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Molecular Basis for Inheritance Campbell Chapter 16

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Page 1: Molecular Basis for Inheritance - WordPress.com · molecular basis of inheritance O Griffith (1927) Bacteria have the ability to transform harmless cells in to virulent ones by transferring

Molecular Basis for Inheritance

Campbell Chapter 16

Page 2: Molecular Basis for Inheritance - WordPress.com · molecular basis of inheritance O Griffith (1927) Bacteria have the ability to transform harmless cells in to virulent ones by transferring

Discovery of DNA

O To understand genetics discover the

chemical nature of a gene

O Identify the molecule that carries

genetic information understand how

genetics works

O Frederick Griffith (1928) wanted to

know why people got pneumonia but

discovered the chemical nature of a

gene

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Griffith’s ExperimentsO Isolated two different strains of bacteria

O Disease-causing bacteria pneumonia (S strain)

O Harmless bacteria (R-strain)

O Inject mice with S strain developed pneumonia and died

O Inject mice with harmless R-strain stayed healthy

O What killed the mice?

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Griffith’s Next Experiments

O Heated and killed the S-strain cells and injected mice.

Mice survived the cause of pneumonia was not a toxin

from the bacteria

O Mixed the heat-killed, S-strain bacteria with live, harmless

R-strain bacteria and injected mice. Injected mice

developed pneumonia and died

O How could that happen if the S-strain cells were dead?

Harmless

bacteria (R strain)

Page 5: Molecular Basis for Inheritance - WordPress.com · molecular basis of inheritance O Griffith (1927) Bacteria have the ability to transform harmless cells in to virulent ones by transferring

Bacterial TransformationO Somehow the heat-killed bacteria passed their

disease-causing ability to the harmless bacteria

O Transformation – process in which one strain of

bacteria takes as piece of DNA and integrates it in

its genome

O Ability to cause disease was inherited by the

offspring of the transformed bacteria

concluded that the

transforming factor

had to be a gene

Page 6: Molecular Basis for Inheritance - WordPress.com · molecular basis of inheritance O Griffith (1927) Bacteria have the ability to transform harmless cells in to virulent ones by transferring

The Molecular Cause of Transformation

O Which molecule in the heat-killed bacteria was most important for transformation?

O Canadian biologist Oswald Avery and his team destroyed all parts of the bacterium except the DNA transformation still occurred

O repeated the experiment but destroyed DNA transformation did not occur

O by observing bacterial transformation, Avery and other scientist discovered that the nucleic acid DNA stores and and transmits genetic info from one generation to generation

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Bacteriophages

O Bacteriophage - type of virus that

infects bacteria

O When a bacteriophage enters a

bacterium, it attaches to the surface of

the bacterial cell and injects its DNA

into it

O The bacteriophage genes produce

many new bacteriophages, which

gradually destroys and splits open the

bacterium

O Hundreds of new viruses burst out

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The Hershey-Chase ExperimentO American scientists Alfred Hershey and Martha Chase studied

a bacteriophage to determine which part of the bacteriophage—the protein coat or the DNA core—entered the bacterial cell

O Grew viruses containing radioactive isotopes (markers) enabling the scientists to tell if the protein coat or the DNA core carried the genetic information of the virus

O Nearly all the radioactivity in the bacteria was from the marker found in DNA

O DNA stores and transmits genetic information from one generation of bacteria to the generation

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Solving the Structure of DNA

O In the 1950s, British scientist Rosalind Franklin

used a technique called X-ray diffraction to get

information about the structure of the DNA

molecule.

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The Work of Watson and Crick

O At the same time, James Watson, an American biologist, and Francis Crick, a British physicist, were also trying to understand the structure of DNA.

O Early in 1953, Watson was shown a copy of Franklin’s X-ray pattern.

O Watson and Crick’s breakthrough model of DNA was a double helix, in which two strands were wound around each other.

Page 11: Molecular Basis for Inheritance - WordPress.com · molecular basis of inheritance O Griffith (1927) Bacteria have the ability to transform harmless cells in to virulent ones by transferring

Summary

O Used to think that proteins not DNA were the molecular basis of inheritance

O Griffith (1927) Bacteria have the ability to transform harmless cells in to virulent ones by transferring some genetic factor from one bacteria cell to another

O Avery, MacLeod and McCarty (1944) provided direct experimental evidence that DNA, not protein, was the genetic material

O Hershey & Chase (1952) backed up that DNA was genetic material

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Summary

O Franklin (1950-1953) working in Wilkins lab, took

X-ray crystallography picture of DNA, showed

helical shape

O Died before Nobel Prize

O Watson and Crick (1953) proposed double helix

structure of DNA

O Received Nobel in 1962 with Wilkins

O Meselson & Stahl (1958) proved that DNA

replicates in a semiconservative fashion as

predicted by Crick

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DNA Timeline

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How Long is DNA?

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Complete 1-8

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The Components of DNA

O Nucleotides - building blocks (monomers) of

nucleic acid

O DNA (deoxyribonucleic acid) - nucleic acid

made up of nucleotides joined into long

strands or chains by covalent bonds

(polymer)

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Nucleic Acids and Nucleotides

O Three parts of a nucleotide :

O 5-carbon sugar called deoxyribose

O phosphate group

O nitrogenous base

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Nitrogenous Bases and Covalent Bonds

O The nucleotides in a strand of DNA are joined by

covalent bonds formed between their sugar and

phosphate groups.

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Nitrogenous Bases and Covalent Bonds

O DNA has four kinds of nitrogenous bases:

O Adenine (A)

O Guanine (G)

O Cytosine (C)

O Thymine (T)

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Nitrogenous Bases

O 2 Types of Nitrogenous Bases

O Purines

O Adenine and Guanine

O 2 Carbon rings

O Pyrimidines

O Cytosine and Thymine

O Single Carbon Ring

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Nitrogenous Bases and Covalent Bonds

O The nitrogenous bases stick

out sideways from the

nucleotide chain.

O The nucleotides can be joined

together in any order, meaning

that any sequence of bases is

possible

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Complete 9-10

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Chargaff ’s Rules

O Erwin Chargaff discovered that the percentages of

adenine [A] and thymine [T] bases are almost

equal in any sample of DNA. The same thing is

true for the other two nucleotides, guanine [G] and

cytosine [C].

O The observation that:

O [A] = [T]

O [G] = [C]

O became known as “Chargaff’s rules.”

Page 24: Molecular Basis for Inheritance - WordPress.com · molecular basis of inheritance O Griffith (1927) Bacteria have the ability to transform harmless cells in to virulent ones by transferring

Chargaff's Rule Practice#16 on POGIL

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Hydrogen Bonding

O Hydrogen bonds form

between bases, holding

the two DNA strands

together.

O Which are stronger,

covalent or hydrogen

bonds?

O Why is this important?

Page 26: Molecular Basis for Inheritance - WordPress.com · molecular basis of inheritance O Griffith (1927) Bacteria have the ability to transform harmless cells in to virulent ones by transferring

Base P

airing

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Structure of DNA

O DNA is a double helix: Two strands run in opposite directions

O One strand runs 5’ to 3’, other runs 3’ to 5’

O Carbons in Deoxyribose are numbered 1-5

O Histones: proteins that coil DNA into chromatin

O Packed and unpacked in nucleus as needed

Page 28: Molecular Basis for Inheritance - WordPress.com · molecular basis of inheritance O Griffith (1927) Bacteria have the ability to transform harmless cells in to virulent ones by transferring

Numbering Carbons

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DNA ReplicationBefore a cell divides, its DNA must

first be copied. How might the

double-helix structure of DNA

make that possible?

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Flashback…

O During S phase of the cell cycle, DNA

is replicated

O A new set of DNA must be made for

each new cell that is formed

O DNA is also passed from parent to

offspring

O Need a way to copy DNA so this can

happen

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Complete 11-15

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Semiconservative Replication

O Watson and Crick hypothesized that there must be template involved in the copying of DNAO “It has not escaped our notice that the

specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.” Watson & Crick

O Based on complementary base pairs

O If you know the sequence of one strand you can figure out the sequence of the other

O How can we do this?

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Copying the Code

O Each strand has all the information needed to reconstruct the other half by base pairing

O Strands are said to be complementary

O As each new strand forms, new bases are added following the rules of base pairing

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Template Mechanism

O Watson and Crick’s theory proven in 1950’s

O During DNA Replication:

O Two strands split

O Each strand acts as a template for the creation of a new strand

O One copy becomes two

O Each piece of DNA has one old strand and one new daughter strand

Page 35: Molecular Basis for Inheritance - WordPress.com · molecular basis of inheritance O Griffith (1927) Bacteria have the ability to transform harmless cells in to virulent ones by transferring

Summary

Page 36: Molecular Basis for Inheritance - WordPress.com · molecular basis of inheritance O Griffith (1927) Bacteria have the ability to transform harmless cells in to virulent ones by transferring

DNA Replication

O Eukaryotic chromosomes are SUPER LONG

O Replication may begin at dozens or even hundreds

of places on the DNA molecule, proceeding in both

directions until each chromosome is completely

copied

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Complete 17-20

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Role of Enzymes

O More than a dozen enzymes involved

O Nucleotides are brought in and paired

with complimentary nucleotides on

the parent strand

O Process is super fast and accurate,

only 1 error every billion nucleotides

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Replication of the Double Helix

O Replication begins at specific sites, Origins of

Replication

O Copying moves outward (in both directions)

creating bubbles

O Having multiple bubbles lets the replication

happen faster

O Each end of the bubble is a replication fork

O Eventually all the bubbles fuse

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Beginning Replication

O One of our cells can replicate its entire DNA in a

few hours

O Helicase, an enzyme unzips the DNA at the

replication fork

O Single strand binding proteins hold strands apart

like scaffolding

O Primase, an enzyme, makes an RNA primer to

guide DNA Polymerase

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DNA Polymerase

O DNA Polymerase: an enzyme which catalyzes the

antiparallel elongation of the new DNA strands

O Builds new strand 5’ to 3’ direction

O In humans 50 nucleotides per second

O DNA Polymerase does not initiate synthesis

O Only adds nucleotides to 3’ end

O Carries out mismatch repair, proofreading

O DNA nuclease removes damaged regions

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Problem with ForksO Leading strand: towards the replication fork

O One continuous string, unbroken

O Lagging Strand: away from the fork

O Series of segments: Okazaki fragments

O Joined by DNA ligase

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Excision Repair

O DNA Polymerase can “proofread” DNA to

check for errors.

O Nuclease will cut out a short piece containing

the mutation

O DNA Polymerase will then replace that piece

with new DNA nucleotides

O Ligase seals the DNA

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Telomeres

O Each time DNA replicates some nucleotides at the end of chromosomes are lost

O Lost genes?

O Nonsense sequence to protect against this

O TTAGGG repeats thousands of times

O Ends called TelomeresCreated and maintained by Telomerase

O Shorten after each replication

O Aging?

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Lets see it!

O DNA Coiling and Replication

O DNA Replication (other links on left)

O Really good!

O Chargaff’s Ratio