K. M

alo

ne

©2

00

5

Ch. 12 – DNA• Introduction to DNA (Sec. 12.1)

• History, important discoveries, who’s who in genetics

• Structure of DNA (Sec. 12.1)• Genes and the Double Helix

• Chromosomes and DNA replication (Sec. 12-2)

• Chromosome structure and function

• RNA and Protein synthesis (Sec. 12.3)• Structure and types of RNA• Transcription, Translation

• Mutations (Sec. 12.4)• Types of mutations and their significance

• Gene Regulation (Sec. 12.5)• Eukaryotes and Prokaryotes• Differentiation

K. M

alo

ne

©2

00

5

Where is DNA?

Chromatin

Nucleus

Chromatin = DNA bound to protein, arranged in units called chromosomes

DNA is located in the Nucleus of Eukaryote cells. Prokaryotes don’t have a nucleus so their DNA is floating in the cytoplasm.

Humans have 46 chromosomes

The Double HelixChromosomes are composed of two strands of DNA wrapped around each other, as shown to the left.

Sec. 12.1

Box 1

Box 1

Box 2

Box 3

K. M

alo

ne

©2

00

5

History of DNA• Fredrick Griffith (1928) wanted to find

out how bacteria caused pneumonia, his experiment:Disease-causing bacteria (smooth colonies)

Harmless bacteria (rough

colonies)Heat-killed,

disease-causing bacteria (smooth colonies)

Control(no growth)

Heat-killed, disease-causing bacteria (smooth colonies)

Harmless bacteria (rough colonies)

Dies of pneumonia

Lives

Live, disease-causing

bacteria (smooth colonies)

Dies of pneumonia

Fred killed Kenny!

Griffith found that bacteria can “transform” each other, or share information, like how to kill a mouse

Lives

I didn’t die?

But how? What did they pass

to each other?

Box 4

K. M

alo

ne

©2

00

5

History of DNA• Oswald Avery (1944) repeated Griffith’s work

and discovered that nucleic acid DNA stores and transmits the genetic information from one generation of an organism to the next

He’s such a dork.

Alfred and Martha

Hmm..she’s cute!

•Alfred Hershey and Martha Chase and the Hershey-Chase Experiment (1952):

-Studied viruses that infect bacteria = bacteriophage-Bacteriophages = “bacteria eaters” inject their own DNA into cell and use the cell to produce many copies of themselves, killing the bacteria because it splits open, releasing hundreds of new viruses! Eeek! -What Hershey and Chase found:

-Used “markers” or radioactive isotopes-Discovered that the genetic material of bacteriophage was DNA, not protein

Box 5

Box 6

Box 7

K. M

alo

ne

©2

00

5

What is DNA? DeoxyriboNucleic Acid• DNA is a molecule made up of Nucleotides

• Nucleotides are made up of 3 things:1. 5- carbon sugar called Deoxyribose

2. A nitrogenous base (contains nitrogen)3. A phosphate group (P= phosphate)

PP

sugar

aden

ine

guanin

e

sugarsugar

PP

cyto

sine

thym

ine

Purines have 2 rings Pyrimidines have 1 ring

These bases, A G C T, are arranged into a sequence, or a gene, like letters of our alphabet are arranged into words.

Pyrimidines have a “y” in their name

No “y”!!

sugar

Nitr

ogen

ous

base

Nitr

ogen

ous

base

P= phosphate

sugar

Label the figure!

1. Purines= 2 kinds

A = Adenine (AD-uh-neen) G = Guanine (GWAH-neen)

2. Pyrimidines = 2 kindsC = Cytosine (SY-tuh-zeen)

T = Thymine (THY-meen)

sugar

P P

•There are 2 types of Nitrogenous bases in DNA

Box 8

Box 9

Box 8

Box 10

Box 11

K. M

alo

ne

©2

00

5

Look at it this way…Deoxyribonucleic Acid

Sugar Deoxyribose

PhosphateNucleotide

Tree Map!!!!!

Purines 2

rings

Pyrimidines 1 ring

Adenine Guanine Thymine Cytosine

Pyrimidines, Thymine and Cytosine, all have “y’s” in their names!!!

Purines, Adenine and Guanine, are too “pure” to be tainted with mere a “y”

Copy the tree map onto the

paper provided and staple to

your class notes.

K. M

alo

ne

©2

00

5

• Erwin Chargoff reported that in any DNA sample:– % of cytosine (C) bases are almost = to % of

guanine (G)– % of adenine (A) are almost = % of thymine (T)

– This is known as Chargoff’s Rules

Chargoff’s Rules

Now, we get to the most famous of all geneticists………and the most controversial

discoveries….drum roll please…..

%Adenine = %Thymine

%Guanine = %Cytosine

Box 12

K. M

alo

ne

©2

00

5

Rosalind Franklin• Rosalind Franklin (1950’s) studied DNA

structure by using X-ray diffraction• Discovered that the bases, A G C and T,

were near the center of the X, or the double helix

Story #1:Maurice Wilkens, Franklin’s colleague, showed her photos to James Watson, without her knowledge or consent. For Watson, seeing Franklin’s work was like fitting the missing piece in the puzzle of DNA’s structure. "My jaw fell open and my pulse began to race," Watson said. He went back to his lab and along with Francis Crick, assembled the double helix structure of DNA.

THE CONTROVERSY

Rosalind died of ovarian cancer in 1958.

Story #2:Rosalind was in love with Watson, and she showed him her work because of her love and trust. Once Watson saw her photos, he used the data to piece together the information he needed to assemble the structure of DNA. He and Crick became famous, while hardly knows about Rosalind.

What is the REAL story?

“Photo 51”

Box 13

K. M

alo

ne

©2

00

5

Watson and Crick

• Francis Crick and James Watson (~1953)

Watson and Crick identified and linked together key pieces of research, and along with their own discoveries, described the basic structure of DNA

Box 14

In 1962, the Nobel Prize was awarded to Watson, Crick, and Wilkins (Rosalind Franklin’s colleague). What did Wilkins do to deserve such a prize?

The “twisted ladder” shape of DNA became known as the double helix. The 2 DNA strands wind around each other, like a winding staircase

Box 15

James Watson

Francis Crick

Hee hee, my dear Watson we’ve discovered the secret to life! Yes, you bloody

fool, we discovered the double helix!

K. M

alo

ne

©2

00

5

Double Helix Structure

Key

Adenine (A)

Thymine (T)

Cytosine (C)

Guanine (G)

Each strand is made up of a chain of nucleotides.

Box 16

Nucleotide

Box 17

Ribose and Phosphates join together forming the backbone of the DNA molecule

Box 18

The 2 strands are held together by hydrogen bonds between the bases Adenine and Thymine and between Guanine and Cytosine.

Box 20

Hydrogen

bonds

Box 21

Sugar-phosphate backbone

Box 19

DNA is a double helix in which two strands are wound around each other (like a twisted

ladder).

Box 22

K. M

alo

ne

©2

00

5

Hydrogen Bonds• Hydrogen bonds (sharing of one electron

between 2 Hydrogens) between the nucleotides (AGCT) holds the 2 strands of DNA together with a fairly strong force

H H

DNA strand: A G C T G G C T A A T C GComplementa

ry DNA Strand:

T C C C C T TG G GA A A

A + T

=

love

G + C =

Love Forever!

A=T G=C

Sugar-phosphate backbone

Nucleotide

Hydrogen

bonds

The binding together of the nucleotides with Hydrogen bonds is called Base Pairing

Box 23

K. M

alo

ne

©2

00

5

Horses = 64 chromosome

s

Cows = 60 chromosome

s

Cats and Dogs = 38

chromosomes

Chickens = 78

chromosomes

Who has DNA? All living things do!• Prokaryotes (bacteria) don’t have a nucleus,

and their DNA is found floating in the cytoplasm; usually they have a single strand of DNA, or chromosome

• Of course, Eukaryotes are more complicated!– Eukaryote = YOU! And, any organism with

their DNA inside the nucleus. Eukaryotes generally have 1000X more DNA than bacteria

– Eukaryote DNA is organized into Chromosomes

Having MORE chromosomes doesn’t mean an organism is bigger or smarter!Cows are smarter than humans?NO!Chickens are bigger and smarter than dogs? Hmm…..

Humans = 46 chromosomes

Box 24

Fly = 8 chromosome

s

Box 24

K. M

alo

ne

©2

00

5

DNA double helix

How DNA fits into a cell1. Eukaryotic chromosomes contain DNA wrapped around proteins called histones.

Box 25 2. DNA and

histone together = chromatin

Box 27

3. Wound strands of chromatin are called nucleosomes, and these are tightly coiled and supercoiled to form chromosomes

Box 29Histones Box

26

Chromatin Box 28

Coils

Box 31

Super Coils

Box 32

ChromosomeBox 33 Nucleosomes

Box 30

K. M

alo

ne

©2

00

5

DNA Replication• Watson and Crick realized that by the rules of

Base Pairing, each strand of DNA has the information needed to reconstruct the opposite strand.

• Because each strand can reconstruct its opposite strand, the strands are said to be Complementary

DNA strand: A G C T C C G T C A A T T G

Opposite strand:T T TC C CG G G GA A A A

Complementary DNA strands

You look very nice

today!

Why, thank you! You look rather lovely yourself.

Complementary Strand of DNA

Complementary Strand of DNA

Box 34

Replication = the process where DNA makes a copy of itself, base by base, producing 2 new complementary strands , and each strand serves as a template for the new strand.

Box 35

K. M

alo

ne

©2

00

5

Original strand = blue

DNA Replication

New strand = orange

Growth

Growth

During Replication, the new strand is made from the original strand, which serves as a template.

The new strand (orange) is “complementary” to the new strand (blue).

New strand = orange

Box 37

Original strand = blue

Box 38

Replication Fork Box

40

Replication ForkBox 41

Nucleotides

Box 36

DNA polymerase

Box 39

DNA polymerase = an enzyme that joins two nucleotide bases to produce a DNA molecule and “proofreads” each copy to make sure it’s correct

K. M

alo

ne

©2

00

5

New strand = orangeOriginal strand = blue

Replication Fork

New strand = orange

Original strand = blue

Replication Fork

Growth

Growth

What does DNA have to do 1st, before it can replicate?

What’s happening here?

DNA Polymerase

Nucleotides

Answer: It has to unwind! Open up!! Unzip!!!!Box 42

K. M

alo

ne

©2

00

5

How does it…..?• Problem:

– DNA is in the nucleus and never leaves– Proteins are made in the cytoplasm– How does the instructions for the

protein, the DNA, get out to the ribosomes?

• Solution:– DNA doesn’t leave the nucleus, but the

information from DNA does– Send a copy of the instructions!

Section 12-3

Introducing the messenger service……. RNA

RNA = Ribonucleic AcidBox 43

K. M

alo

ne

©2

00

5

DNA to RNA, the 1st step• Have you ever heard someone say, “I can’t help

it, it’s in my genes!” or “It’s genetic.”• They’re talking about something inherited from

their parents- not their actual “jeans” of course.

•Genes = coded DNA instructions that control the production of proteins within the cell

•The double helix DNA structure doesn’t explain how a gene works, so to understand that, we have to decode the information within a gene

Box 44

1st step in decoding genes = copy part of the nucleotide sequence from DNA to RNA

Box 45 RNA (ribonucleic acid)

= contains coded information for making proteins

Box 46

K. M

alo

ne

©2

00

5

RNA Structure• RNA is like DNA, but with 3 main differences:

– 1. Sugar in RNA is ribose instead of deoxyribose– 2. RNA is generally single-stranded, not double

stranded– 3. RNA contains Uracil instead of Thymine

Think of RNA this way: Would you give your friend your original CD, or would you give

them a copy of it?

You’d give them a copy, of course! If you keep the original safe, then you can make thousands of copies of it as needed, as often as you want. DNA and RNA replication functions in the same way.

RNA

(YER-a-sil)

DNABox 48

and 49

Box 47

K. M

alo

ne

©2

00

5

Types of RNA

• 3 main types of RNA:1. Messenger RNA (mRNA)2. Ribosomal RNA (rRNA)3. Transfer RNA (tRNA)

Box 50

Each type of RNA may have a different function, but all RNA has a single goal – to make proteins

It’s all they care about, all they want to do, they are obsessed with making proteins!

Box 51

K. M

alo

ne

©2

00

5

Different Functions of RNA

•rRNA (ribosomal RNA) = what makes up a ribosome (the organelles that make proteins) thus it’s called “ribosomal” RNA

Box 53

•tRNA (transfer RNA) = a molecule that “transfers” amino acids to the ribosome as directed by the coded mRNA, to form proteins

Box 54

Box 52•mRNA (messenger RNA) = a

messenger service, they carry messages (copies of a gene) from DNA, in the form of RNA, to the rest of the cell

K. M

alo

ne

©2

00

5

Transcription

Adenine (DNA and RNA)Cystosine (DNA and RNA)Guanine(DNA and RNA)Thymine (DNA only)Uracil (RNA only)

1. RNA polymerase binds to DNA and separates the 2 DNA strands (unzips them)

2. RNA polymerase only binds to regions of DNA called “promotors” that have specific base sequences that say, “Hey, start here!”

3. RNA polymerase then uses 1 strand of DNA as a “template” to assemble the strand of RNA

RNA polymerase

Box 55

•Transcription = production of RNA molecules by copying part of the DNA nucleotide sequence into a complementary sequence of RNA

–Requires an enzyme called RNA polymerase

Transcription Process (How it happens):

Box 56

K. M

alo

ne

©2

00

5

RNA Editing• Would you turn in the 1st draft of your

English paper? – No! (I hope not!)

• In the same way, RNA must be ‘edited’ before its ready to go into action

• Eukaryote DNA contains regions that are not used in making proteins called….– Introns = nucleotide sequences not involved

in protein synthesis, they are cut out of RNA

– Exons = DNA sequences that code for proteins

removed removed

Exon Exon Exon

Exon Intron Exon Intron ExonRNA

“edited” mRNA

Box 57

Box 58

RNA editing is cutting out the introns, and splicing the exons together

Box 59

K. M

alo

ne

©2

00

5

20 amino acids and only 4 nucleotide bases to code for them, AGCT, sounds impossible, but it’s not.

The Genetic Code• Proteins – made by joining amino acids into

long chains called polypeptides• Any combination of the 20 different amino

acids make up a protein• The arrangement of amino acids determines

what a protein is and what it does• So, we have the instructions (DNA) for

making a protein, but how do we translate that into a protein?

• We use the Genetic Code!

Poly = many!

Peptide = protein

Box 60

Box 61

Box 62

The Genetic Code = the language of mRNA instructions for making proteins

Box 63

K. M

alo

ne

©2

00

5

How it works…• The genetic code is read 3 letters, or bases,

at a time, and this forms a sort of “word”

• Each 3 letter “word” is in mRNA is known as a codon

• Codon = 3 consecutive (in a row) nucleotide bases that specify 1 amino acid to be added to the polypeptide chainmRNA sequence = UCGCACGGU

Now, read it 3 bases at a

time…

UCG CAC GGU

Each codon represents a different amino acid!

GlycineSerine –Histidine –

Box 64

K. M

alo

ne

©2

00

5

How It’s Done4 different bases (AGCT) = 64 possible 3-base codons

4 x 4 x 4 = 64

stop

stop1

23

Some amino acids, like Valine, Serine, Alanine, Arginine, etc. can be specified by more than one codon.

Box 65

Some codons, like AUG, specify only 1 amino acid. Ex. AUG can either be a “start” codon, or a Methionine.

Box 65

There are 3 “stop” codons that don’t code for any amino acid. Stop codons act like the period at the end of a sentence- they signal the end of the polypeptide sequence.

Box 65

K. M

alo

ne

©2

00

5

Can You Break the Code?

DNA: AAC GTA TGC GAT

mRNA: UUG CAU ACG CUA

Amino Acid Sequence:

Leu His Thr Leu

1

2

3

K. M

alo

ne

©2

00

5

Translation• You have the instructions (sequence of

nucleotide bases), but who “reads” them?

• The Ribosome “reads” the sequences in a process called Translation

You, go there, and you, go here, and stop pushing each other! Get in line,

you AA idiots!

Box 66

Translation = occurs in the ribosomes, and is when the cell uses information from mRNA to produce, or assemble, proteins

K. M

alo

ne

©2

00

5

Translation

nucleus

mRNALysine

tRNAMethionine

Phenylalanine

mRNA Start codon

ribosome

cytoplasm

1. Messenger RNA is transcribed in the Nucleus then it enters the cytoplasm and attaches to a ribosome.

Box 67

2. As each codon of the mRNA moves through the ribosome, the proper amino acid is brought to the ribosome by tRNA (transfer RNA).

Box 67

3. Each tRNA carries only 1 amino acid, and has 3 unpaired bases on the end, where it attaches to the mRNA.Because these bases are the opposite of the mRNA, they are called the Anticodon.

Box 67

K. M

alo

ne

©2

00

5

ribosome

ribosome

tRNA

tRNA

mRNA

mRNA

Growing polypeptide chain

Lysine

Peptide Bond

4. The ribosome forms a Peptide bond between the 1st and 2nd amino acids, and releases the tRNA. It then moves on to the next codon, where another tRNA brings it the amino acid that codon specifies.

Box 67

5. The polypeptide chain continues to grow until the ribosome reaches a “stop” codon on the mRNA. It then releases the newly formed polypeptide chain and the mRNA, completing translation.

Box 67

K. M

alo

ne

©2

00

5

Roles of RNA and DNA• DNA is the “Master Plan” for a building

(your body), and builders never take the master plan to a job site- it’s too important.

• Instead, they make inexpensive copies called Blueprints

• DNA is safely stored in the nucleus, and the copies of DNA, or the RNA, go out into the cytoplasm where the proteins are built.

• What else can we compare this process to?

A painting by Renoir- the original is safe in a museum, but anyone can buy a print of it.A designer dress- copies are made and sold, but the original is kept with the designer.

Your favorite CD- you make copies of it and keep the original safe at home.

Box 68

K. M

alo

ne

©2

00

5

•Genes code for enzymes and proteins that do everything from controlling the color of a flower petal to ones that determine your blood type.

Genes and Proteins• Most Genes contain instructions for assembling

proteins.•Many proteins are enzymes, and all enzymes are proteins that catalyze and regulate chemical reactions

•Proteins are the tools specifically designed to build or operate a part of a living cell.

Box 69

Box 70

Genes contain instructions for proteins and enzymes, the molecules that make

all life possible.

An important genetics concept!

Box 71

K. M

alo

ne

©2

00

5

Mutations• Everyone makes mistakes, it’s a part of life.• Genetic mistakes are called Mutations• Mutation = any change in the genetic

material• All mistakes aren’t bad, and all Mutations

ain’t all bad either! • Types of mutations:

1. Point mutations = changes in 1 point, or

1 nucleotideThese can be either:Substitutions = 1 base is substituted for

anotherInsertions = 1 base is inserted into the DNA

sequenceDeletions = 1 base is deleted from the DNA

sequence

Section 12-4

The key to remember is a Point Mutation occurs at 1 point in the DNA sequence

Box 72

Box 73

K. M

alo

ne

©2

00

5

Point Mutations• Changes at a single point, or a single

base, can either have NO effect (not change the amino acid specified), or have a HUGE effect

• Substitutions do NOT have as big of an effect as….– Insertions and Deletions usually have a

BIG effect on the amino acid sequence

• Try adding another letter to the word “CAT”

If you add an extra letter to CAT, it either becomes nonsense, or it has a different meaning!

CAT CYATCATS

Substitutions do NOT cause Frameshift mutations!!!

Insertions and Deletions DO cause Frameshift mutations!!!

Box 74

Changes like this are called Frameshift Mutations because they are mutations that shift the “reading frame” by one letter

Box 75

K. M

alo

ne

©2

00

5

Amino: Met Arg Thr Leu Acids

Frameshifts

DNA: TAC GCA TGG AAT

mRNA: AUG CGU ACC UUA

Amino: Met Arg Thr Leu Acids

Substitution

DNA: TAC GTA TGG AAT

mRNA: AUG CAU ACC UUA

DNA: TAC GCA TGG AAT

mRNA: AUG CGU ACC UUA

Amino: Met Arg Thr Leu Acids

Insertion

DNA: TAT CGC ATG GAA T

mRNA: AUA GCG UAC CUU A

Amino: Ile Ala Try Leu Acids

Big change, mRNA codes for different

amino acids!

No change, mRNA still codes for the amino acid Arg

K. M

alo

ne

©2

00

5

What about deletions?

THE FAT DOG ATE THE PIE

Deletion

THE FAT DOG ATE THE PIE

TEF ATD OGA TET HEP IE

Utter nonsense. The reading frame shift made the sentence change just as a deletion or insertion would change the amino acid sequence of a protein

If you delete the “H” in the, it moves the whole “reading” frame over one letter!

K. M

alo

ne

©2

00

5

Types of Mutations • 2. Chromosomal Mutations = involve

much larger changes because: – They involve the # or structure of

chromosomes themselves– And chromosomes contain 1000’s of

genes!!!!• What would happen if you lost a whole

chromosome? Added a whole chromosome?

You’d either be dead, or you’d have a bad disease!

Box 76

K. M

alo

ne

©2

00

5

Chromosomal Mutations

Deletion

Duplication

Inversion

Translocation

4 Types of Chromosomal Mutations:1. Deletions = lose part of a chromosome (many genes!)

Box 77

2. Duplications = gain extra parts of a chromosome, or an extra whole chromosome3. Inversions = reverse the direction of parts of a chromosome- mixes it up!4. Translocations = part of a chromosome breaks off and attaches to another chromosome

K. M

alo

ne

©2

00

5

Effects of Mutations• Many mutations are neutral, meaning they have little

effect on the expression of genes or the function of proteins coded by the genes

Box 78

Box 78

•Harmful mutations are the cause of many human genetic disorders, like cancer

Box 78

•Mutations that result in a BIG change in the DNA or amino acid sequences are usually harmful- they produce defective proteins or no protein at all!

Box 79

•Beneficial mutations (yes there are some!) can give an organism a survival advantage (evolution

K. M

alo

ne

©2

00

5

Gene Regulation• Not all genes are expressed all the time• Expressed genes = a gene that is transcribed

into mRNA, which leads to creating a protein• Humans have ~30-40,000 genes and our

bodies can’t be making all those proteins all at once!

• In the jumble of DNA, there are patterns, and biologists have identified patterns that represent how gene expression is controlled

Section 12-5

Box 80

–3 Examples are:–Promotors = binding sites for RNA polymerase–Start and Stop signals = starts and stops transcription–Operons = group of genes that operate together

Box 81

K. M

alo

ne

©2

00

5

Eukaryote Gene Regulation• Prokaryote = organisms without a nucleus,

most are bacteria• Eukaryotes = (YOU!) organisms with their

DNA contained in a nucleus (humans, plants, animals, fungi, etc.)

• Eukaryote genes are mostly controlled individually and have complex regulatory sequences

1. TATAA = the “TATA” box, a sequence that occurs before the start codon, a place where RNA polymerase binds2. Promotors = sequences that are signals for RNA polymerase found just before the TATA box

Box 82

K. M

alo

ne

©2

00

5

Typical Gene Structure

Promoter(RNA polymerase binding site)

Regulatory sites DNA

strand

Start transcription

Stop transcription

Direction of Transcription

K. M

alo

ne

©2

00

5

Development and Differentiation• Differentiation = when cells become specialized

in structure and functionEarly development, in the beginning, all of an embryo’s cells have the ability to become anything- heart, eye, leg, toe, wing, etc. Later development, cells specialize and become the toe, heart, leg or wing cell, and once they have specialized, they lose the ability to be anything else

Normal fruit fly Legs instead of antennae!Caused by Human Hox-13 mutation

Box 83

Hox genes = series of genes that control the differentiation of cells and tissues in the embryo, the BODY PLAN. A mutation in the Hox Genes can completely change the organs that develop in specific parts of the body.

Box 84