Post on 01-Jan-2016
MutationsMutations
Can be a change Can be a change in the DNA base in the DNA base sequence or a sequence or a change in a change in a chromosomechromosome
Mutant- someone Mutant- someone who has a who has a mutationmutation
Consequences of Consequences of MutationsMutations Mutations can beMutations can be
– HelpfulHelpful Ex: Give immunity to HIVEx: Give immunity to HIV Ex: Give immunity to infectious diseasesEx: Give immunity to infectious diseases
– HarmlessHarmless– Harmful Harmful
Ex: Disease causing mutations (some Ex: Disease causing mutations (some have to be in homozygous form)have to be in homozygous form)
What do Mutations do?What do Mutations do?
Can stop or slow the production Can stop or slow the production of a proteinof a protein– Ex: Ex:
Cause a protein to overproduceCause a protein to overproduce– Ex:Ex:
Impair a protein’s functionImpair a protein’s function– Ex:Ex:
When can Mutations When can Mutations happen?happen? Germline mutation- happens before Germline mutation- happens before
meiosis; affects all cells in the new meiosis; affects all cells in the new organismorganism
Somatic mutation- happens before Somatic mutation- happens before mitosis; after only immediate daughter mitosis; after only immediate daughter cells and their descendents cells and their descendents – More severe the earlier it occursMore severe the earlier it occurs– Creates a mosaicCreates a mosaic– Can lead to some forms of cancerCan lead to some forms of cancer
Spontaneous Mutations Change occurs with no outside Change occurs with no outside
influenceinfluence
Often occurs because of a Often occurs because of a mismatch in base pairs during mismatch in base pairs during replicationreplication
Results in de novo mutationsResults in de novo mutations
Mutation RatesMutation Rates
Different in different genesDifferent in different genes Depends onDepends on
– Gene sizeGene size– Gene location Gene location – Gene sequenceGene sequence
Mutation Hot SpotsMutation Hot Spots
Sequence Regions Sequence Regions – That are repetitiveThat are repetitive– Symmetrical or Symmetrical or
repeated sequences repeated sequences on the same strandon the same strand
– Palindromes- Palindromes- sequence that reads sequence that reads the same forward the same forward and backwardand backward
Sections confuse Sections confuse replication enzymesreplication enzymes
Mutagen Mutagen
Substance causing Substance causing a mutationa mutation– ChemicalsChemicals– Radiation Radiation
Exposure can be Exposure can be accidental or accidental or purposeful purposeful
It can also come It can also come from the natural from the natural environmentenvironment
Types of MutationsTypes of Mutations
Point mutations- change of a single Point mutations- change of a single basebase– Transition- exchange of one pyrimidine for Transition- exchange of one pyrimidine for
another or one purine for anotheranother or one purine for another– Transversion- exhange of a pyrimidine for Transversion- exhange of a pyrimidine for
a purine or vice versaa purine or vice versa– Missense mutation- changes one amino Missense mutation- changes one amino
acid in polypeptide chainacid in polypeptide chain– Nonsense mutation- creates a stop codon Nonsense mutation- creates a stop codon
in the middle of the polypeptide chainin the middle of the polypeptide chain– Splice site mutations- alters the splicing of Splice site mutations- alters the splicing of
the pre-mRNAthe pre-mRNA
Types of Mutation Types of Mutation (cont)(cont) Frameshift mutations- move the Frameshift mutations- move the
reading frame; can be point reading frame; can be point mutations; all amino acids after mutations; all amino acids after mutation can be affectedmutation can be affected– Insertion- addition of basesInsertion- addition of bases
Tandem duplication- repetition of a Tandem duplication- repetition of a sequence placed very close to the sequence placed very close to the originaloriginal
– Deletion- removal of basesDeletion- removal of bases
Expanding RepeatsExpanding Repeats
Repeated section of Repeated section of DNA is replicated DNA is replicated incorrectly causing incorrectly causing extra repeatsextra repeats
Repeats are added to Repeats are added to during every during every generation (higher generation (higher severity; earlier onset)severity; earlier onset)
Repeats often create Repeats often create symptoms when they symptoms when they reach higher than 40reach higher than 40
Wild type"Normal Gene"
THE ONE BIG FLY HAD ONE RED EYE
Missense THQ ONE BIG FLY HAD ONE RED EYE
Nonsense THE ONE BIG
Frameshift THE ONE QBI GFL YHA DON ERE DEY
Deletion THE ONE BIG HAD ONE RED EYE
Duplication THE ONE BIG FLY FLY HAD ONE RED EYE
Insertion THE ONE BIG WET FLY HAD ONE RED EYE
Expanding (P) THE ONE BIG FLY HAD ONE RED EYE
Expanding(F1) THE ONE BIG FLY FLY FLY HAD ONE
RED EYE
Expanding(F2) THE ONE BIG FLY FLY FLY FLY FLY FLY
HAD ONE RED EYE
Other Causes of Other Causes of MutationsMutations PseudogenesPseudogenes
– Replicate of gene made at earlier timeReplicate of gene made at earlier time– Currently not used (collected enough Currently not used (collected enough
mutations)mutations)– May still be close enough to cross over May still be close enough to cross over
with real gene causing mutations in real with real gene causing mutations in real genegene
Transposons (jumping genes)Transposons (jumping genes)– Jump into working gene causing mutationJump into working gene causing mutation
Minimizing the Effects Minimizing the Effects of Mutationof Mutation
PositionPosition– Change in third position often does nothingChange in third position often does nothing– Change in second position often either does nothing Change in second position often either does nothing
or changes one amino acid for a similar oneor changes one amino acid for a similar one Conditional mutationConditional mutation
– Mutation only affects the Mutation only affects the
phenotype under certain phenotype under certain
conditionsconditions Stem cell DNAStem cell DNA
– Stem cell may retain old template DNA strands and Stem cell may retain old template DNA strands and send new strands into progenitor cellsend new strands into progenitor cell
DNA Repair: DNA Repair: PhotoreactivationPhotoreactivation
DNA is damaged by UVB DNA is damaged by UVB wavelengthswavelengths
Forms thymine dimersForms thymine dimers– extra covalent bond between thymines extra covalent bond between thymines
next to each other on the same strandnext to each other on the same strand– forms kinks in DNA; disrupts replication forms kinks in DNA; disrupts replication
and transcriptionand transcription Enzymes called photolyases absorb Enzymes called photolyases absorb
energy from light and break these energy from light and break these bondsbonds
Humans do not use thisHumans do not use this
DNA Repair: Excision DNA Repair: Excision RepairRepair Enzymes snip out section with pyrimidine Enzymes snip out section with pyrimidine
dimersdimers DNAP fills in gap with correct nucleotidesDNAP fills in gap with correct nucleotides Humans have two typesHumans have two types
– Nucleotide excision repairNucleotide excision repair Used for many types of damageUsed for many types of damage Repairosome- group of enzymes that cut out and Repairosome- group of enzymes that cut out and
replace up to 30 nucleotidesreplace up to 30 nucleotides
– Base excision repairBase excision repair Used for oxidative damageUsed for oxidative damage Replaces up to 5 nucleotides at a timeReplaces up to 5 nucleotides at a time
DNA Repair: Mismatch DNA Repair: Mismatch RepairRepair
Repairs errors Repairs errors that occur that occur because of because of replicationreplication
Enzymes look for Enzymes look for loops in DNA (sign loops in DNA (sign of mismatching) of mismatching) and cut out and and cut out and repair basesrepair bases