exam 2: gene function: dissection thru mutation Flashcards
definition of genes
specific region on a chromosome that may or may not code for protein
how do genes affect phenotype? Why do some alleles produce 1 phenotype and other alleles produce another phenotype
mutations
definition of mutation
heritable changes in base sequences that modify info content of DNA
a forward mutation
`wild (common>1&%)—>mutant
reverse mutation (reversion)
mutant —-> wild
types of mutations
-substitution
-deletion
-insertion
-inversion
-reciprocal translocation
mutation: substitution
change identity of specific base
types:
1. transition:
purine to purine (A/G)
pyrimidine to pyrimidine (C/T)
- transversion:
purine to pyrimidine
pyrimidine to purine
which is more likely to happen?
transition bc substituting a chemiclaly similar structure to another is an easier process
mutation: deletion/ insertion
deletion: one or more base lost in dna
insertion: one or more bases added to DNA
mutation: inversion
one piece of DNA rotates 180 in chromosome
-if large enough piece, may involve >1 gene
GATGTGA
AGTGTAG
mutation:reciprocal translocation
pieces of 2 nonhomologous chromosome change places
mutation rate (how often)
approx. 1 in 10000- 1 in 1000000 gametes carry a mutated allele
-> 1 mutation in 30000 (0.03-3 gametes)
rate: forward mutations usually occur more often than reversions. Why?
- way more ways to do that (convert wild-> mutant)
- more wild type alleles in a pop. than a mutant allele in a pop.
what causes mutation
-spontaneous
-in response to smth
spontaneous mutation
-some are completely random
-mutation occurs but does not become transparent until environment changes
ex. antibiotic resistance?
question regarding antibiotic resistance
due to spontaneous: should expect only a few random individuals to have resistant genotype
due to exposure of antibiotic: should expect to see resistance develop in an equal # of individuals exposed to the same antibiotic
Antibiotic resistance experiment (luria and Delbruck)
if spontaneous: only some plates would have resistance bacteria AND they would appeatin diff, random #
if result of exposure: all plates would have abt the same # of resistant bacteria
RESULT: spontaneous mutation
why do resistant bacteria only become pervasive when in presence of antibiotic?
new selection pressure only resistant bacteria can survive
spontaneous mutation: depurination
hydrolysis of A or G from sugar phosphate backbone ; no base (lose A/G)
Spontaneous mutation: replication error
DNA polymerase incorporates wrong base during replication
-very rare: 1 base in 109 mutates bc of this error
why so rare: reciprocal translocation(nonhomolog)
spontaneous mutation:deamination
loss of amino from base; particularly bad if lost from C changes to U
what controls protein repair enzyme?
genes
spontaneous mutation: unequal exchange of homologous chromosomes
(recombination between homologous)
will duplicate some genes on 1 homologue and delete those genes from the other homologue
=-~
=-~
—->
=–~
=~
spontaneous mutation: transposable elements
Transposable elements (TE): several hundred to several thousand nucleotides that move from 1 place to another in genome; may interupt gene (copy and move 1 genome to another)
Info on Transposable elements (TE)
-can cause serious mutation if TE moves inside exon of a gene
-5% of human genome composed of TEs called Alu elements
-300 bp long Alu elements is able to copy and insert themselves anywhere in genome (random)
homozygous: no insert
heterozygous: insert
spontaneous mutation: trinucleotide repeats
tandem repeats of specific amino acid codon can change in # ( 3 bases that get repeated over and over )
why do trinucleotide repeat mutation matter
-tandem repeats of specific aa codon can mutate in # of repeats
-few can lead to thousands
how would change in repeat # affect polypeptide?
changes the folding-> r-groups–> change function
examples:
1. fragile X syndrome
2. huntington’s disease
fragile X
gene involved in the formation of neural synapses (multiple CGG repeats )
5-54 repeats develop normal synapses
200-400: fragile X syndrome
50-200 may show signs but have high risk have producing gametes 200-400 repeats
==>premutation alleles: mutatuon occurs during gametogenesis
*the higher the repeats, the greater the risk of producing gamates w even more repeats (expressivity)
*severity of disease replated to repeat # (more repeats, more severe redardation) - intensity
much greater in women
huntington
huntingtin-34 repeats
42 or more: have disease ( kill neuron)
35-41: premutation alleles (expansion mutation) -risk of mutation highest in man
nonspontaneous mutation: mutagen
chemical/ physical agent that raise frquency of mutations above spontaneous rate
ways mutagens occur
- X-rays: break sugar phosphate backbone; when pieces ligated back tgt, they ligate the bases but the bases may in inverted/ deleted (DNA make extra copies of that)
- UB radiation: form dimers between adjacent bases
-during translation (T-T)
-T attached to backbone should not be stuck tgt, should be space
-when expose, cause the dimers to alter and fuse tgt
DNA repair mechanism
many enzymes work to repair mutation
ex. photolyse breaks uv-induced dimers
some remove damage DNA and replace w undamaged DNA
DNA repair: base excision
-single base
repair enzymes remove a damanged base and remove it
dna repair: nucleotide excision
multiple bases
enzymes that remove several bases surrounding damaged DNA and replace the
Dna repair: mismatch repair enzymes
rmoves and replace mismatch base (and some around it) incorrectly yout in by DNA polymerase
if theres too much damage, and DNA repair ezymes cant fix, then what
cells go thru apotosis (kill themselves to stop further mutation)
if apotosis fail?
cancer
if mutation oocur in genes controlling dna repair,?
cancer
CCR5 receptor mutation and HIV resistance
resistance ppl have deletion part of the CCR5 receptor makes a non fucntional receptor
(a piece of the receptor that virus use to enter cell is missing, therefore they cant enter)
-must be homo for mutation to be resistance
-heter have intermediate resistance (half fucntional half not)
=an good ex of a random mutation that doesnt become apparant until the envuronment changes and provides selective advantage for the mutant allele
