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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’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
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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
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
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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.
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• 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
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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”
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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
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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
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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.
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Nucleotide
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Ribose and Phosphates join together forming the backbone of the DNA molecule
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The 2 strands are held together by hydrogen bonds between the bases Adenine and Thymine and between Guanine and Cytosine.
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Hydrogen
bonds
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Sugar-phosphate backbone
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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 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
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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
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Fly = 8 chromosome
s
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DNA double helix
How DNA fits into a cell1. Eukaryotic chromosomes contain DNA wrapped around proteins called histones.
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histone together = chromatin
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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
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Super Coils
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ChromosomeBox 33 Nucleosomes
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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
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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).
New strand = orange
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Original strand = blue
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Replication Fork Box
40
Replication ForkBox 41
Nucleotides
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DNA polymerase
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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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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
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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 AcidBox 43
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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
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1st step in decoding genes = copy part of the nucleotide sequence from DNA to RNA
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= 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?
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
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Types of RNA
• 3 main types of RNA:1. Messenger RNA (mRNA)2. Ribosomal RNA (rRNA)3. Transfer RNA (tRNA)
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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
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•tRNA (transfer RNA) = a molecule that “transfers” amino acids to the ribosome as directed by the coded mRNA, to form proteins
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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
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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
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•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):
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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
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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
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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 –
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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.
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Some codons, like AUG, specify only 1 amino acid. Ex. AUG can either be a “start” codon, or a Methionine.
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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.
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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!
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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
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.
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2. As each codon of the mRNA moves through the ribosome, the proper amino acid is brought to the ribosome by tRNA (transfer RNA).
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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.
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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.
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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.
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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.
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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.
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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
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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!!!
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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 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
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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!
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Chromosomal Mutations
Deletion
Duplication
Inversion
Translocation
4 Types of Chromosomal Mutations:1. Deletions = lose part of a chromosome (many genes!)
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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
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•Harmful mutations are the cause of many human genetic disorders, like cancer
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•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!
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•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
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–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
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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.
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