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What is the fundamental relationship between genes and proteins?
What is the fundamental relationship between genes and proteins?
Genes provide the instructions for building proteins.
What is the role of enzymes in the context of gene expression?
What is the role of enzymes in the context of gene expression?
Enzymes catalyze specific chemical reactions, and genes dictate phenotypes through these enzymes.
What did Archibald Garrod suggest about genes and phenotypes?
What did Archibald Garrod suggest about genes and phenotypes?
He proposed that genes dictate phenotypes through enzymes that catalyze specific chemical reactions.
What experimental approach did George Beadle and Edward Tatum use in their research on Neurospora?
What experimental approach did George Beadle and Edward Tatum use in their research on Neurospora?
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What is the "one gene-one enzyme" hypothesis?
What is the "one gene-one enzyme" hypothesis?
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What is the bridge between genes and the proteins they code for?
What is the bridge between genes and the proteins they code for?
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What are the two main stages of gene expression?
What are the two main stages of gene expression?
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What type of RNA is produced during transcription?
What type of RNA is produced during transcription?
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What process involves the synthesis of a polypeptide chain?
What process involves the synthesis of a polypeptide chain?
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What are the sites of translation?
What are the sites of translation?
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In prokaryotes, translation of mRNA can begin before transcription is finished.
In prokaryotes, translation of mRNA can begin before transcription is finished.
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In a eukaryotic cell, transcription and translation occur in the same compartment.
In a eukaryotic cell, transcription and translation occur in the same compartment.
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What modification do eukaryotic RNA transcripts undergo before they are translated?
What modification do eukaryotic RNA transcripts undergo before they are translated?
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What is the central dogma of molecular biology?
What is the central dogma of molecular biology?
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What type of code is used to assemble amino acids into proteins?
What type of code is used to assemble amino acids into proteins?
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How many nucleotides make up a codon?
How many nucleotides make up a codon?
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During transcription, which strand of DNA is used as a template for RNA synthesis?
During transcription, which strand of DNA is used as a template for RNA synthesis?
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In which direction are codons read during translation?
In which direction are codons read during translation?
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What are the three stop codons in the genetic code?
What are the three stop codons in the genetic code?
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The genetic code is ambiguous.
The genetic code is ambiguous.
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What is meant by the "reading frame" in the context of the genetic code?
What is meant by the "reading frame" in the context of the genetic code?
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Why is the universality of the genetic code significant?
Why is the universality of the genetic code significant?
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What catalyzes RNA synthesis?
What catalyzes RNA synthesis?
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What is the name of the DNA sequence where RNA polymerase attaches?
What is the name of the DNA sequence where RNA polymerase attaches?
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What is the name of the DNA sequence that signals the end of transcription in bacteria?
What is the name of the DNA sequence that signals the end of transcription in bacteria?
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What are the three stages of transcription?
What are the three stages of transcription?
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What are transcription factors?
What are transcription factors?
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What is a TATA box?
What is a TATA box?
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RNA polymerase moves along the DNA in the 3' to 5' direction during elongation.
RNA polymerase moves along the DNA in the 3' to 5' direction during elongation.
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Where are nucleotides added to the growing RNA molecule?
Where are nucleotides added to the growing RNA molecule?
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The mechanisms of termination are the same in bacteria and eukaryotes.
The mechanisms of termination are the same in bacteria and eukaryotes.
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What is RNA processing?
What is RNA processing?
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What is the 5' cap?
What is the 5' cap?
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What is the poly-A tail?
What is the poly-A tail?
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What are introns?
What are introns?
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What is RNA splicing?
What is RNA splicing?
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What are spliceosomes?
What are spliceosomes?
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What are ribozymes?
What are ribozymes?
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What is alternative RNA splicing?
What is alternative RNA splicing?
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What are protein domains?
What are protein domains?
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Exon shuffling can lead to the evolution of new proteins.
Exon shuffling can lead to the evolution of new proteins.
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What is the role of transfer RNA (tRNA) in translation?
What is the role of transfer RNA (tRNA) in translation?
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What is the role of the ribosome in translation?
What is the role of the ribosome in translation?
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What are the three binding sites on a ribosome?
What are the three binding sites on a ribosome?
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What is the role of initiation factors in translation?
What is the role of initiation factors in translation?
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What is the role of release factors in translation?
What is the role of release factors in translation?
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What is a polyribosome (polysome)?
What is a polyribosome (polysome)?
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Translation is always sufficient to produce a functional protein.
Translation is always sufficient to produce a functional protein.
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What are the two populations of ribosomes in cells?
What are the two populations of ribosomes in cells?
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What is a signal peptide?
What is a signal peptide?
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What is a signal-recognition particle (SRP)?
What is a signal-recognition particle (SRP)?
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What is a mutation?
What is a mutation?
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What is a point mutation?
What is a point mutation?
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What is a missense mutation?
What is a missense mutation?
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What is a frameshift mutation?
What is a frameshift mutation?
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Archaea are eukaryotes that share many features of gene expression with bacteria.
Archaea are eukaryotes that share many features of gene expression with bacteria.
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Bacteria and eukaryotes differ in their RNA polymerases, termination of transcription, and ribosomes.
Bacteria and eukaryotes differ in their RNA polymerases, termination of transcription, and ribosomes.
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In bacteria, transcription and translation are separated by the nuclear envelope.
In bacteria, transcription and translation are separated by the nuclear envelope.
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In archaea, transcription and translation are likely coupled.
In archaea, transcription and translation are likely coupled.
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What is a gene?
What is a gene?
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Study Notes
Chapter 17: From Gene to Protein
- The information content of DNA is in the form of specific sequences of nucleotides.
- Inherited DNA leads to specific traits by dictating protein synthesis.
- Proteins link genotype to phenotype.
- Gene expression, the process by which DNA directs protein synthesis, involves two stages: transcription and translation.
- In 1902, Archibald Garrod suggested that genes dictate phenotypes through enzymes that catalyze chemical reactions. He theorized inherited disease symptoms stem from an inability to synthesize specific enzymes.
Concept 17.1: Genes Specify Proteins Via Transcription and Translation
- How was the fundamental relationship between genes and proteins discovered?
Evidence from the Study of Metabolic Defects
- In 1902, British physician Archibald Garrod first suggested that genes dictate phenotypes through enzymes that catalyze specific chemical reactions.
- He thought inherited disease symptoms reflected an inability to synthesize a certain enzyme.
- Linking genes to enzymes required understanding that cells synthesize and degrade molecules in a series of steps (a metabolic pathway).
Nutritional Mutants in Neurospora: Scientific Inquiry
- George Beadle and Edward Tatum exposed bread mold to X-rays, creating mutants. These mutants couldn't survive on minimal media.
- Using crosses, they and their coworkers identified three classes of arginine-deficient mutants, each lacking a different enzyme necessary for synthesizing arginine.
- They developed the one gene-one enzyme hypothesis.
The Products of Gene Expression: A Developing Story
- Some proteins are not enzymes; researchers later revised the hypothesis: one gene-one protein.
- Many proteins are composed of several polypeptides, each of which has its own gene.
- Beadle and Tatum's hypothesis is now restated as the one gene-one polypeptide hypothesis.
- Gene products are commonly referred to as proteins rather than polypeptides.
Basic Principles of Transcription and Translation
- RNA bridges the gap between genes and the proteins they code for.
- Transcription is the synthesis of RNA under the direction of DNA, producing messenger RNA (mRNA).
- Translation is the synthesis of a polypeptide, using mRNA information; ribosomes are the sites of translation.
- In prokaryotes, translation of mRNA can begin before transcription has finished.
- In eukaryotic cells, the nuclear envelope separates transcription from translation; eukaryotic RNA transcripts undergo processing.
A Primary Transcript
- A primary transcript is the initial RNA transcript from any gene prior to processing.
The Central Dogma
- The central dogma is the concept that cells are governed by a cellular chain of command: DNA → RNA → protein.
The Genetic Code
- How are the instructions for assembling amino acids into proteins encoded into DNA?
- There are 20 amino acids in proteins, but only four nucleotide bases in DNA.
- How many nucleotides correspond to an amino acid?
Codons: Triplets of Nucleotides
- The flow of information from gene to protein is based on a triplet code. This consists a series of nonoverlapping, three-nucleotide words.
- The words of a gene are transcribed into complementary nonoverlapping three-nucleotide words of mRNA.
- These words are then translated into a chain of amino acids, forming a polypeptide.
Transcription
- During transcription, one of the two DNA strands (the template strand) provides a template for ordering the sequence of complementary nucleotides in an RNA transcript.
- The template strand is always the same strand for a given gene.
- During translation, mRNA base triplets (codons) are read in the 5' to 3' direction.
Cracking the Code
- All 64 codons were deciphered by the mid-1960s.
- Of the 64 triplets, 61 code for amino acids; 3 triplets are "stop" signals to end translation.
- The genetic code is redundant—more than one codon may specify a particular amino acid, but not ambiguous; no codon specifies more than one amino acid.
- Codons must be read in the correct reading frame for the specified polypeptide to be produced.
Evolution of the Genetic Code
- The genetic code is nearly universal, shared by all organisms from bacteria to complex animals.
- Genes can be transcribed and translated after being transplanted from one species to another.
Concept 17.2 Transcription: A Closer Look
- Transcription is the first stage of gene expression.
Molecular Components of Transcription
- RNA synthesis is catalyzed by RNA polymerase, which pries the DNA strands apart and hooks together RNA nucleotides.
- The RNA is complementary to the DNA template strand.
- RNA synthesis follows the same base-pairing rules as DNA, but uracil substitutes for thymine.
Molecular Components of Transcription (continued)
- The DNA sequence where RNA polymerase attaches is called the promoter. In bacteria, the sequence signaling the end of transcription is called the terminator.
- The stretch of DNA that is transcribed is called a transcription unit.
Synthesis of an RNA Transcript
- The three stages of transcription: initiation, elongation, and termination.
RNA Polymerase Binding and Initiation of Transcription
- Promoters signal the transcriptional start point and usually extend several dozen nucleotide pairs upstream of the start point.
- Transcription factors mediate the binding of RNA polymerase and the initiation of transcription.
- The completed assembly of transcription factors and RNA polymerase II bound to a promoter is called a transcription initiation complex.
- A promoter called a TATA box is crucial in forming the initiation complex in eukaryotes.
Elongation of the RNA Strand
- As RNA polymerase moves along the DNA, it untwists the double helix, 10 to 20 bases at a time.
- Transcription progresses at a rate of 40 nucleotides per second in eukaryotes.
- A gene can be transcribed simultaneously by several RNA polymerases.
- Nucleotides are added to the 3' end of the growing RNA molecule.
Termination of Transcription
- The mechanisms of termination are different in bacteria and eukaryotes.
- In bacteria, the polymerase stops transcription at the end of the terminator, and the mRNA can be translated without further modification.
- In eukaryotes, RNA polymerase II transcribes a polyadenylation signal sequence; the RNA transcript is released 10–35 nucleotides past this sequence.
Concept 17.3: Eukaryotic Cells Modify RNA After Transcription
- Enzymes in the eukaryotic nucleus modify pre-mRNA (RNA processing) before the genetic messages are dispatched to the cytoplasm.
- During RNA processing, both ends of the primary transcript are usually altered.
- Usually, some interior parts of the molecule are cut out, and other parts are spliced together.
Alteration of mRNA Ends
- Each end of a pre-mRNA molecule is modified in a particular way.
- The 5' end receives a modified nucleotide 5' cap.
- The 3' end gets a poly-A tail.
- These modifications facilitate export, protect mRNA from hydrolytic enzymes, and help ribosomes attach.
Split Genes and RNA Splicing
- Most eukaryotic genes and their RNA transcripts have long noncoding stretches of nucleotides that lie between coding regions called introns.
- The other regions are exons because they are eventually expressed and usually translated into amino acid sequences.
- RNA splicing removes introns and joins exons, forming a continuous coding sequence in the mRNA.
Spliceosomes
- In some cases, RNA splicing is carried out by spliceosomes.
- Spliceosomes consist of a variety of proteins and several small nuclear ribonucleoproteins (snRNPs) that recognize the splice sites.
Ribozymes
- Ribozymes are catalytic RNA molecules that function as enzymes and can splice RNA.
- The discovery of ribozymes rendered obsolete the belief that all biological catalysts were proteins.
Properties of RNA that Enable it to Function as an Enzyme
- RNA can form a three-dimensional structure due to its ability to base-pair with itself.
- Some bases in RNA contain functional groups that can participate in catalysis.
- RNA may hydrogen-bond with other nucleic acid molecules.
The Functional and Evolutionary Importance of Introns
- Some introns contain sequences that may regulate gene expression.
- Some genes can encode more than one kind of polypeptide, depending on which segments are treated as exons during splicing (alternative RNA splicing).
- Consequently, the number of different proteins an organism can produce can be much greater than its number of genes.
Proteins and Domains
- Proteins often have a modular architecture consisting of discrete regions called domains.
- In many cases, different exons code for the different domains in a protein.
- Exon shuffling may result in the evolution of new proteins.
Concept 17.4 Translation: A Closer Look
- Genetic information flows from mRNA to protein through the process of translation.
Molecular Components of Translation
- A cell translates an mRNA message into protein with the help of transfer RNA (tRNA).
- tRNA transfers amino acids to the growing polypeptide in the ribosome.
- Translation is a complex process in terms of its biochemistry and mechanics.
The Structure and Function of Transfer RNA (tRNA)
- tRNA molecules are not identical; each carries a specific amino acid on one end and has an anticodon on the other.
- The anticodon base-pairs with a complementary codon on mRNA.
tRNA Structure
- tRNA consists of a single RNA strand that is only about 80 nucleotides long.
- When flattened into one plane, a tRNA molecule resembles a cloverleaf.
Accurate Translation Requires Two Steps:
- First: a correct match between a tRNA and an amino acid, done by the enzyme aminoacyl-tRNA synthetase.
- Second: a correct match between the tRNA anticodon and an mRNA codon.
Wobble
- Flexible pairing at the third base of a codon is called wobble and allows some tRNAs to bind to more than one codon.
Ribosomes
- Ribosomes facilitate specific coupling of tRNA anticodons with mRNA codons in protein synthesis.
- The two ribosomal subunits (large and small) consist of proteins and ribosomal RNA (rRNA).
- Bacterial and eukaryotic ribosomes are somewhat similar but have significant differences; some antibiotic drugs specifically target bacterial ribosomes, not eukaryotic ones.
Building a Polypeptide
- The three stages of translation are initiation, elongation, and termination.
- All three stages require protein factors that aid in the translation process.
Ribosome Association and Initiation of Translation
- The initiation stage of translation brings together mRNA, a tRNA with the first amino acid, and the two ribosomal subunits.
- First, a small ribosomal subunit binds with mRNA and a special initiator tRNA.
- Then, the small subunit moves along the mRNA until it reaches the start codon (AUG).
- Proteins called initiation factors bring in the large subunit, completing the translation initiation complex.
Elongation of the Polypeptide Chain
- During elongation, amino acids are added one by one to the preceding amino acid at the C-terminus of the growing chain.
- Each addition involves proteins called elongation factors and occurs in three steps: codon recognition, peptide bond formation, and translocation.
- Translation proceeds along the mRNA in a 5' to 3' direction.
Termination of Translation
- Termination occurs when a stop codon in the mRNA reaches the A site of the ribosome.
- The A site accepts a protein called a release factor.
- The release factor causes the addition of a water molecule instead of an amino acid.
- This reaction releases the polypeptide, and the translation assembly comes apart.
Polyribosomes
- A number of ribosomes can translate a single mRNA simultaneously, forming a polyribosome or polysome.
- Polyribosomes enable a cell to make many copies of a polypeptide very quickly.
Completing and Targeting the Functional Protein
- Often, translation is not sufficient to make a functional protein.
- Polypeptide chains are modified after translation or targeted to specific sites in the cell.
Protein Folding and Post-Translational Modifications
- During and after synthesis, a polypeptide chain spontaneously coils and folds into its three-dimensional shape.
- Proteins may also require post-translational modifications before doing their job.
- Some polypeptides are activated by enzymes that cleave them.
- Other polypeptides come together to form the subunits of a protein.
Targeting Polypeptides to Specific Locations
- Two populations of ribosomes are evident in cells: free ribosomes (in the cytosol) and bound ribosomes (attached to the ER).
- Free ribosomes mostly synthesize proteins that function in the cytosol.
- Bound ribosomes make proteins of the endomembrane system and proteins that are secreted from the cell.
- Ribosomes are identical and can switch from free to bound.
Polypeptide Synthesis
- Polypeptide synthesis always begins in the cytosol.
- Synthesis finishes in the cytosol unless the polypeptide signals the ribosome to attach to the ER.
- Polypeptides destined for the ER or secretion are marked by a signal peptide.
Signal-Recognition Particle (SRP)
- A signal-recognition particle (SRP) binds to the signal peptide.
- The SRP brings the signal peptide and its ribosome to the ER.
Concept 17.5: Mutations of One or a Few Nucleotides Can Affect Protein Structure and Function
- Mutations are changes in the genetic material of a cell or virus.
- Point mutations are chemical changes in just one base pair of a gene.
- The change of a single nucleotide in the template strand can lead to the production of an abnormal protein.
Point Mutations
- Point mutations within a gene can be divided into two general categories: nucleotide-pair substitutions and one or more nucleotide-pair insertions or deletions.
Substitutions:
- A nucleotide-pair substitution replaces one nucleotide and its partner with another pair of nucleotides.
- Silent mutations have no effect on the amino acid sequence.
- Missense mutations still code for an amino acid, but not the correct one.
- Nonsense mutations change an amino acid codon into a stop codon, virtually always leading to a nonfunctional protein.
Insertions and Deletions
- Insertions and deletions are additions or losses of nucleotide pairs in a gene.
- These mutations have a disastrous effect on the resulting protein more often than substitutions do.
- An insertion or deletion of nucleotides may alter the reading frame, producing a frameshift mutation.
Mutagens
- Spontaneous mutations can occur during DNA replication, recombination, or repair.
- Mutagens are physical or chemical agents that can cause mutations.
Concept 17.6: While Gene Expression Differs…
- Archaea are prokaryotes but share many features of gene expression with eukaryotes.
Comparing Gene Expression in Bacteria, Archaea, and Eukarya
- Bacteria and eukarya differ in their RNA polymerases, termination of transcription, and ribosomes. Archaea tend to resemble eukaryotes in these aspects.
- Bacteria can simultaneously transcribe and translate the same gene.
- In eukaryotes, transcription and translation are separated by the nuclear envelope.
- In archaea, transcription and translation are likely coupled.
What Is a Gene? Revisiting the Question
- The idea of the gene has evolved through the history of genetics.
- We have considered a gene as a discrete unit of inheritance, a region of specific nucleotide sequence in a chromosome, and a DNA sequence that codes for a specific polypeptide chain.
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Description
Explore the critical relationship between genes and protein synthesis as laid out in Chapter 17. This chapter delves into how DNA sequences dictate traits through the processes of transcription and translation, and discusses historical insights from Archibald Garrod on metabolic defects. Test your understanding of these fundamental concepts.