Unit 18- mutations Flashcards
mutations
inherited alterations in the DNA seq
- source of genetic variation
- source of many diseases and disorders
adaptive mutation
- genetic variation critical for evolutionary change that brings about adaptation to new environments
- stressful conditions, where adaptation might be necessary to survive, induce increased mutation in bacteria
causes of mutations
- spontaneous replication error
- spontaneous chem changes
- chemically induced mutations
- radiation
Big categories of mutations
- somatic mutations (all cells derived from that cell with have the mutation)(mitosis)
- germ-line mutations (offspring that came from mutant cell will be completely mutated)(meiosis)
base substitution: transition
the substitution of a purine for a purine or of a pyrimidine for a pyrimidine
base substitution: transversion
substitution of a pyrimidine for a purine or of a purine for a pyrimidine
insertions and deletions: frameshift
affects the reading frame
insertions and deletions: in-frame
does not affect the reading frame
expanding nucleotide repeats
increase the number of copies of a set of nucleotides (fragile sites)(hairpins. 2/3 bases pairing)
forward mutation
wild type —> mutant type
reverse mutation
mutant type —> wild type
missense mutation
amino acid —> diff amino acid
nonsense mutation
sense codon —> stop codon
synonymous mutation
change the base but don’t change amino acid
silent mutation
codon —> synonymous codon (no change in AA seq!)
neutral mutation
no change in function
phenotypic effects of mutations
- loss-of-function mutation
- Gain-of-function mutation
- Lethal mutation
Suppressor mutation
a mutation that hides or suppresses the effect of another mutation
- Intragenic (second mutation at diff site in SAME GENE hides mutation in another site)
- Intergenic (mutation in second gene that hides mutation in first gene)
Factors Affecting Mutation Rates
- Frequency of a change in DNA
- probability that when a change takes place, that it will be repaired
- probability that a mutation will be detected
strand slippage
strand loops out when pairing lots of identical pairs, creating an additional nucleotide if new strand or removal of a nucleotide if template strand
unequal crossing over
causes crossing over and deletions in the same event
radiation
greatly increases mutation rates in all organisms
thymine dimer
two thymine bases dimerized (covalently bonded) and block replication
SOS system in bacteria
allows bacterial cells to bypass the replication block with a mutation prone pathway
Ames Test
used to identify chem mutagens
- place mutant bacteria in min medium = no bacteria (control)
- mutant bacteria mixed with chem for mutagenic activity. Placed on min medium = lots of bacteria (his- mutant —> his+ wild type)
The chem was mutagenic as it changed the bacteria
repair pathways
- mismatch repair
- direct repair
- base-excision repair
- nucleotide-excision repair
mismatch repair
- Mismatched bases and other DNA lesions are corrected by mismatch repair.
- Enzymes cut out a section of the newly synthesized strand of DNA and replace it with new nucleotides.
direct repair
restores the correct structures of altered nucleotides
base-excision repair
glycosylase enzymes recognize and remove specific type of modified BASE. Then ENTIRE NUCLEOTIDE is removed, and a section of the polynucleotide strand is replaced.
*nucleotide-excision repair
- removes and replaces damaged DNA that distorts the DNA structure
- 2 strands of DNA are separated, a section of the DNA containing the distortion is removed, DNA polymerase fills in the gap, and DNA ligase seals the filled-in gap.
repair of double-strand breaks
- homologous directed repair: if homology is available (ex: sister chromatids)
- nonhomologous end joining: joins any broken ends together, error prone
translesion DNA polymerases
allow replication to proceed past bulky distortion in DNA but error prone
Transposable elements
sequences that can move about the genome
Transposition: movement of the transposons
Flanking direct repeats
generated when a transposable element inserts into DNA
(staircase cut with transposable ele in middle then flanking fills in both side top and bottom)
- both move right
terminal inverted repeats
inserted bases around transposable ele that face outward from ele
what can transposition take place through?
DNA or RNA intermediate
Replicative transposition (copy-paste
- AKA “retrotransposons”
- A new copy of the transposable element inserts in a new location, and the old copy stays behind.
- Requires reverse transcription to integrate into the target site
Nonreplicative transposition (cut and paste)
- AKA “DNA transposons”
- The old copy excises from the old site and moves to a new site.
Control of transposition
Many organisms limit transposition by methylating the DNA in regions where transposons are common.
Transposition in humans
About 45% of the human genome comprises sequences that are related to transposable elements, mostly retrotransposons.
Transposons cause mutations by
- Inserting into another gene
- Promoting DNA rearrangements
Examples
- Approximately half of spontaneous mutations in Drosophila
- Human genetic diseases
- The color of grapes
Bacteria: Insertion sequences
Carries only the genetic information needed for transposition
Bacteria: Composite transposons
Flanked by two copies of an insertion sequence that may itself transpose
Bacteria: Noncomposite transposons
- Lack insertion sequences
- Possess a gene for transposase and have terminal inverted repeats
Eukaryotic: sim transposons to bacteria
Short inverted repeats
- P elements in Drosophila
- Ac and Ds elements
Eukaryotes: Retrotransposons
- Ty elements in yeast
- Copia elements in Drosophila
- Alu sequences in humans
