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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

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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

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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?

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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 aint bout that life doe.

Alfred and Martha

Aye, what yo name

is?

•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

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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 These bases, A G

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

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

•There are 2 types of Nitrogenous bases in DNA

Adenine goes with Guanine A-G

Cytosine goes with Thymine C-TThymine (DNA only)Uracil (RNA only)

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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

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

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!

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Double Helix Structure

Key

Adenine (A)

Thymine (T)

Cytosine(C)

Guanine (G)

Each strand is made up of a chain of nucleotides. Nucleotide

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

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

Hydrogen

bonds

Sugar-phosphate backbone

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

ladder).

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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 TA 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

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Horses = 64 chromosome

s

Cows = 60

Cats and Dogs = 38

Chickens = 78

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

Fly = 8

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DNA double helix

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

2. DNA and histone together = chromatin

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

Histones

Chromosome

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DNA Replication

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

Complementary Strand of DNA

Complementary Strand of DNA

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.

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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).

Replication Fork

Nucleotides

DNA polymerase

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

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

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

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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 Acid

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DNA to RNA, the 1st step• “I can’t help it, it’s in my genes!” or

“It’s genetic.”

•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

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

RNA (ribonucleic acid) = contains coded information for making proteins

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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?

(YER-a-sil)

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Types of RNA

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

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!

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Different Functions of RNA

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

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

•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

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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

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

–Requires an enzyme called RNA polymeraseTranscription Process (How it

happens):

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RNA Editing

removedremoved

Exon Exon Exon

Exon Intron Exon Intron ExonRNA

“edited” mRNA

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

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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

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

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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

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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

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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

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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!

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

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Translation

nucleus

mRNALysine

tRNA

Methionine

Phenylalanine

mRNA Start codon

ribosome

cytoplasm

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ribosome

ribosome

tRNA

tRNA

mRNA

mRNA

Growing polypeptide chain

Lysine

Peptide Bond

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

building (your body).• RNA=“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?

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•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.

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

all life possible.

An important genetics concept!

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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 73

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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!!!

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

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Amino: Met Arg Thr Leu Acids

Frameshifts

DNA: TAC GCA TGG AATmRNA: 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

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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!

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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

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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

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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

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

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

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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

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

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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

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Typical Gene Structure

Promoter(RNA polymerase binding site)

Regulatory sites DNA

strand

Start transcription

Stop transcription

Direction of Transcription

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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

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.