Molecular Genetics: Gene Regulation and Mutations

Comprehensive vocabulary flashcards covering bacterial and eukaryotic gene regulation (lac and trp operons, GAL4 system, chromatin remodeling, histone modifications, RNAi) and molecular mechanisms of genetic mutations (transitions, transversions, point mutations, indels, and repair).

Operon

A functional genetic unit found in prokaryotes consisting of two or more genes that share a single promoter and are transcribed together into a single polycistronic mRNA.

Structure of the lac Operon

A coordinated genetic unit in E. coli composed of regulatory sequences—the promoter (lac P) and operator (lac O)—along with three structural genes: lac Z (encoding $\beta$-galactosidase), lac Y (encoding permease), and lac A.

lac O^c Mutation

A cis-acting constitutive operator mutation that prevents the repressor (LacI) protein from binding, resulting in continuous transcription of downstream structural genes that takes precedence over super-repressor mutations (LacI^s).

lac I^s Mutation (Super Repressor)

A trans-acting mutation in the repressor gene producing an altered repressor protein that permanently locks onto the operator (lac O), rendering it insensitive to inducer and preventing operon transcription.

Lac Repressor Protein (LacI)

A negative regulatory protein that binds to the lac operator (lac O) to inhibit transcription; when bound by the inducer (allolactose), it undergoes a conformational change that loosens its binding to allow transcription.

Allolactose

The inducer molecule of the lac operon that binds directly to the LacI repressor protein, causing the repressor to release from the operator and allow RNA polymerase to proceed with transcription.

Partial Diploid

A bacterium (such as E. coli) that is normally haploid but carries a second copy of a specific subset of genes on an $F'$ plasmid, commonly utilized to distinguish cis-acting elements from trans-acting factors.

Catabolite Activator Protein (CAP)

A positive regulatory protein that complexes with $\text{cAMP}$ under low glucose conditions; the CAP-$\text{cAMP}$ complex binds to the promoter to stimulate RNA polymerase binding and promote high-level transcription.

Adenylate Cyclase

An enzyme that converts $\text{ATP}$ to $\text{cAMP}$; its activity is inhibited when glucose levels are high and permitted when glucose levels fall, triggering $\text{cAMP}$ accumulation for CAP activation.

Structure of the trp Operon

A repressible biosynthetic operon comprising a promoter, an operator, a leader region (trpL) containing an attenuator sequence, and five structural genes: trpE, trpD, trpC, trpB, and trpA.

trpR Repressor

A regulatory repressor protein that binds with tryptophan to undergo an allosteric shift, enabling it to attach to the trp operator and repress operon transcription.

Attenuation (trp Operon)

A transcriptional regulatory mechanism in prokaryotes where high cellular tryptophan levels allow ribosome translation through trpL, permitting regions 3 and 4 of the mRNA transcript to pair into a terminator hairpin flanked by poly-U, which prematurely detaches RNA polymerase.

Anti-terminator Hairpin

A secondary mRNA stem-loop structure formed by the base-pairing of regions 2 and 3 in trpL when tryptophan concentration is low and the ribosome stalls at tandem Trp codons; this prevents region 3 from pairing with region 4, allowing transcription to continue.

Positive Regulation

A mechanism of gene regulation in which an activator protein binds to DNA to stimulate, initiate, or increase the transcription of target genes.

Negative Regulation

A mechanism of gene regulation in which a repressor protein binds to regulatory DNA (such as an operator) to block or shut off transcription.

Enhancer

A eukaryotic regulatory DNA sequence that stimulates transcription by binding specific transcription factors (activators) and looping across distance to interact directly with the core promoter complex.

CpG Island

A region of eukaryotic DNA rich in cytosine-guanine dinucleotide repeats, commonly found within promoter areas, whose methylation causes gene silencing by blocking transcription factor binding.

GAL4

A trans-acting transcription factor in yeast that binds to upstream activating sequences ($\text{UAS}_{\text{GAL}}$) to drive the expression of galactose-metabolizing enzymes.

GAL80 Repression

The mechanism whereby the GAL80 repressor protein binds directly to the activation domain/allosteric site of GAL4, preventing GAL4 from interacting with the basal transcription factor complex (TFIID) and keeping galactose gene transcription off.

GAL3 Activation

The induction mechanism in yeast where galactose and $\text{ATP}$ bind to GAL3, prompting GAL3 to bind and sequester the GAL80 repressor; this allows GAL4 to bind the basal transcription factor complex (TFIID) and activate transcription.

Combinatorial Control

The regulatory principle in eukaryotes where specific combinations, configurations, and concentrations of multiple regulatory elements and proteins (transcription factors, enhancers, co-activators) interact to coordinate precise spatial and temporal gene expression.

Histone

A family of basic, positively charged proteins located in eukaryotic nuclei that act as structural spools around which DNA winds to form nucleosomes.

Chromatin Remodeling

The active repositioning or sliding of nucleosomes along DNA driven by the phosphorylation of a Chromatin Remodeling Complex (CRC) protein, exposing previously inaccessible promoter regions to transcription factors and RNA polymerase.

Histone Acetylation

The enzymatic transfer of acetyl groups onto lysine or arginine residues on histone tails by histone acetyltransferases (HATs), neutralizing positive charges to generate an open chromatin state that activates transcription.

Histone Methylation

The addition of methyl groups to lysine or arginine residues on histone tails by methyltransferases, an epigenetic modification that can activate or repress transcription depending on location, but most frequently represses expression.

Flowering Locus C (FLC)

A gene in Arabidopsis encoding a repressor of flowering whose locus is open and actively transcribed in warm autumn weather to prevent premature flowering, and deacetylated/silenced following prolonged cold exposure in winter to permit spring flowering.

RNA Interference (RNAi)

A post-transcriptional gene regulatory mechanism mediated by small RNAs: siRNAs bind with $100\%$ complementarity to degrade target mRNAs, while miRNAs bind with partial complementarity to repress mRNA translation.

Genetic Neighborhood

A localized chromosomal cluster of genes and linked regulatory elements that share a functional domain and whose transcriptional access is coordinately regulated by shared local chromatin structure.

Germline Mutation

A mutation occurring in reproductive germ cells (gametes) that can be transmitted through meiosis to offspring, resulting in the mutation being present in every cell of the progeny.

Somatic Mutation

A non-heritable mutation occurring in non-reproductive cells post-fertilization that is transmitted exclusively to clonal descendants via mitosis, producing a localized mutant cell population.

Mosaicism

A genetic condition characterized by the coexistence of two or more genetically distinct populations of cells within an individual, arising from post-fertilization somatic mutations.

Transition Mutation

A point mutation (base-pair substitution) in which a nucleotide base is replaced by another base within the same structural class—either a purine to purine ($A \leftrightarrow G$) or a pyrimidine to pyrimidine ($C \leftrightarrow T$).

Transversion Mutation

A point mutation (base-pair substitution) in which a nucleotide base is replaced by a base from a different structural class, such as a purine replaced by a pyrimidine or a pyrimidine replaced by a purine ($A \leftrightarrow C$, $A \leftrightarrow T$, $G \leftrightarrow C$, or $G \leftrightarrow T$).

Missense Mutation (Nonsynonymous)

A point substitution mutation within a protein-coding sequence that alters a codon to specify a different amino acid during translation (e.g., $\text{Leu (UUA)} \rightarrow \text{Ser (UCA)}$), which can be beneficial, neutral, or detrimental.

Silent Mutation (Synonymous)

A point substitution mutation within a coding sequence that alters a single nucleotide base without altering the resulting amino acid sequence due to genetic code redundancy (e.g., $\text{Ser (UCA)} \rightarrow \text{Ser (UCG)}$).

Nonsense Mutation

A point substitution mutation within a protein-coding sequence that converts an amino acid codon into a premature stop codon (e.g., $\text{Ser (UCA)} \rightarrow \text{STOP (UAA)}$), causing premature termination of translation.

Indel Mutation

A mutation characterized by the insertion or deletion of one or more nucleotide bases within a DNA sequence, frequently causing a frameshift unless the alteration occurs in precise multiples of three base pairs.

Suppressor Mutation

A secondary mutation occurring at a separate site from an initial mutation that compensates for, hides, or reverses the phenotypic consequence of the primary mutation.

Back Mutation (Reverse Mutation)

A mutation that directly restores an altered nucleotide back to its exact wild-type sequence.

Strand Slippage

A spontaneous replication error wherein DNA polymerase temporarily dissociates at repetitive nucleotide sequences, permitting template and nascent strands to misalign into loops upon reassociation, leading to nucleotide insertions or repeat expansions.

Deamination

A spontaneous or chemically induced mutagenic reaction involving the loss of an amino group ($-\text{NH}_2$) from a nucleotide base—such as the conversion of cytosine to uracil—which leads to base mismatching biased toward $G:C \rightarrow A:T$ transitions.