Week 4 Flashcards
Mutation
All genome sequence variations are changes in sequence and therefore mutations
only a small proportion result in a change of phenotype
Four classes of genome sequence variations
Substitution
Indels
Inversion
Translocation
Substitution
Base subsituitions result in single nucleotide polymorphism (SNPs)
a base substitution results in a new allele
transition and transversion
Transition
Purine to purine
pyrimidine to a pyrimidine
Transversion
purine for a pyrimidine
pyrimidine for a purine
Transversion vs transition
for everyone transition there should be two traversions
transversions based on randomness should occur more frequently
but transitions occur more frequently
Indels
insertion and deletions
smallest: insertion and deletion of one base
define the break point at either end of the insertion
Deletions can remove a whole gene, insertions can be very large transposons.
Inversion
smallest inversion of two bases
look for breakpoints
Can be Mb in length.
Translocation
Movement of DNA between different chromosomes
look for breakdown
Mutation Rate
mutations over some measure of time
rate is concerning a measure of time, generation, cell, division
Two mutation rates
Gene mutation rate
Mutation rate = genome variation rate
Two mutation rates
Gene mutation rate
Mutation rate = genome variation rate
Gene mutation rate
mutation disrupts allele causing a detectable change in the phenotype
Bacterial gene rate: 2-8 10^-9/division
Drosophila gene: 5-50 x 10^-6/gamete
Human gene rate 1-30 x 10^-6/gamete
Gene mutation rate varies from gene to gene. Some genes are larger providing more location for a mutation to take place
Mutation Rate
Mutations over some measure time
Bacterial rate 1-10 X 10-10/ bp division
Eukaryotic rate 1 X 10-8/ bp gamete
Somatic rate 3 X 10-9/ bp mitosis
COVID 19 rate 8 X 10-4 / bp year (25 / year)
Consequence of Mutation Rate
1-Evolutionary change
2-Animal cloning
Mutations and evolutionary change
generation after generation genomes change
Clones of cells with somatic mutation. Different mutations occurring in different cells.
Ratio of transitions to transversions.
Predicted: 2 transversion for every transition
Observed: 2 transition for evert tranversion
changes in genome sequences are caused by mechanism
in coding DNA it is 3 transition for every transversions
Spontaneous Replications errors
Tautomeric shifts
Wobble
Strand Slippage
Unequal crossing over
Tautomeric shift
Aromatic rings can be tautomers not just one structure
protons can move between the nitrogen and oxygen
results in alternate base pairing; can result in replication errors,
A-C
T-G
Wobble
tRNA binding in codons
but we can get it in DNA
Thymine guanine wobble in which they line up slightly differently and in that different conformation hydrogen bonds are beginning to form
alternative base pairing mechanisms
T-G
A-C
Strand Slippage
Indels
during DNA replication when you replicate through areas of low complexity DNA polymerase can sometimes when its pulling strands apart and trying to synthesize DNA place this A down on the T casuing the loop out on the A. Insertion of an A to strand slipagge on the newly sequenced strand.
slippage of the template strand, deletion.
slippage of the newly synthesized strand, insertion
Unequal crossing over
Improper alignement of repeats
Spontaneous Chemical Changes
Deamination
Depurination
Deamination
Due to the instability of amine on cytosine
cytosine has a rate of deamination
deamination results in uracil
5-methylcytosine to thymine
results in a transition mutation
Depurination
Purines can spontaneously leave DNA
Apurinic site: sugar phosphate but no base
Mutagens
1-Base analogs 2-Alkylating Agents 3-Deaminating chemicals 4-Hydroxylamine 5-Oxidative radicals 6-Intercalating agents 7-UV light
