Download - Chapter 7 Gene Expression and Control
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Chapter 7 Gene Expression and Control
7.1 Ricin and Your Ribosomes
The ability to make proteins is critical to all life processes
Seeds of the castor-oil plant contain the protein ricin, a deadly poison that inactivates ribosomes that assemble proteins
Ricin has been used by assassins, and is banned as a weapon under the Geneva Protocol
Seeds of the castor-oil plant
7.2 DNA, RNA, and Gene Expression
A gene is a DNA sequence that encodes an RNA or protein product in the sequence of its nucleotide bases (A, T, G, C)
In transcription, enzymes use the gene’s DNA sequence as a template to assemble a strand of messenger RNA (mRNA)
In translation, the protein-building information in mRNA is decoded into a sequence of amino acids
The result is a polypeptide chain that folds into a protein
sugar–phosphate backbone
base pair
nucleotide base
deoxyribonucleic acidDNA
ribonucleic acidRNA
DNA and RNA
Gene Expression
Gene expression involves transcription (DNA to mRNA), and translation (mRNA to protein)
Gene expression Process by which the information in a gene becomes
converted to an RNA or protein product
Proteins (enzymes) assemble other molecules and perform many functions that keep the cell alive
7.3 Transcription: DNA to RNA
During transcription, a strand of DNA acts as a template upon which a strand of RNA is assembled from nucleotides
Base-pairing rules in DNA replication apply to RNA synthesis in transcription, but RNA uses uracil in place of thymine
The enzyme RNA polymerase, not DNA polymerase, adds nucleotides to the end of a growing RNA strand
Base Pairing in Transcription
The Process of Transcription
In transcription, RNA polymerase binds to a promoter in the DNA near a gene
Polymerase moves along the DNA, unwinding the DNA so it can read the base sequence
RNA polymerase links RNA nucleotides in the order determined by the base sequence of the gene
The new mRNA is a copy of the gene from which it was transcribed
RNA polymerase
gene region
binding site in DNA
The enzyme RNA polymerase binds to a promoter in the DNA. The binding positions the polymerase near a gene. Only one of the two strands of DNA will be transcribed into RNA.
1
RNA polymerase binds to a promoter
RNA
DNA winding up
DNA unwinding
The polymerase begins to move along the gene and unwind the DNA. As it does, it links RNA nucleotides in the order specified by the nucleotide sequence of the template DNA strand. The DNA winds up again after the polymerase passes. The structure of the “opened” DNA at the transcription site is called a transcription bubble, after its appearance.
2
RNA nucleotides are linked
direction of transcription
Zooming in on the transcription bubble, we can see that RNA polymerasecovalently bonds successive nucleotides into an RNA strand. The new strand is an RNA copy of the gene.
3
RNA nucleotides are linked
Three Genes Being Transcribed
Many polymerases transcribe a gene region at the same time
RNA molecules DNA molecule
RNA Modifications
Eukaryotic cells modify their RNA before it leaves the nucleus Sequences that stay in the RNA are exons Introns are sequences removed during RNA processing
Exons can be spliced together in different combinations, so one gene may encode different proteins
After splicing, a tail of 50 to 300 adenines (poly-A tail) is added to the end of a new mRNA
gene
promoter exon intron exon intron exon
DNAtranscription
newly transcribed RNA
exon intron exon intron exon
exon exon exon
poly-A tail
finished mRNA
Post-transcriptional modification of RNA
ANIMATED FIGURE: Pre-mRNA transcript processing
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ANIMATED FIGURE: Gene transcription details
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ANIMATED FIGURE: Negative control of the lactose operon
7.4 RNA Players in Translation
Three types of RNA are involved in translation: mRNA, rRNA, and tRNA
mRNA produced by transcription carries protein-building information from DNA to the other two types of RNA for translation
mRNA and the Genetic Code
Information in mRNA consists of sets of three nucleotides (codons) that form “words” spelled with bases A, C, G, U
Sixty-four codons, most of which specify amino acids, constitute the genetic code
The sequence of three nucleotides in a base triplet determines which amino acid the codon specifies
The order of codons in mRNA determines the order of amino acids in the polypeptide that will be translated from it
Genetic Code
Twenty amino acids are encoded by the sixty-four codons in the genetic code
Some amino acids are specified by more than one codon
Other codons signal the beginning and end of a protein-coding sequence
Most organisms use the same code
The Genetic Code
a gene region in DNA
transcription
codon codon codon
mRNA
translation
methionine (met)
tyrosine (tyr)
serine (ser)
amino acid sequence
Correspondence between DNA, RNA, and proteins
rRNA and tRNA – the Translators
Ribosomes consist of two subunits of rRNA and structural proteins
Ribosomes and transfer RNAs (tRNA) interact to translate an mRNA into a polypeptide
tRNA has two attachment sites An anticodon base-pairs with an mRNA codon An attachment site binds to an amino acid specified by the
codon
Ribosome Structure
large subunit small subunit intact ribosome
+ =
anticodon
A) Icon and model of the tRNA that carries the amino acid tryptophan. Each tRNA’s anticodon is complementary to an mRNA codon. Each also carries the amino acid specified by that codon.
tRNA for Tryptophan
B) During translation, tRNAs dock at an intact ribosome (for clarity, only the small subunit is shown, in tan). Here, the anticodons of two tRNAs have base-pairedwith complementary codons on an mRNA (red).
tRNAs dock at a ribosome
ANIMATED FIGURE: Structure of a ribosome
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7.5 Translating the Code: RNA to Protein
Translation (second part of protein synthesis) occurs in the cytoplasm of all cells: mRNA is transcribed in the nucleus In the cytoplasm a small ribosomal subunit binds to mRNA Initiator tRNA base-pairs with the first mRNA codon Large ribosomal subunit joins the small subunit Ribosome assembles a polypeptide chain Translation ends when the ribosome encounters a stop
codon
Translation in Eukaryotes
Transcription
ribosome subunitsRNA transport
tRNA
1
Convergence of RNAs
mRNATranslation
polypeptide
2
3
4
Ribosome assembles a polypeptide chain
Ribosome assembles a polypeptide chain
Ribosome assembles a polypeptide chain
ANIMATED FIGURE: Translation
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7.6 Mutated Genes and Their Products
Mutations are permanent changes in the nucleotide sequence of DNA, which may alter a gene product
A mutation that changes a gene’s product may have harmful effects
Example: Mutations that affect the proteins in hemoglobin reduce blood’s ability to carry oxygen
Types of Mutations
Base-pair substitution Type of mutation in which a single base-pair changes Example: Sickle cell anemia
Mutations that shift the reading frame of the mRNA codons: Deletion of one or more base pairs Insertion of one or more base pairs Example: Beta thalassemia
A) Hemoglobin, an oxygen-binding protein in red blood cells. This protein consists of four polypeptides: two alpha globins (blue) and two beta globins (green). Each globin forms a pocket that cradles a type of cofactor called a heme (red ). Oxygen gas binds to the iron atom at the center of each heme.
Mutations in Hemoglobin
B) Part of the DNA (blue), mRNA (brown), and amino acid sequence (green) of human beta globin. Numbers indicate the position of the nucleotide in the coding sequence of the mRNA.
Mutations in Hemoglobin
C) A base-pair substitution replaces a thymine with an adenine. When the altered mRNA is translated, valine replaces glutamic acid as the sixth amino acid of the polypeptide. Hemoglobin with this form of beta globin is called HbS, or sickle hemoglobin.
Mutations in Hemoglobin
D) A deletion of one nucleotide causes the reading frame for the rest of the mRNA to shift. The protein translated from this mRNA is too short and does not assemble correctly into hemoglobin molecules. The result is beta thalassemia,in which a person has an abnormally low amount of hemoglobin.
Mutations in Hemoglobin
E) An insertion of one nucleotide causes the reading frame for the rest of the mRNA to shift. The protein translated from this mRNA is too short and does not assemble correctly into hemoglobin molecules. As in D, the outcome is beta thalassemia.
Mutations in Hemoglobin
glutamic acid valine
A) A base-pair substitution results in the abnormal beta globin chain of sickle hemoglobin (HbS). The sixth amino acid in such chains is valine, not glutamic acid. The difference causes HbS molecules to form rod-shaped clumps that distort normally round blood cells into sickle shapes.
Sickle-Cell Anemia: A Base-Pair Substitution
sickled cell
normal cell
B) Left, the sickled cells clog small blood vessels, causing circulatory problems that result in damage to many organs. Destruction of the cells by the body’s immune system results in anemia. Right, Tionne “T-Boz” Watkins of the music group TLC is a celebrity spokesperson for the Sickle Cell Disease Association of America. She was diagnosed with sickle-cell anemia as a child.
Sickle-Cell Anemia
What Causes Mutations?
Most mutations result from unrepaired DNA polymerase errors during DNA replication
Some natural and synthetic chemicals cause mutations in DNA (example: cigarette smoke)
Insertion mutations may be caused by transposable elements, which move within or between chromosomes
ANIMATED FIGURE: Base-pair substitution
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ANIMATION: Deletion
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ANIMATION: Frameshift mutation
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ANIMATED FIGURE: Sickle-cell anemia
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ANIMATED FIGURE: Controls of eukaryotic gene expression
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ANIMATION: X-chromosome inactivation
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7.7 Eukaryotic Gene Controls
All cells in your body carry the same DNA
Some genes are transcribed by all cells, but most cells are specialized (differentiated) to use only certain genes
Which genes are expressed at a given time depends on the type of cell and conditions
Cell Differentiation
Cells differentiate when they start expressing a unique subset of their genes – controls over gene expression are the basis of differentiation
Differentiation The process by which cells become specialized Occurs as different cell lineages begin to express different
subsets of their genes
Controlling Gene Expression
Controlling gene expression is critical for normal development and function of a eukaryotic body
All steps between transcription and delivery of gene product are regulated
Transcription factor Protein that influences transcription by binding to DNA
Master Genes
Master gene Gene encoding a product that affects the expression of
many other genes Controls an intricate task such as eye formation
Homeotic gene Type of master gene that controls formation of specific
body parts during development
Studying Homeotic Genes
Researchers study the function of a homeotic gene by altering its expression – by introducing a mutation or deleting it entirely (gene knockout) Examples: antennapedia, dunce, tinman, groucho
Many homeotic genes are interchangeable among species Example: eyeless gene in flies and PAX 6 gene in humans
A) A transcription factor—the protein product (gold )of an insect gene called antennapedia attaches to apromoter sequence in a fragment of DNA. In cells ofa fly embryo, the binding starts a cascade of cellularevents that results in the formation of a leg.
Example of gene control
B) Antennapedia is a homeotic gene whose expression in embryonic tissues of the insect thorax causes legs to form. A mutation that causes antennapedia to be expressed in the embryonic tissues of the head causes legs to form there too (left). Compare the head of the normal fly on the right.
Example of gene control
Gene Knockout Experiment: Eyeless
A) A fruit fly with a mutation in its eyeless gene develops with no eyes.
B) Compare the large, round eyes of a normal fruit fly.
C) Eyes form wherever the eyeless gene is expressed in fly embryos. Abnormal expression of the eyeless gene in this fly caused extra eyes to develop on its head and also on its wings.
PAX6 Gene Function
In humans and many other animals, the PAX6 gene affects eye formation
D) Humans, mice, squids, and other animals have a gene called PAX6. In humans, PAX6 mutations result in missing irises, a condition called aniridia (left ). Compare a normal iris (right ). PAX6 is so similar to eyeless that it triggers eye development when expressed in fly embryos.
Sex Chromosome Genes
In mammals, males have only one X chromosome – females have two, but one is tightly condensed into a Barr body and not expressed
According to the theory of dosage compensation, X chromosome inactivation equalizes expression of X chromosome genes between the sexes
X Chromosome Inactivation
A) Barr bodies. The photo on the left shows the nucleus of five XX cells. Inactivated X chromosomes—Barr bodies— appear as red spots. Compare the nucleus of two XY cells in the photo on the right
The Y Chromosome
The human X chromosome carries 1,336 genes
The human Y chromosome carries 307 genes, including SRY— the master gene for male sex determination Triggers formation of testes Testosterone produced by testes controls formation of
male secondary traits
Absence of SRY gene in females triggers development of ovaries, female characteristics
SRY gene expressed no SRY present
penis
vaginal opening
birth approaching
B) An early human embryo appears neither male nor female. SRY gene expression determines whether male reproductive organs develop.
Development of Human Reproductive Organs
Epigenetics
Transcription is affected by chromosome structure
Modifications that suppress gene expression: Adding a methyl group (CH3) to a histone protein Direct methylation of DNA nucleotides
Once a particular nucleotide has become methylated, it usually stays methylated in all of the cell’s descendants
Environmental factors, including the chemicals in cigarette smoke, add more methyl groups
Methyl group attached to a DNA nucleotide
Epigenetics
Methylation of parental chromosomes is normally “reset” in the first cell of the new individual
All parental methyl groups are not removed, so some methylations can be passed to future offspring
Boys are affected by lifestyle of individuals in the father’s line; girls, by individuals in the mother’s line
Heritable changes in gene expression that are not due to changes in underlying DNA sequence are epigenetic
An epigenetic effect
Grandsons of boys who endured a winter of famine tend to live longer than grandsons of boys who overate at the same age
7.8 Ricin and Your Ribosomes (revisited)
Ricin is a ribosome-inactivating protein (RIP)
Toxic RIPs, including ricin, have one polypeptide chain that binds tightly to carbohydrates on plasma membranes
Once inside the cell, a second polypeptide inactivates the ribosomes, and the cell quickly dies
Other RIPs include Shiga toxin (dysentery) and E. coli O157:H7 (food poisoning)
Some RIPs
ricin Shiga toxin E. coli enterotoxin
Digging Into Data: Paternal Grandmother’s Food Supply and Infant Mortality