Gene and Chromosomal Mutations Flashcards
what are the two types of cells in which mutations can occur, and what are their effects on successive generations?
germline: in reproductive cells (eg. germ cells and gametes), may be transmitted to offspring and to successive generations
somatic: non-reproductive, not inherited by progeny
what are gene/point mutations, and the two basic types of changes?
they involve chemical changes that affect the DNA sequence of just (one or a few bases in) a single gene
two basic types of changes:
1. nucleotide substitutions
2. nucleotide insertions or deletions
what is nucleotide substitution, and what four mutations can nucleotide substitutions result in?
nucleotide substitution: the replacement of one nucleotide pair with another
possible mutations: missense, nonsense, silent, neutral
what are nucleotide insertions or deletions, and what two types of insertions or deletions can occur?
nucleotide insertions or deletions: additions or losses, respectively, of one or more nucleotide pairs in a gene
- addition or deletion of deoxynucleotides in multiples of 3 (codons): missense or nonsense
-addition or deletion of deoxynucleotides not in multiples of 3: frameshift mutation –> extensive missense or nonsense
often has deleterious effects, since resulting mRNA is continuous and read as a series of non-overlapping codons (three nucleotides each)
what is a missense mutation, and how can it be caused?
- one mRNA codon changes
- one different amino acid translated
- specific 3D conformation of protein changed, function altered
caused by: nucleotide substitution or nucleotide addition or deletion (in multiples of 3)
what is a nonsense mutation, and how can it be caused?
- one amino acid codon changed into stop codon (UAA UGA UAG)
- premature termination of translation
shorter, truncated polypeptide - amino acid sequence shortened, specific 3D conformation of protein changed
- function of protein altered
- most nonsense mutations produce non-functional proteins
caused by: nucleotide substitution or nucleotide addition (of stop codon)
what is a silent mutation, and how can it be caused?
- one mRNA codon changed
- same amino acid translated due to degeneracy of genetic code (multiple codons code for one amino acid)
- no change in specific 3D-conformation of protein
- function of protein unaltered
caused by: nucleotide substitution only
what is a neutral mutation, and how can it be caused?
- one mRNA codon changed
- one different amino acid translated
- resulting amino acid produces no detectable change in the function of the protein translated
two reasons:
1. original aa substituted with aa of similar physical and chemical proteperties
2. aa substituted is non-essential to protein’s structure and function
caused by: nucleotide substitutions
what is a frameshift mutation, and how can it be caused?
- produces different amino acid subsequent to site of mutation
- may result in extensive missense or nonsense mutations
- protein produced is severely altered (specific 3D conformation changes / protein truncated), either change in / non-function protein
caused by: nucleotide addition or deletion, not in multiples of three
what mutation causes sickle-cell anemia, and how does this occur?
substitution mutation leads to missense mutation in beta-globin gene (which encodes one of the polypeptide subunits that make up haemoglobin, Hb)
substitution of a thymine for an adenine at one position in Hb gene (template, non-coding strand): missense mutation
6th aa residue in plp changed from glutamate (hydrophilic) to valine (hydrophobic)
specific 3D conformation and function of Hb protein altered
hydrophobic spot outside protein sticks to hydrophobic region of an adjacent Hb protein’s beta chain
why are red blood cells sickle-shaped in sickle-cell anemia, and what are the physiological effects of this?
(glutamic acid to valine) mutant Hb subunits tend to stick to one another when O2 concentration is low
forms fibre-like structures within red blood cells
(at high O2 concentration, Hb resumes globular structure)
red blood cells lose normal morphology, become sickle-shaped
sickled cells less able to move through capillaries and block blood flow
severe pain and cell death due to oxygen shortage
cells are fragile and easily destroyed, decreasing oxygen-carrying capacity of blood
what is the production of mutations called, and what are the two types of ways it can occur?
- mutagenesis
spontaneous: occur naturally, without use of chemical or physical mutagenic agents; result of errors during DNA replication, recombination, or repair
induced: due to deliberate application of mutagens (chemical or physical agents) that result in increased mutation rates
how do mutations occur during DNA replication and repair?
- DNA replicates with fairly high fidelity, but DNA polymerase may insert the wrong nucleotide / too many / too few nucleotides; mistakes at the rate of 1 in every 100,000 nucleotides (6 billion base pairs in each diploid human cell, 120,000 mistakes every time a cell divides)
- proofreading: DNA polymerase enzymes recognise mistakes, replace incorrect nucleotide during DNA replication OR mismatch repair: enzymes recognise and fix deformities in secondary structure of DNA by removing and replacing
some replication errors fail to be recognised by repair enzymes
how do mutations occur during DNA slippage?
- during DNA replication, strand folds back
- mispairing between daughter DNA strand and parental template strand
- parts of DNA copied more than once (if duplicated segment is a gene, gene duplication occurs)
what are the two physical agents that act as mutagens, and what are their effects on DNA?
physical agents act by exposing DNA to more radiation
- X-rays
results in production of free radicals of water (OH radical), very reactive
interact with DNA to produce double-stranded breaks, leading to chromosomal rearrangements and deletions - UV rays
absorbed by bases of DNA
production of covalent attachment between adjacent pyrimidines in one strand (thymine dimers)
OR
base pair substitutions, insertions and deletions
*DNA replication and transcription are blocked, lethal if unrepaired
