04 Nucleic Acids and the RNA World

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    Lectures by Stephanie Scher Pandolfi

    BIOLOGICAL SCIENCE

    FOURTH EDITION

    SCOTT FREEMAN

    4Nucleic Acids and the

    RNA World

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    Key Concepts

    Nucleotides consist of a sugar, phosphate group, and nitrogen-

    containing base. Ribonucleotides polymerize to form RNA.

    Deoxyribonucleotides polymerize to form DNA.

    DNAs primary structure consists of a sequence of nitrogen-

    containing bases; its secondary structure consists of two DNA

    strands running in opposite directions, held together by

    complementary base pairing, and twisted into a double helix.

    DNAs structure allows organisms to store and replicate the

    information needed to grow and reproduce.

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    Key Concepts

    RNAs primary structure consists of a sequence of nitrogen-

    containing bases. Its secondary structure includes short regions of

    double helices and structures called hairpins.

    RNA was likely the first self-replicating molecule and a

    forerunner to the first life-form.

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    What Is a Nucleic Acid?

    A nucleic acid is a polymer ofnucleotide monomers.

    Nucleotides are each composed of a phosphate group, a sugar, and

    a nitrogenous base.

    The sugar is ribosein ribonucleotides and deoxyribosein

    deoxyribonucleotides.

    There are two groups of nitrogenous bases:

    purines (adenine, guanine)

    pyrimidines (cytosine, uracil, and thymine)

    Uracil (U) is found only in ribonucleotides, and thymine (T) is

    found only in deoxyribonucleotides.

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    Could Chemical Evolution Produce Nucleotides?

    Simulations of chemical evolution have not yet produced

    nucleotides.

    Sugars and purines are easily made, but pyrimidines and ribose are

    not easily synthesized.

    Ribose problem: Ribose would have had to have been dominant on

    ancient Earth for nucleic acids to form.

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    Nucleotides Polymerize to Form Nucleic Acids

    Nucleic acids form when nucleotides polymerize.

    A condensation reaction forms a phosphodiester linkage

    (phosphodiester bond)between the phosphate group on the 5

    carbon of one nucleotide and theOH group on the 3 carbon of

    another.

    Types of nucleotides involved:

    1. Ribonucleotides, which contain the sugar ribose and

    form RNA2. Deoxyribonucleotides, whichcontain the sugar deoxyribose

    andform DNA

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    The Sugar-Phosphate Backbone Is Directional

    The sugar-phosphate backbone of a nucleic acid is directionalone

    end has an unlinked 5 carbon, and the other end has an unlinked 3

    carbon.

    The nucleotide sequence is written in the 5 3 direction. This

    reflects the sequence in which nucleotides are added to a growing

    molecule.

    This nucleotide sequence comprises the nucleic acids primary

    structure.

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    The Polymerization of Nucleic Acids Is Endergonic

    Polymerization of nucleic acids is an endergonic process catalyzed

    by enzymes.

    Energy for polymerization comes from the phosphorylation of the

    nucleotides.

    Phosphorylation is the transfer of one or more phosphate

    groups to a substrate molecule. This raises the potential energy

    of the substrate and enables endergonic reactions.

    In nucleic acid polymerization, two phosphates are transferred,

    creating a nucleoside triphosphate.

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    What Is the Nature of DNA's Secondary Structure?

    Erwin Chargaff established two empirical rules for DNA:

    1. The total number of purines and pyrimidines is the same.2. The numbers of As and Ts are equal and the numbers of Cs

    and Gs are equal.

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    Watson and Cricks Model of DNAs Secondary Structure

    James Watson and Francis Crick determined:

    1. DNA strands run in an antiparallelconfiguration.2. DNA strands form a double helix.

    The hydrophilic sugar-phosphate backbone faces the

    exterior.

    Nitrogenous base pairs face the interior.3. Purines always pair with pyrimidines.

    Specifically, strands form complementarybasepairs A-

    T and G-C.

    A-T have two hydrogen bonds. C-G have three hydrogen bonds.

    4. DNA has two different sized grooves: the major groove and

    the minor groove.

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    The DNA Double Helix

    BLAST Animation: DNA Double Helix

    http://localhost/var/www/apps/conversion/tmp/scratch_11/DNA_double_helix.html
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    Structure of RNA and DNA

    Web Activity: Structure of RNA and DNA

    http://localhost/var/www/apps/conversion/tmp/scratch_11/StructureOfRNAandDNA.html
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    Hydrogen Bonds in DNA

    Web Activity: DNA Hydrogen Bonds

    S f A S S

    http://localhost/var/www/apps/conversion/tmp/scratch_11/Hydrogen_bonds_DNA.html
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    Summary of DNAs Secondary Structure

    DNAs secondary structure consists of two antiparallel strands

    twisted into a double helix. The molecule is stabilized by

    hydrophobic interactions in its interior and by hydrogen bonding

    between the complementary base pairs A-T and G-C.

    DNA C i Bi l i l I f i

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    DNA Contains Biological Information

    DNA can store and transmit biological information.

    The language of nucleic acids is contained in the sequence of the

    bases.

    DNA carries the information required for the growth andreproduction of all cells.

    H D DNA R li ?

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    How Does DNA Replicate?

    Complementary base pairing provides a simple mechanism for

    DNA replicationeach strand can serve as a template for the

    formation of a new complementary strand.

    DNA replication requires two steps:

    1. Separation of the double helix

    2. Hydrogen bonding of deoxyribonucleotides with

    complementary bases on the original templatestrand,

    followed by phosphodiester bond formation to form the

    complementarystrand

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    I DNA C t l ti M l l ?

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    Is DNA a Catalytic Molecule?

    DNAs stability makes it a reliable store for genetic information it

    is less reactive than RNA but more resistant to chemical

    degradation. Stable molecules such as DNA make poor catalysts.

    Because DNA does not appear to be able to catalyze any chemical

    reaction, biologists think that the first life-form was made of RNA,

    not DNA.

    RNA St t d F ti

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    RNA Structure and Function

    Like DNA, RNA has a primary structure consisting of a sugar-

    phosphate backbone formed by phosphodiester linkages and,

    extending from that backbone, a sequence of four types of

    nitrogenous bases.

    The primary structure of RNA differs from DNA in two ways:

    1. RNA contains uracil instead of thymine.

    2. RNA contains ribose instead of deoxyribose.

    The presence of theOH group on ribose makes RNA much

    more reactive and less stable than DNA.

    RNA S d St t

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    RNAs Secondary Structure

    RNAs secondary structure results from complementary base

    pairing.

    The bases of RNA typically form hydrogen bonds with

    complementary bases on thesame strand.

    The RNA strand folds over, forming a hairpin structure: the

    bases on one side of the fold align with an antiparallel RNA

    segment on the other side of the fold.

    RNA molecules can have tertiary and quaternary structures.

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    Differences Bet een DNA and RNA

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    Differences Between DNA and RNA

    BLAST Animation: DNA Versus RNA

    RNAs Versatility

    http://localhost/var/www/apps/conversion/tmp/scratch_11/DNA_versus_RNA.html
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    RNAs Versatility

    RNA is structurally, chemically, and functionally intermediate

    between DNA and proteins.

    Like DNA, RNA can function as an information-containing

    molecule, and is capable of self-replication.

    RNA can function as a catalytic molecule.

    Ribozymes are enzyme-like RNAs.

    The First Life Form: RNA

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    The First Life-Form: RNA

    RNA can both provide a template for copying itself and catalyze

    the polymerization reactions that would link monomers into a

    copy of that template. Thus, most origin-of-life researcherspropose that the first life-form was made of RNA.

    RNA is not very stable, but might have survived long enough in

    the prebiotic soup to replicate itself, becoming the first life-form.

    Researchers found that a ribozyme called RNA replicase could be

    isolated that could catalyze the addition of ribonucleotides to a

    complementary RNA strand.