Topic 6 Flashcards
(44 cards)
Mutations in which organ has the greatest evolutionary effect?
the gonads
What are the two types of mutations?
Germinal: only mutations in the germ cells will be transmitted to the progeny
Somatic mutations: will impact the individual where the mutation occurs but are evolutionarily irrelevant
What is the reigning paradigm of mutations?
Mutations can occur in any cell at any time, and their occurrence is ‘random’.
True or false? Mutagenic processes are at a constant tug-of-war with eachother.
True
DNA is a remarkably stable molecule, but it can still be damaged due to chemical or physical stress on the double helix.
What are the five types of damage?
(1) Abasic sites (loss of nucleotide, not backbone)
(2) Base mismatches
(3) Modified bases
(4) Inter- and intra-strand crosslinks
(5) Double stranded breaks (DSBs)
What is the range of genetic mutations?
Causes everything from point mutation (1bp affected) to structural changes affecting the whole chromosomes (deletions, inversions, duplications, translocations)
Compare spontaneous and induced mutations.
spontaneous mutations are mostly from replication errors (polymerase-induced mistakes) followed by defects in the DNA repair mechanism. The rate of spontaneous mutations is very low and varies according to gene size, domains on the chromosome, genome characteristics, and cell age.
Induced mutations (known as chemical and physical agents or mutagens) have a higher frequency and include base analogs, hydroxylating agents, alkylating agents, deaminating agents, intercalating agents, UV radiation, and ionizing radiation.
What are point mutations and where do they take place?
Single base pair changes or single nucleotide polymorphism (SNP) that can occur anywhere in the genome (coding regions, intergenic regions, non-coding regions of genes like promoters, UTRs, or introns)
What are the three types of point mutations?
(1) Base substitutions
(2) Base deletion
(3) Base insertion
What are the kinds of base substitution point mutations?
Transition:
purine replaced by a purine (A-G, G-A)
pyrimidine replaced by a pyrimidine (C-T, T-C)
Transversion:
purine replaced by a pyrimidine (A-C, A-T, G-C, G-T)
Pyrimidine replaced by a purine (C-A, C-G, T-A, T-G)
Name synonymous and non-synonymous mutations.
Synonymous:
Silent mutations- encodes the same amino acid, usually in the third degenerate position, with no effect on the phenotype
Non-synonymous:
Missense Mutations- codes for a different amino acid
Nonsense mutations- changes to a STOP codon, likely severe
What will cause for a missense mutation to either retain protein function or not?
Chemically similar– conservative, may retain protein function
Chemically different– non-conservative, more likely to affect protein function
Describe a frameshift mutation.
Removal or addition of base pairs disrupts the triplet reading frame.
The result is the translation of an abnormal series of aa downstream from the indel and the increased chances of a premature STOP codon producing a truncated protein.
Indels (insertions/deletions) that are multiple of three reconstitute the frame downstream of the last mutation site
Explain functional consequences of mutations in the non-coding regions of DNA.
Point mutations in regulatory regions required for gene expression (promoters, enhancers, etc.) or that are involved in mRNA processing and stability (splice sites, UTRs) may ultimately affect how much protein is made
A mutation in the Shine-Delgarno sequence will effect
(a) Prokaryotic transcription
(b) Eukaryotic transcription
(c) Prokaryotic translation
(d) Eukaryotic translation
(e) none of the above
Prokaryotic translation
This ribosomal binding site in bacterial messenger RNA became known as the Shine-Dalgarno (SD) sequence enables initiation of protein synthesis by aligning the ribosome with the start codon.
What mutation is caused by error in replication?
DNA slippage causes indels during replication– usually of repeated regions
What does slippage mutations result in?
The daughter strand gets looped and that part of the template is repeated
What is the result of CGG expansion in Fragile X syndrome?
The methylation of 5’ regulatory sequences and transcription silencing
Note: slippage is behind an important class of mutations defined by trinucleotide repeats that explains over 40 inherited neurological diseases such as Fragile X syndrome (CGG repeats in the FMR1 gene) and Huntington Disease (CAG repeats in the huntington gene)
How does energetically favourable hydrogen bonding ensure DNA strand complementarity? How do nucleotide mispairing mutations occur?
The geometric correspondence between purine and pyrimidines allows the specific formation of weak hydrogen bonds. Unfavourable associations are prevented because hydrogen atoms are either too far away or repulsed by close proximity.
Alteration of the chemical geometry (isomerization) of nucleotides can change the favourable hydrogens suitable for pairing, and break complementarity rules.
Mismatches in the replicating DNA strand is correct by…
DNA polymerase proofreading (5’ to 3’ exonuclease activity and by DNA repair mechanisms)
Describe the three cellular environmental mutation causes: depurination, deamination, and oxidative damage
Depurination: loss of purine base (G or A), efficiently repaired by endogenous DNA repair mechanisms
Deamination: removal of an amine (-NH2) group from C, A and G, alters base pairing (with the exception of Xanthine) and leads to mutations during replication
Oxidative damage: reactive Oxygen species (ROS) are byproducts of aerobic metabolism in mitochondria induced by ionizing radiation. ROS agents can damage DNA in several different ways, leading to replication stall or mismatch pairings
Define mutagen
a chemical or physical force that can increase the mutation rare above mu (p)
What are three functions of mutagens?
Mutagens can:
(1) replace a base pair in the DNA strand
(2) chemically alter a base pair leading to a mismatch
(3) damage a base pair such that it cannot base pair with any other nucleotide
Give some examples of chemical and physical types of mutagen agents.
Chemical agents:
alkylating agents, ROS, intercalating agents, DNA adducts, base analogs
Physical agents:
UV/ionizing radiation
