Gene Expression + Genetic Code CH 9

Major chemical differences between RNA and DNA

RNA has ribose sugar instead of deoxyribose, uracil (UU) instead of thymine (TT), and is predominantly single-stranded with the capacity to form intramolecular secondary structures.

Central Dogma of Molecular Biology

The standard pathway of genetic information transfer common to all living cells: DNA→RNA→Protein, carried out by transcription and translation.

Triplet codon organization of the genetic code

A continuous sequence of 3 nucleotide bases specifying a single amino acid, yielding 4³=64 possible combinations to encode 20 standard amino acids.

Degeneracy vs. unambiguous nature of the genetic code

The code is degenerate because multiple distinct triplet codons can encode the same amino acid, but unambiguous because any single codon specifies only one unique amino acid.

Standard translation start codon and stop codons

Translation initiates at AUG (encoding methionine) and terminates at one of three nonsense stop codons: UAA, UAG, or UGA.

Prokaryotic transcription initiation

RNA polymerase holoenzyme recognizes and binds a promoter sequence near the gene start via its sigma (σ) subunit, unwinding the DNA helix to form an open promoter complex.

Transcription elongation directionality and substrate usage

RNA polymerase reads the template DNA strand in the 3′→5′ direction while synthesizing the nascent RNA strand in the 5′→3′ direction using ribonucleoside triphosphates (NTPsNTPs).

Prokaryotic transcription termination mechanism

RNA polymerase transcribes a terminator sequence that forms a hairpin loop (stem-loop) via intramolecular base pairing, triggering the release of RNA polymerase and the newly formed transcript.

Key post-transcriptional modifications of eukaryotic pre-mRNA

Addition of a 5′ methylated guanylate cap, addition of a 3′poly-A tail, and RNA splicing to remove non-coding introns and ligate coding exons.

Role of aminoacyl-tRNA synthetases

Enzymes that covalently attach a specific amino acid to the 3′ hydroxyl end of its corresponding tRNA using energy from ATP hydrolysis, producing a charged tRNA.

Wobble hypothesis mechanism

Flexibility in base pairing between the 5′5′ base of the tRNA anticodon and the 3′3′ base of the mRNA codon, allowing one tRNA to recognize more than one codon specifying the same amino acid.

Codon base pairing for an anticodon with 5′ G

Under wobble rules, a guanine at the 5′ position of a tRNA anticodon can base pair with either uracil (UU) or cytosine (CC) at the 3′ position of the mRNA codon.

Three stages of mRNA translation on the ribosome

1. Initiation: assembly of ribosomal subunits and initiator tRNA at the start codon;

2. Elongation: peptidyl transferase catalyzes peptide bond formation as tRNAs cycle through A, P, and E sites;

3. Termination: release factors recognize stop codons and release the peptide.

Silent mutation effect on protein structure

A single nucleotide substitution that changes a codon to a synonymous codon encoding the same amino acid, leaving the final polypeptide sequence unaltered.

Missense mutation effect on protein structure

A single nucleotide change that replaces 1 amino acid with another, which may alter protein conformation and functional activity.

Nonsense mutation effect on protein structure

A nucleotide substitution that changes an amino acid codon into a premature stop codon (UAA, UAG, or UGA), yielding a truncated and often nonfunctional polypeptide.

Frameshift mutation mechanism and consequence

The insertion or deletion of nucleotides not in multiples of three within a coding region, which alters the triplet reading frame downstream and changes all subsequent amino acids until a premature stop codon is reached.

Null (amorphic) allele

A loss-of-function allele that completely eliminates gene product activity (e.g., deletion of an entire gene), typically behaving as recessive to wild type.

Hypomorphic allele

A loss-of-function allele that produces either reduced levels of a gene product or a protein with weak, detectable residual activity, usually recessive to wild type.

Hypermorphic allele

A gain-of-function allele that produces an increased quantity of gene product or a constitutively active/hyperactive protein, typically acting dominantly (e.g., FGFR3 in achondroplasia).

Neomorphic allele

A dominant gain-of-function allele that imparts a novel biochemical function or directs ectopic gene expression in an abnormal tissue or developmental time point (e.g., Antennapedia in flies).

Antimorphic (dominant negative) allele

An allele whose mutant product directly interferes with or antagonizes the activity of the wild-type protein, frequently by forming inactive multimeric protein complexes.