Gene Mutation, DNA Repair, and Transposition

Vocabulary practice flashcards covering types of gene mutations, phenotypic impacts, mutagens, spontaneous DNA alteration mechanisms, DNA repair pathways, and transposable elements based on Chapter 15.

Mutation

An alteration in the nucleotide sequence of an organism's genome.

Point Mutation

A genetic change that alters the identity of one or a few base pairs, or adds/deletes a few base pairs, segregating as a single genetic point.

Somatic Mutation

A mutation occurring in non-germline cells during mitotic DNA replication, affecting only the descendants of that cell in the individual and potentially leading to somatic mosaicism (such as in Proteus syndrome).

Germ-Line Mutation

A mutation occurring in gametes that is transmitted to offspring, resulting in all cells of the new individual carrying the mutation.

Loss-of-Function Mutation

A mutation that causes a gene not to be expressed or produces a nonfunctional protein; it is almost always inherited in a recessive manner.

Gain-of-Function Mutation

A mutation that produces an altered gene product with novel or enhanced properties, typically exhibiting dominant inheritance.

Haploinsufficiency

A condition in which one functional allele is inactivated by mutation and the single remaining functional wild-type allele produces insufficient protein product to maintain a normal phenotype (e.g., Marfan syndrome due to reduced fibrillin from the FBN1 gene).

Dominant Negative Mutation

A dominant mutation in which the altered, defective gene product actively interferes with the function of the normal wild-type gene product.

Transition

A point mutation substitution where a purine is replaced by another purine ($A \rightarrow G$ or $G \rightarrow A$) or a pyrimidine is replaced by another pyrimidine ($C \rightarrow T$ or $T \rightarrow C$).

Transversion

A point mutation substitution where a purine is replaced by a pyrimidine, or a pyrimidine is replaced by a purine.

Silent Mutation

A nucleotide substitution within a coding region that changes a codon to a synonymous codon without altering the specified amino acid, due to the degeneracy of the genetic code.

Missense Mutation

A nucleotide substitution that alters a codon to specify a different amino acid; classified as conservative if the replacement amino acid shares similar side-chain properties, or nonconservative if its side chain is chemically distinct.

Nonsense Mutation

A base substitution within a protein-coding sequence that converts an amino acid-specifying codon into a premature stop codon, terminating translation and truncating the polypeptide.

Nonstop Mutation

A base substitution that converts a normal termination (stop) codon into an amino acid-specifying codon, resulting in an abnormally lengthened polypeptide chain.

Frameshift Mutation

An insertion or deletion of one or two base pairs (or any number not a multiple of $3$) in an open reading frame that shifts the downstream triplet reading frame, changing all subsequent amino acids.

Luria-Delbrück Fluctuation Test

A $1943$ fluctuation experiment using Escherichia coli and T1 bacteriophage demonstrating that mutations arise randomly and spontaneously prior to exposure to a selective agent, rather than as an adaptive response to environmental stress.

Tautomeric Shift

A reversible chemical isomerization of a nitrogenous base via a single proton shift (such as keto-enol or amino-imino transitions) that alters hydrogen-bonding capabilities and causes transition mutations during DNA replication.

Replication Slippage

An error during DNA synthesis where DNA polymerase slips or a strand loops out, commonly occurring at short tandem repeats or palindromes and producing insertions or deletions.

Depurination

The spontaneous loss of a purine nitrogenous base (guanine or adenine) caused by hydrolysis of the glycosidic bond between the deoxyribose $1'$\text{-carbon} and the purine's $\text{N-9}$ atom, creating an apurinic (AP) site.

Deamination

The removal of an amino group from a nitrogenous base (e.g., converting cytosine to uracil or adenine to hypoxanthine), leading to altered hydrogen-bonding properties and base-pair transitions during replication.

Base Analog

A chemical mutagen structurally similar to a normal nitrogenous base that can substitute for it during DNA replication, predisposing the strand to anomalous base-pairing and transition mutations (e.g., 5-bromouracil, 2-aminopurine).

Alkylating Agent

A chemical agent that covalently donates an alkyl group (such as methyl or ethyl) to reactive positions on nucleotide base rings (e.g., ethylmethane sulfonate / EMS alkylating keto groups on position $6$ of G or position $4$ of T).

Intercalating Agent

A chemical mutagen possessing a flat, planar ring structure that slips and wedges between adjacent DNA base pairs, distorting the double helix and interfering with replication, repair, and transcription (e.g., ethidium bromide, doxorubicin).

DNA Adduct

A covalent complex formed between a bulky chemical compound and a nitrogenous base ring in DNA that interferes with replication and repair (e.g., acetaldehyde from cigarette smoke, heterocyclic amines from grilled meat).

Pyrimidine Dimer

A DNA lesion caused by ultraviolet (UV) radiation (optimally absorbed at $260\,nm$) in which covalent bonds form between adjacent pyrimidines (frequently thymines) on the same strand, distorting the double helix.

Trinucleotide Repeat Expansion

A form of mutation characterized by an increase in the number of unstable three-nucleotide tandem repeats during meiosis, associated with genetic diseases such as Huntington disease, Fragile X syndrome, and Myotonic dystrophy.

Anticipation

A genetic phenomenon in which the severity of a disease increases and the age of onset becomes earlier in successive generations due to the expansion of unstable triplet repeat sequences.

Mismatch Repair (MMR)

An S-phase repair system that detects and corrects base mismatches and small indels that escape proofreading; in bacteria, it utilizes DNA adenine methylase to discriminate between methylated parental strands and temporarily unmethylated new strands.

SOS Repair

An error-prone post-replication bypass mechanism activated as a last resort during extensive DNA damage, in which DNA polymerase inserts random nucleotides to allow replication past lesions at the expense of creating mutations.

Base Excision Repair (BER)

A multi-step repair pathway where a specific DNA glycosylase excises an incorrect base to form an AP site, followed by AP endonuclease cutting the backbone, DNA polymerase filling the gap, and DNA ligase sealing the nick.

Nucleotide Excision Repair (NER)

A light-independent repair mechanism in which multi-protein nuclease complexes (encoded by uvr genes in bacteria) recognize and excise an oligonucleotide fragment containing a bulky DNA lesion, followed by polymerase synthesis and ligation.

Xeroderma Pigmentosum (XP)

A rare autosomal recessive disorder caused by defective nucleotide excision repair (in genes XPA through XPG), causing extreme hypersensitivity to UV radiation and a $2000$\text{-fold} increased incidence of skin cancer.

Photoreactivation Repair

A light-dependent repair pathway in which photoreactivation enzyme (PRE / photolyase) absorbs visible blue light energy to directly cleave covalent bonds in thymine dimers and restore normal base pairing.

Homology-Directed Recombination Repair (HDR)

A high-fidelity double-strand break repair pathway occurring during S and $G_2$ phases that uses an undamaged complementary region of a sister chromatid as a template to synthesize across the damaged break.

Nonhomologous End Joining (NHEJ)

An error-prone double-strand break repair pathway operating when a sister chromatid is unavailable, in which specific proteins recognize broken ends, nucleases trim them to blunt ends, and DNA ligase rejoins them directly.

Ames Test

A bioassay that tests the mutagenic potential of chemical agents by measuring the reversion rate of histidine-auxotrophic ($\text{his}^-$) Salmonella typhimurium strains to wild type ($\text{his}^+$) in the presence of mammalian liver enzymes.

DNA Transposon

A Class $2$ transposable element that moves through a cut-and-paste mechanism without an RNA intermediate, flanked by inverted terminal repeats (ITRs) and typically encoding transposase.

Retrotransposon

A Class $1$ transposable element that transposes via a copy-and-paste mechanism using an RNA intermediate, requiring the action of reverse transcriptase and integrase.

Ac-Ds System

A maize transposable element system discovered by Barbara McClintock, wherein the autonomous Activator ($Ac$) element provides transposase activity that enables the nonautonomous Dissociation ($Ds$) element to transpose or cause chromosome breaks.

LINEs (Long Interspersed Elements)

Autonomous non-LTR retrotransposons ($1\text{--}6\,kb$ long, such as $L1$) that encode reverse transcriptase and integrase, comprising approximately $21\%$ of the human genome.

SINEs (Short Interspersed Elements)

Nonautonomous non-LTR retrotransposons ($100\text{--}500\,bp$ long, such as Alu elements) that lack protein-coding capacity, comprising approximately $13\%$ of the human genome and depending on LINE enzymatic machinery for retrotransposition.