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hapter 12: From DNA to Protein: Genotype to Phenotype CHAPTER 12 From DNA to Protein: Genotype to Phenotype

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Page 1: Chapter 12: From DNA to Protein: Genotype to Phenotype CHAPTER 12 From DNA to Protein: Genotype to Phenotype

Chapter 12: From DNA to Protein: Genotype to Phenotype

CHAPTER 12From DNA to Protein:

Genotype to Phenotype

Page 2: Chapter 12: From DNA to Protein: Genotype to Phenotype CHAPTER 12 From DNA to Protein: Genotype to Phenotype

Chapter 12: From DNA to Protein: Genotype to Phenotype

Genotype to Phenotype

Genes are made up of DNA (genotype).

Genes cannot directly produce a phenotype.

Genes must be expressed (phenotype) as polypeptides.

Page 3: Chapter 12: From DNA to Protein: Genotype to Phenotype CHAPTER 12 From DNA to Protein: Genotype to Phenotype

Chapter 12: From DNA to Protein: Genotype to Phenotype

DNA, RNA, and the Flow of Information

RNA differs from DNA in three ways: It is single-stranded, Its sugar molecule is ribose rather

than deoxyribose, and Its fourth base is uracil rather than

thymine. Adenine pairs with uracil

Page 4: Chapter 12: From DNA to Protein: Genotype to Phenotype CHAPTER 12 From DNA to Protein: Genotype to Phenotype

Chapter 12: From DNA to Protein: Genotype to Phenotype

DNA, RNA, and the Flow of Information

The central dogma of molecular biology is DNA RNA protein.

Review Figure 12.2

Page 5: Chapter 12: From DNA to Protein: Genotype to Phenotype CHAPTER 12 From DNA to Protein: Genotype to Phenotype

Chapter 12: From DNA to Protein: Genotype to Phenotype

DNA, RNA, and the Flow of Information - Summary

A gene is transcribed to produce messenger RNA (mRNA).

mRNA is complementary to one of the DNA strands

Transfer RNA ((tRNA) translates sequence of bases in mRNA into appropriate sequence of amino acids.

Amino acids join together (peptide bonds) to form proteins.

Review Figure 12.3

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Chapter 12: From DNA to Protein: Genotype to Phenotype

Figure 12.3

Figure 12.3

figure 12-03.jpg

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Chapter 12: From DNA to Protein: Genotype to Phenotype

Transcription – synthesis of RNA from DNA

Transciption requires the enzyme RNA polymerase, RNA nucleotides, and a DNA template.

Transcription occurs in the nucleus.

The product, a RNA transcript, is sent to the cytoplasm where translation occurs.

Page 8: Chapter 12: From DNA to Protein: Genotype to Phenotype CHAPTER 12 From DNA to Protein: Genotype to Phenotype

Chapter 12: From DNA to Protein: Genotype to Phenotype

Transcription

Transcription is divided into three processes:

Initiation, Elongation, and termination

Page 9: Chapter 12: From DNA to Protein: Genotype to Phenotype CHAPTER 12 From DNA to Protein: Genotype to Phenotype

Chapter 12: From DNA to Protein: Genotype to Phenotype

Initiation

Transcription begins at a promoter – a special sequence of DNA .

The promoter determines the direction, which strand to read, and direction to take

RNA polymerase binds to the promoter. Once the polymerase is attached to the

promoter DNA, the DNA strands unwind and transcription begins.

Page 10: Chapter 12: From DNA to Protein: Genotype to Phenotype CHAPTER 12 From DNA to Protein: Genotype to Phenotype

Chapter 12: From DNA to Protein: Genotype to Phenotype

Elongation

As RNA polymerase moves along the DNA, it continues to unwind DNA about 20 bases pairs at a time.

One side of the unwound DNA acts as template for RNA synthesis

RNA transcript is formed by complementary base pairings.

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Chapter 12: From DNA to Protein: Genotype to Phenotype

Termination

Specific DNA base sequences terminate transcription.

Pre-mRNA is released. Review Figure 12.4 The resulting RNA transcript may

be mRNA, tRNA, or rRNA.

Page 12: Chapter 12: From DNA to Protein: Genotype to Phenotype CHAPTER 12 From DNA to Protein: Genotype to Phenotype

Chapter 12: From DNA to Protein: Genotype to Phenotype

Messenger RNA (mRNA) carries a genetic message from DNA to the protein synthesizing machinery of the cell (ribosomes)

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Chapter 12: From DNA to Protein: Genotype to Phenotype

Figure 12.4 – Part 1

Figure 12.4 – Part 1

figure 12-04a.jpg

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Chapter 12: From DNA to Protein: Genotype to Phenotype

Figure 12.4 – Part

2Figure 12.4 – Part 2

figure 12-04b.jpg

Page 15: Chapter 12: From DNA to Protein: Genotype to Phenotype CHAPTER 12 From DNA to Protein: Genotype to Phenotype

Chapter 12: From DNA to Protein: Genotype to Phenotype

The Genetic Code

The genetic code consists of triplets of nucleotides (codons).

Since there are four bases, there are 64 possible codons (43)

There are more codons than different amino acids.

Page 16: Chapter 12: From DNA to Protein: Genotype to Phenotype CHAPTER 12 From DNA to Protein: Genotype to Phenotype

Chapter 12: From DNA to Protein: Genotype to Phenotype

The Genetic Code

AUG codes for methionine and is the start codon.

UAA, UAG, and UGA are stop codons.

Stop codons indicate the end of translation.

The other 60 codons code only for particular amino acids.

Page 17: Chapter 12: From DNA to Protein: Genotype to Phenotype CHAPTER 12 From DNA to Protein: Genotype to Phenotype

Chapter 12: From DNA to Protein: Genotype to Phenotype

The Genetic Code

Since there are only 20 different amino acids, the genetic code is redundant; that is, there is more than one codon for certain amino acids.

However, a single codon does not specify more than one amino acid.

Review Figure 12.5

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Chapter 12: From DNA to Protein: Genotype to Phenotype

The Universal Genetic Code

The genetic code appears to be nearly universal.

Provides a common language for evolution.

Implications for genetic engineering.

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Chapter 12: From DNA to Protein: Genotype to Phenotype

Figure 12.5

Figure 12.5

figure 12-05.jpg

Page 20: Chapter 12: From DNA to Protein: Genotype to Phenotype CHAPTER 12 From DNA to Protein: Genotype to Phenotype

Chapter 12: From DNA to Protein: Genotype to PhenotypePreparation for Translation: Linking RNA’s,

Amino Acids, and Ribosomes

Translation occurs at the ribosomes.

Translate the message from sequence of nucleotides to sequence of amino acids

Page 21: Chapter 12: From DNA to Protein: Genotype to Phenotype CHAPTER 12 From DNA to Protein: Genotype to Phenotype

Chapter 12: From DNA to Protein: Genotype to Phenotype

Components of Translation

Ribosomes – small and large subunits

mRNA (messenger RNA) tRNA (transfer RNA) tRNA transfer an amino acid. tRNA has a sequence of 3 bases

known as the anticodon that is complementary to mRNA codon

amino acids are linked in codon-specified order per mRNA.

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Chapter 12: From DNA to Protein: Genotype to Phenotype

Figure 12.7

Figure 12.7

figure 12-07.jpg

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Chapter 12: From DNA to Protein: Genotype to Phenotype

Example of Process

The DNA coding region for proline is

GGG which is transcribed to The mRNA codon CCC which

binds to The tRNA with the anticodon GGG

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Chapter 12: From DNA to Protein: Genotype to Phenotype

Activating Enzymes link tRNA and amino acids

A family of activating enzymes – aminoacyl-tRNA synthetases_ attach specific amino acids to their appropriate tRNA’s to from charged tRNA

The amino acid is attached to the 3’ end of tRNA with a high energy bond

Review Figure 12.8

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Chapter 12: From DNA to Protein: Genotype to Phenotype

Ribosomes

The ribosome consist of a large and a small subunit.

When not active in translation, the ribosomes exist as separate units.

They can come together and separate as needed.

Review Figure 12.9

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Chapter 12: From DNA to Protein: Genotype to Phenotype

Figure 12.9

Figure 12.9

figure 12-09.jpg

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Chapter 12: From DNA to Protein: Genotype to Phenotype

Three Phases of Translation

Initiation Elongation Termination

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Chapter 12: From DNA to Protein: Genotype to Phenotype

Translation: Initiation

A sequence of mRNA (initiation factors) binds to the small subunit of a ribosome.

Aminoacyl tRNA bearing UAC binds to the start codon.

Large subunit of ribosome joins the complex Review Figure 12.10

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Chapter 12: From DNA to Protein: Genotype to Phenotype

Figure 12.10Figure 12.10

figure 12-10.jpg

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Chapter 12: From DNA to Protein: Genotype to Phenotype

Elongation – A Four Step Process

A charged tRN moves into the ribosome and occupies the A site. Its anticodon matches the mRNA codon

The polypeptide chain is transferred. Ribosome moves along the mRNA.

Empty tRNA is ejected via the E site. tRNA with peptide chains moves to P

site. A is empty. Repeat

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Chapter 12: From DNA to Protein: Genotype to Phenotype

Figure 12.11 – Part 1

Figure 12.11 – Part 1

figure 12-11a.jpg

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Chapter 12: From DNA to Protein: Genotype to Phenotype

Figure 12.11 – Part 2

Figure 12.11 – Part 2

figure 12-11b.jpg

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Chapter 12: From DNA to Protein: Genotype to Phenotype

Translation: Termination

The presence of a stop codon (UAA, UAG, or UGA) in the A site of the ribosome causes translation to terminate.

Both tRNA and the polypeptide are released from the P site.

The ribosomes separate Review Figure 12.12

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Chapter 12: From DNA to Protein: Genotype to Phenotype

Figure 12.12

Figure 12.12

figure 12-12.jpg

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Chapter 12: From DNA to Protein: Genotype to Phenotype

4 Sites for tRNA Binding

T (transfer) site is where tRNA + amino acids first attaches to the ribosome.

The A (amino acid) site is there the tRNA anticodon binds to mRNA codon

The P (polypetide) site is where the amino acids are bonded together.

The E (exit) site is where the tRNA will leave the ribosome to pick up additional amino acids.

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Chapter 12: From DNA to Protein: Genotype to Phenotype

Regulation of Translation

Antibiotics can interfere with translation

Erythromycin plugs the exit channel so the polypeptide chain cannot leave the ribosome.

Review Table 12.2

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Chapter 12: From DNA to Protein: Genotype to Phenotype

Regulation of Translation

In a polysome, more than one ribosome moves along the mRNA at one time.

Multiple copies of the same protein is made for a single mRNA.

Review Figure 12.13

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Chapter 12: From DNA to Protein: Genotype to Phenotype

Figure 12.13

Figure 12.13

figure 12-13.jpg

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Chapter 12: From DNA to Protein: Genotype to Phenotype

Posttranslational Events

The functional protein may vary from the polypeptide chain that is originally released.

Signals contained in the amino acid sequences of proteins direct them to cellular destinations.

And polypeptides may be altered by the addition of chemical groups that affect function of the protein.

Review Figure 12.14

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Chapter 12: From DNA to Protein: Genotype to Phenotype

Figure 12.14

Figure 12.14

figure 12-14.jpg

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Chapter 12: From DNA to Protein: Genotype to Phenotype

Posttranslational Events

Protein synthesis begins on free ribosomes in the cytoplasm.

Those proteins destined for the nucleus, mitochondria, and plastids are completed in the cytoplasm and have signals that allow them to bind to and enter destined organelles.

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Chapter 12: From DNA to Protein: Genotype to Phenotype

Posttranslational Events

Proteins destined for the ER, Golgi apparatus, lysosomes, and outside the cell complete their synthesis on the ER surface.

They enter the ER by the interaction of a hydrophobic signal sequence with a channel in the membrane.

Review Figure 12.15

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Chapter 12: From DNA to Protein: Genotype to Phenotype

Figure 12.15 –

Part 1

Figure 12.15 – Part 1

figure 12-15a.jpg

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Chapter 12: From DNA to Protein: Genotype to Phenotype

Figure 12.15 – Part 2

Figure 12.15 – Part 2

figure 12-15b.jpg

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Chapter 12: From DNA to Protein: Genotype to Phenotype

Posttranslational Events

Covalent modifications of proteins after translation include:

proteolysis – polypeptide chain is cut

Glycosylation – additions of sugars to proteins

Phosphorylation – add phosphate groups to protiens.

Review Figure 12.16

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Chapter 12: From DNA to Protein: Genotype to Phenotype

Figure 12.16

Figure 12.16

figure 12-16.jpg

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Chapter 12: From DNA to Protein: Genotype to Phenotype

Mutations: Heritable Changes in Genes

Mutations in DNA are often expressed as abnormal proteins.

However, the result may not be easily observable phenotypic changes.

Some mutations appear only under certain conditions, such as exposure to a certain environmental agent or condition.

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Chapter 12: From DNA to Protein: Genotype to Phenotype

Mutations: Heritable Changes in Genes

Point mutations (silent, missense, nonsense, or frame-shift) result from alterations in single base pairs of DNA.

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Chapter 12: From DNA to Protein: Genotype to Phenotype

Mutations: Heritable Changes in Genes

Chromosomal mutations (deletions, duplications, inversions, or translocations) involve large regions of a chromosome.

Review Figure 12.18

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Chapter 12: From DNA to Protein: Genotype to Phenotype

Figure 12.18

Figure 12.18

figure 12-18.jpg

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Chapter 12: From DNA to Protein: Genotype to Phenotype

Mutations: Heritable Changes in Genes

Mutations can be spontaneous or induced.

Spontaneous mutations occur because of instabilities in DNA or chromosomes.

Induced mutations occur when an outside agent damages DNA.

Review Figure 12.19

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Chapter 12: From DNA to Protein: Genotype to Phenotype

Figure 12.19 – Part 1

Figure 12.19 – Part 1

figure 12-19a.jpg

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Chapter 12: From DNA to Protein: Genotype to Phenotype

Figure 12.19 – Part

2Figure 12.19 – Part 2

figure 12-19b.jpg

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Chapter 12: From DNA to Protein: Genotype to Phenotype

One Gene, One Polypeptide

Certain hereditary diseases in humans have been found to be caused by the absence of certain enzymes.

Table 3-4 Phenylketonuria (PKU) is a recessive

disease caused by a defective allele for phenylalanine hydroxylase.

In the absence of the enzyme, phenylalanine in food is not broken down and accumulates.

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Chapter 12: From DNA to Protein: Genotype to Phenotype

PKU

At high concentrations phenylalanine is converted to phenylpyruvic acid.

Phenylpyyruvic acid interferes with the development of the nervous system.

Solution: An infant is put on a low phenylalanine diet so phenylalanine does not accumulate, no phenylpyruvic acid is made and the child develops normally.

Figure 3-28 These observations supported the one-gene,

one-polypeptide hypothesis.