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BIOL 1020 (35)
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Chapter 16

BIOL 1020 Chapter 16: Chapter 16

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Biological Sciences
BIOL 1020
Joy Stacey

Chapter 16 The Molecular Basis of Inheritanc e Lecture Outline Overview: Life’s Operating Instructions • In April 1953, James Watson and Francis Crick shook the scientific world with an elegant double-helical model for the structure of deoxyribonucleic acid, or DNA. • Your genetic endowment is the DNA you inherited from your parents. • Nucleic acids are unique in their ability to direct their own replication. • Tprecise replication of DNA and its transmission from onethe generation to the next. • Ibiochemical, anatomical, physiological, and (to some extent) behavioral traits. Concept 16.1 DNA is the genetic material The search for genetic material led to DNA. • Once T. H. Morgan’s group showed that genes are located on chromosomes, the two constituents of chromosomes—proteins and DNA—were the candidates for the genetic material. • Until the 1940s, the great heterogeneity and specificity of function of proteins seemed to indicate that proteins were the genetic material. • However, this was not consistent with experiments with microorganisms, such as bacteria and viruses. • The discovery of the genetic role of DNA began with research by Frederick Griffith in 1928. • Hpneumonia in mammals.us pneumoniae, a bacterium that causes  One strain, the R strain, was harmless.  The other strain, the S strain, was pathogenic. • Griffith mixed heat-killed S strain with live R strain bacteria and injected this into a mouse.  The mouse died, and he recovered the pathogenic strain from the mouse’s blood. • Griffith called this phenomenon transformation, a phenomenon now defined as a change in genotype and phenotype due to the assimilation of foreign DNA by a cell. • For the next 14 years, scientists tried to identify the transforming substance. • Finally in 1944, Oswald Avery, Maclyn McCarty, and Colin MacLeod announced that the transforming substance was DNA. • Still, many biologists were skeptical.  Proteins were considered better candidates for the genetic material.  There was also a belief that the genes of bacteria could not be similar in composition and function to those of more complex organisms. • Further evidence that DNA was the genetic material was derived from studies that tracked the infection of bacteria by viruses. • Viruses consist of DNA (or sometimes RNA) enclosed by a protective coat of protein.  To replicate, a virus infects a host cell and takes over the cell’s metabolic machinery.  Viruses that specifically attack bacteria are called bacteriophages or just phages. • In 1952, Alfred Hershey and Martha Chase showed that DNA was the genetic material of the phage T2. • The T2 phage, consisting almost entirely of DNA and protein, attacks Escherichia coli (E. coli), a common intestinal bacteria of mammals. • This phage can quickly turn an E. coli cell into a T2-producing factory that releases phages when the cell ruptures. • To determine the source of genetic material in the phage, Hershey and Chase designed an experiment in which they could label protein or DNA and then track which entered the E. coli cell during infection.  They grew one batch of T2 phage in the presence of radioactive sulfur, marking the proteins but not DNA.  They grew another batch in the presence of radioactive phosphorus, marking the DNA but not proteins.  They allowed each batch to infect separate E. coli cultures.  Shortly after the onset of infection, they spun the cultured that remained outside the bacteria.g loose any parts of the phage  The mixtures were spun in a centrifuge, which separated the heavier bacterial cells in the pellet from lighter free phages and parts of phage in the liquid supernatant.  They then tested the pellet and supernatant of the separate treatments for the presence of radioactivity. • Hershey and Chase found that when the bacteria had been infected with T2 phages that contained radiolabeled proteins, most of the radioactivity was in the supernatant that contained phage particles, not in the pellet with the bacteria. • When they examined the bacterial cultures with T2 phage that had the bacteria.DNA, most of the radioactivity was in the pellet with • Hershey and Chase concluded that the injected DNA of the phage produce new viral DNA and proteins to assemble into new viruses. • The fact that cells double the amount of DNA in a cell prior to provided some circumstantial evidence that DNA was the geneticell material in eukaryotes. • Sdiploid sets of chromosomes have twice as much DNA as thethat haploid sets in gametes of the same organism. • Ba survey of DNA composition in organisms.ries of rules based on  He already knew that DNA was a polymer of nucleotides consisting of a nitrogenous base, deoxyribose, and a phosphate group.  The bases could be adenine (A), thymine (T), guanine (G), or cytosine (C). • Chargaff noted that the DNA composition varies from species to species. • In any one species, the four bases are found in characteristic, but not necessarily equal, ratios. • Hthat are known as Chargaff’s rules.in the ratios of nucleotide bases • In all organisms, the number of adenines was approximately equal to the number of thymines (%T = %A). • The number of guanines was approximately equal to the number of cytosines (%G = %C). • Human DNA is 30.9% adenine, 29.4% thymine, 19.9% guanine, and 19.8% cytosine. • The basis for these rules remained unexplained until the discovery of the double helix. Watson and Crick discovered the double helix by building models to conform to X-ray data. • By the beginnings of the 1950s, the race was on to move from the structure of a single DNA strand to the three-dimensional structure of DNA.  Among the scientists working on the problem were Linus Pauling in California and Maurice Wilkins and Rosalind Franklin in London. • Maurice Wilkins and Rosalind Franklin used X-ray crystallography to study the structure of DNA.  In this technique, X-rays are diffracted as they passed through aligned fibers of purified DNA.  The diffraction pattern can be used to deduce the three- dimensional shape of molecules. • James Watson learned from their research that DNA was helical in nitrogenous bases.ced the width of the helix and the spacing of  Tstrands, contrary to a three-stranded model that Linus Pauling had recently proposed. • Wof DNA with two strands, the double helix.n to work on a model • Using molecular models made of wire, they placed the sugar- inside of the double helix.side and the nitrogenous bases on the  This arrangement put the relatively hydrophobic nitrogenous bases in the molecule’s interior. • Tof a rope ladder.e chains of each strand are like the side ropes  Pairs of nitrogenous bases, one from each strand, form rungs.  The ladder forms a twist every ten bases. • The nitrogenous bases are paired in specific combinations: adenine with thymine and guanine with cytosine. • Pairing like nucleotides did not fit the uniform diameter indicated by the X-ray data.  A purine-purine pair is too wide, and a pyrimidine-pyrimidine pairing is too short.  Only a pyrimidine-purine pairing produces the 2-nm diameter indicated by the X-ray data. • In addition, Watson and Crick determined that chemical side groups of the nitrogenous bases would form hydrogen bonds, connecting the two strands.  Bhydrogen bonds only with thymine, and guanine would formwo three hydrogen bonds only with cytosine.  This finding explained Chargaff’s rules. • Tbases that form the “rungs” of DNA.ombinations of nitrogenous • However, this does not restrict the sequence of nucleotides along each DNA strand. • The linear sequence of the four bases can be varied in countless ways. • Each gene has a unique order of nitrogenous bases. • In April 1953, Watson and Crick published a succinct, one-page paper in Nature reporting their double helix model of DNA. Concept 16.2 Many proteins work together in DNA replication and repair • The specific pairing of nitrogenous bases in DNA was the flash of inspiration that led Watson and Crick to the correct double helix. • The possible mechanism for the next step, the accurate replication of DNA, was clear to Watson and Crick from their double helix model. During DNA replication, base pairing enables existing DNA strands to serve as templates for new complementary strands. • In a second paper, Watson and Crick published their hypothesis for how DNA replicates.  Eother, each can form a template when separated.y to the  Tcomplementary bases and therefore duplicate the pairs of bases exactly. • When a cell copies a DNA molecule, each strand serves as a strand.e for ordering nucleotides into a new complementary  Oaccording to the base-pairing rules.ong the template strand  The nucleotides are linked to form new strands. • Watson and Crick’s model, semiconservative replication, predicts that when a double helix replicates, each of the daughter molecules will have one old strand and one newly made strand. • Other competing models, the conservative model and the dispersive model, were also proposed. • Experiments in the late 1950s by Matthew Meselson and Franklin Stahl supported the semiconservative model proposed by Watson and Crick over the other two models.  In their experiments, they labeled the nucle15ides of the old strands with a heavy isotope of nitrogen ( N), wh14e any new nucleotides were indicated by a lighter isotope ( N).  Replicated strands could be separated by density in a centrifuge.  Each model—the semiconservative model, the conservative model, and the dispersive model—made specific predictions about the density of replic14ed DNA strands.  The first15ep14cation in the N medium produced a band of hybrid ( N- N) DNA, eliminating the conservative model.  Aeliminating the dispersive model and supporting theDNA, semiconservative model. A large team of enzymes and other proteins carries out DNA replication. • It takes E. coli 25 minutes to copy each of the 5 million base pairs in its single chromosome and divide to form two identical daughter cells. • A human cell can copy its 6 billion base pairs and divide into daughter cells in only a few hours. • This process is remarkably accurate, with only one error per ten billion nucleotides. • More than a dozen enzymes and other proteins participat
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