication This yields two exact replicas of the “parental” molecule © 2021 Pearson Education Ltd. Figure 16.10 © 2021 Pearson Education Ltd.  Watson and Crick’s semiconservative model of replication predicts that when a double helix replicates, each daughter molecule will have one old strand (derived or “conserved” from the parent molecule) and one newly made strand Competing models were the conservative model (the two parent strands rejoin) and the dispersive model (each strand is a mix of old and new) © 2021 Pearson Education Ltd. Figure 16.11 © 2021 Pearson Education Ltd. Figure 16.12 Experiments by Matthew Meselson and Franklin Stahl supported the semiconservative model © 2021 Pearson Education Ltd. DNA Replication: A Closer Look The copying of DNA is remarkable in its speed and accuracy More than a dozen enzymes and other proteins participate in DNA replication Replication in bacteria is best understood, but evidence suggests that the replication process in eukaryotes and prokaryotes is fundamentally similar © 2021 Pearson Education Ltd. Getting Started Replication begins at particular sites called origins of replication, where the two DNA strands are separated, opening up a replication “bubble” A eukaryotic chromosome may have hundreds or even thousands of origins of replication Replication proceeds in both directions from each origin, until the entire molecule is copied © 2021 Pearson Education Ltd. Figure 16.13 © 2021 Pearson Education Ltd. Animation: Origins of Replication © 2021 Pearson Education Ltd.  At the end of each replication bubble is a replication fork, a Y-shaped region where parental DNA strands are being unwound Helicases are enzymes that untwist the double helix at the replication forks Single-strand binding proteins bind to and stabilize single-stranded DNA Topoisomerase relieves the strain of twisting of the double helix by breaking, swiveling, and rejoining DNA strands © 2021 Pearson Education Ltd. Figure 16.14 © 2021 Pearson Education Ltd. Synthesizing a New DNA Strand D NA polymerases require a primer to which they can add nucleotides The initial nucleotide chain is a short R NA primer This is synthesized by the enzyme primase The completed primer is five to ten nucleotides long The new D NA strand will start from the 3′ end of the R NA primer © 2021 Pearson Education Ltd.  Enzymes called DNA polymerases catalyze the synthesis of new DNA at a replication fork Most DNA polymerases require a primer and a DNA template strand The rate of elongation is about 500 nucleotides per second in bacteria and 50 per second in human cells © 2021 Pearson Education Ltd.  Each nucleotide that is added to a growing DNA strand is a nucleoside triphosphate dATP supplies adenine to DNA and is similar to the ATP of energy metabolism The difference is in their sugars: dATP has deoxyribose while ATP has ribose As each monomer joins the DNA strand, via a dehydration reaction, it loses two phosphate groups as a molecule of pyrophosphate © 2021 Pearson Education Ltd. Figure 16.15 © 2021 Pearson Education Ltd. Antiparallel Elongation The antiparallel structure of the double helix affects replication DNA polymerases add nucleotides only to the free 3′ end of a growing strand; therefore, a new DNA strand can elongate only in the 5′ → 3′ direction Along one template strand of DNA, the DNA polymerase synthesizes a leading strand continuously, moving toward the replication fork © 2021 Pearson Education Ltd. Figure 16.16 © 2021 Pearson Education Ltd. BioFlix® Animation: Synthesis of the Leading Strand © 2021 Pearson Education Ltd.  To elongate the other new strand, called the lagging strand, DNA polymerase must work in the direction away from the replication fork The lagging strand is synthesized as a series of segments called Okazaki fragments, which are joined together by DNA ligase © 2021 Pearson Education Ltd. Figure 16.17 © 2021 Pearson Education Ltd. BioFlix® Animation: Synthesis of the Lagging Strand © 2021 Pearson Education Ltd. Animation: DNA Replication: An Overview © 2021 Pearson Education Ltd. Animation: DNA Replication Review © 2021 Pearson Education Ltd. Figure 16.18 © 2021 Pearson Education Ltd. Table 16.1 © 2021 Pearson Education Ltd. The DNA Replication Complex The proteins that participate in DNA replication form a large complex, a “DNA replication machine” The DNA replication machine may be stationary during the replication process Recent studies support a model in which DNA polymerase molecules “reel in” parental DNA and extrude newly made daughter DNA molecules The exact mechanism is not yet resolved © 2021 Pearson Education Ltd. Figure 16.19 © 2021 Pearson Education Ltd. Proofreading and Repairing DNA DNA polymerases proofread newly made DNA, replacing any incorrect nucleotides In mismatch repair of DNA, repair enzymes replace incorrectly paired nucleotides that have evaded the proofreading process © 2021 Pearson Education Ltd.  DNA can be damaged by exposure to harmful chemical or physical agents such as cigarette smoke and X-rays; it can also undergo spontaneous changes In nucleotide excision repair, a nuclease cuts out and replaces damaged stretches of DNA © 2021 Pearson Education Ltd. Figure 16.20 © 2021 Pearson Education Ltd. Evolutionary Significance of Altered DNA Nucleotides The error rate after proofreading and repair is low but not zero Sequence changes may become permanent and can be passed on to the next generation These changes (mutations) are the source of the genetic variation upon which natural selection operates and are ultimately responsible for the appearance of new species © 2021 Pearson Education Ltd. Replicating the Ends of DNA Molecules For linear DNA, the usual replication machinery cannot complete the 5′ ends of daughter DNA strands There is no 3′ end of a preexisting polynucleotide for DNA polymerase to add on to Thus, repeated rounds of replication produce shorter DNA molecules with uneven ends This is not a problem for prokaryotes, most of which have circular chromosomes © 2021 Pearson Education Ltd. Figure 16.21 © 2021 Pearson Education Ltd.  Eukaryotic chromosomal DNA molecules have special nucleotide sequences at their ends called telomeres Telomeres do not prevent the shortening of DNA molecules, but they do postpone the erosion of genes near the ends of DNA molecules It has been proposed that the shortening of telomeres is connected to aging © 2021 Pearson Education Ltd. Figure 16.22 © 2021 Pearson Education Ltd.