Chapter 18 Lecture 12 Flashcards
The Tinman gene
aka NKX2.5
studies in flies in 1980s
- mutations in a gene prevented heart development
- fail to form the muscle of the midgut and heart
Somatic mutations
arise in tissues other than those that produce gametes
- impact is restricted to the individual
- not in germline so won’t be passed
germ-line mutations
arise in tissues that produce gamets
- can be passed to offspring
Are gene mutations always harmful?
no, source of all genetic variation
source of organisms ability to adapt to environment
De novo mutation
an alteration in a gene that is present for the first time in one family member as a result of a mutation in a germ cell (egg or sperm) of one of the parents or in the fertilized egg itself
- can be germ-line or somatic
- NOT INHERITED FROM PREVIOUS GENERATIONS
Frame shift mutations: insertion and deletions
addition or removal of one or more nucleotide pairs
- changes the reading frame
common way of inactivating a protein
in-frame deletion
deletion or insertion of a multiple of 3 nucleotides that does not alter the reading frame
expanding nucleotide repeats
repeated sequence of a set of nucleotides in which the number of copies of the sequence increases
missense mutation
base substitution that results in a different amino acid
nonsense mutation
mutation that changes a sense codon into a termination codon
forward muation
mutation that alters the wild-type phenotype
backward mutation
mutation that changes the mutant phenotype back into the wild-type
silent mutation
mutation changes the codon sequence but not the amino acid
neutral mutation
missense mutation that alters the amino acid sequence but does not change the function of the protein
loss of function mutation
causes the complete or partial absence of a normal protein function
- usually recessive
lethal mutation
causes premature death
is a nucleotide change does not change the amino acid, doe it have no effect?
not always; can have phenotypic changes
- could change the rate of protein synthesis
- also can change if mRNA translated or not
gain of function mutation
produces an entirely new trait or causes it to appear in an inappropriate tissue or at an inappropriate time
suppressor mutation
genetic change that hides or suppresses the effect of another mutation
- intragenic- same gene of mutation
- intergenic - in another gene
How is a suppressor mutation different from a reverse mutation?
reverse restores original phenotype by returning to wild-type and a suppressor restores the phenotype by causing an addition change in the DNA at a site different than mutation
gain or loss of a nucleotide in the coding sequence is very likely to be devastating to protein function. why?
alters the reading frame and may change many codons
expanding nucleotide repeats
mutations in which the number of opies of a set of nucleotides increases
- ex. fragile x and huntingtons
- number of repeats often leads to severity of disease
what 3 factors affect mutation rates?
- freq with which the changes arise in DNA
- how often changes are repaired by DNA-repair mechanisms
- ability to detect a mutation
tautomeric shifts
proton position shifts, allowing mispairing
Indels
small insertion or deletions that result from unequal crossing over
strand slippage
newly synthesized strand forms a loop
can result in insertion or deletion
depurination
loss of a purine
- result NT can’t pais
- cause presence of endogenous metabiline undergoing chemical reactions
deamination
loss of an amino groups
- can result from nitrous acid
- corrected by enzyme thymine-DNA glycolase
intercalating agents
proflavin, acridine orange, ethidium bromide
- disrupt rotation of pairing and assumes carcinogenic
Base analogs are mutagenic because of which characteristic
a. they produce changes in DNA polymerase that cause it to malfunction
b. the distort the structure of DNA
c. they are similar in structure to the normal bases
d. they chemically modify the normal bases
c. they are similar in structure to the normal bases
base analogs are incorportated into DNA and frequently pair with the wrong base thus altering their pairing properties
ionizing radiation
dislodges electrons n tissue causing free radicals which often damages DNA
UV light induces the formation of pyrimidine dimer
two thymine bases that block replication
sos system in bacteria
sos system allows bacteria cells to bypass the replication block with a mutation-prone pathway
spontaneous mutation vs induced mutation
spontaneous occur under normal condition and happen naturally
- induced cause by environmental chemicals or radiation
explain how some types of induces mutation occir, such as the effects of base analogs, intercalating agents, oxidative reactions, and UV light
base analogs are incorportated into DNA and frequently pair with the wrong base thus altering their pairing properties
- intercalating agents - wedge between the bases and cause single-base insertions and deletions in replication
- oxidative - change the structure of DNA bases
- UV light induces the formation of pyrimidine dimer two thymine bases that block replication
what kind of mutations are most often created by UV radiation
formation of pyrimidine dimers that disrupt replication and transcription
Mismatch repair
corrects incorrectly inserted nucleotides that escape proofreading
- enzymes cut out a section of the newly synthesized strand and replace with new NTs
direct repair
change altered nucleotides back into their correct structures
base-excision repair
glycosylase enzymes recognize and remove specific types of modified bases; entire NT removed and a section of the polynucleotide strand is replaces
nucleotide-excision repair
removes and replaces many types of damaged DNA that distort the structure. two strands separated, a section containing distortion removed, DNA polymerase fills in the gap and DNA ligase seals the filled in gap
how do direct-repair mechanisms differ from mismatch repair and base-excision repair?
direct return an altered base to its correct structure without removing and replaces NT
the other removes and replace NTs
double strand repair breaks
homologous recombination
or
nonhomologous end joining
transposons
mobile DNA sequences found the the genome
- most able to reinsert at many different locations
- often cause mutations
common features of ransposons
short flanking repeats (3-12 bp) on both sides
-no not travel with
-regenerated at pt of insertion
staggered cuts in target DNA, leaving short, single stranded pieces on either side of transposable element
- replication of ssDNA create flanking direct repeats
- terminal inverted repeats at ends of many elements
mechanism of transposition
- staggered breaks made in target DNA
- transposable element is joined to single stranded ends of target DNA
- dNA is replicated at the single-strand gaps
replicative transposition
“copy and paste”
- copy made, jumps to new, leave old there
- increases # of copies of element
- can be between two different DNA molecules or between 2 parts of the same DNA molecule
nonreplicative transposition
“cut and paste”
- excised from old and inserted to new
- no increase in copies
- cleavage require transposable enzyme
- joining carried out by normal replication and repair enzymes
- old site typically repairs using homologous sister chromatid
retrotransposons
elements that transpose through RNA intermetiate
RNA transcribes, copied back to another DNA site using reverse transcriptase,
- only through replicative transposition
- more common thanDNA transposons in eukaryotes
how are flanking direct repeats created in transposition?
staggered cuts are made in DNA and the transposable element inserts into the cut. later replication of the single-stranded pices of DNA creates short flanking direct repeats on either side of the inserted transposable element
briefly explain how transposition causes mutationand chromosome rearrangements
becaus it inserts into a gene, destroying its function,
-chromosome rearrangements arise becuase transposition includes the breaking and exchange of DNA sequences.
additionally multiple copies of a transposable element may undergo homologous recombination, producing chromosome rearrangements
which type of transposable element possesses terminal inverted repeats?
a. insertion sequence
b. composite transposons
c. noncomposite transposon Tn3
d. all the above
d. all the above
what are the two groups of eukaryotic transposons
- structurally similar to transposable elements in bacteria
- -typically end in short inverted repeats
- -transpose DNA
- maize and fly
- retrotransposons
- -similar to retroviruses
- -include alu elements in humans, Ty in yeast, Copia in flies
SINES
short interspersed nuclear elements
-11% of genome
include Alu
LINES
long interspersed nuclear elements
-approx 9000,000 copes in human genome
-most can’t jump
21% of total human genome
Barbara McClintock
40/50s discovered transposition in maize
- 1983 nobel prize
- only women to receive unshared prize
- showed genes are responsible for turning physical characteristics on and off
first known active human transposon
L1 element
- causing a de novo case of hemophilia
- result of retrotransposition into the factor VIII gene
