gene mutations 25-4

GENETICSGENETICSGenetics is the study of the transmission of Genetics is the study of the transmission of thingsthings from one generation to the nextfrom one generation to the next

Genetic characteristics of a population can change Genetic characteristics of a population can change over timeover time– ““Evolution”Evolution”

These These thingsthings can be can be– Traits / characteristicsTraits / characteristics– ChromosomesChromosomes– GenesGenes

GENETIC VARIATIONGENETIC VARIATIONGenetic variation is produced in two waysGenetic variation is produced in two ways

– through Mutationthrough MutationHeritable changes in DNA sequenceHeritable changes in DNA sequence

– Through Gene transferThrough Gene transferAcquiring genes from another member of our speciesAcquiring genes from another member of our species

MUTATIONMUTATIONInheritable change in DNA sequenceInheritable change in DNA sequence

Relatively rareRelatively rare

Generally occur during DNA replication or repairGenerally occur during DNA replication or repair– May also occur in response to mobile DNA May also occur in response to mobile DNA

elementselementsTransposons and virusesTransposons and viruses

May affect gene expressionMay affect gene expression

SPONTANEOUS MUTATIONSSPONTANEOUS MUTATIONSOccur without effects of outside agentsOccur without effects of outside agents

– Radiation, chemical mutagens, etc.Radiation, chemical mutagens, etc.

Various typesVarious types1.1. Base substitutionsBase substitutions

One or more base pairs changedOne or more base pairs changed

2.2. Insertions and deletionsInsertions and deletionsSometimes caused by transposable elementsSometimes caused by transposable elements– Jumping genesJumping genes

Insertion of one or more basesInsertion of one or more basesDeletion of one or more basesDeletion of one or more bases

MUTATIONSMUTATIONSPOINT MUTATIONPOINT MUTATION

One base pair alteredOne base pair alteredSubstitution can change the entire Substitution can change the entire

reading frame of the DNA causingreading frame of the DNA causing

1.1. Silent mutation – no result because same Amino Acid is Silent mutation – no result because same Amino Acid is produced (lucky there was no change)produced (lucky there was no change)

2.2. Missense mutationMissense mutationWrong AA produced which messes up the protein (Sickle Cell Anemia)Wrong AA produced which messes up the protein (Sickle Cell Anemia)

3.3. Nonsense mutationNonsense mutationStop command results, so proteins don’t even get made properlyStop command results, so proteins don’t even get made properly

SubstitutionSubstitution

Insertion MutationsInsertion Mutations

MUTATIONSMUTATIONSInsertions & Deletion MutationsInsertions & Deletion Mutations

““Frameshift mutations”Frameshift mutations”

Insertion or deletion of base pair(s)Insertion or deletion of base pair(s)– e.g., GGA e.g., GGA G GAAGA (gly GA (gly glu) glu)

Generally alter reading frameGenerally alter reading frame– ““Frameshift”Frameshift”– All downstream amino acids alteredAll downstream amino acids altered

Protein function generally affectedProtein function generally affected– Typically “knockout” mutantsTypically “knockout” mutants

Insertion / deletion & genes Insertion / deletion & genes that jumpthat jump

““Transposons” = “Jumping Genes”Transposons” = “Jumping Genes”

Transposons are DNA segments spontaneously entering Transposons are DNA segments spontaneously entering or exiting chromosomesor exiting chromosomes

Transposition into a gene constitutes a large insertionTransposition into a gene constitutes a large insertion– Gene is generally inactivatedGene is generally inactivated

Transposition out of a gene may restore gene functionTransposition out of a gene may restore gene function

TRANSPOSABLE ELEMENTSTRANSPOSABLE ELEMENTS

First discovered by Barbara McClintock in the 1940sFirst discovered by Barbara McClintock in the 1940s

Worked with maize (corn)Worked with maize (corn)

Kernel color varied as DNA sequences jumped in and Kernel color varied as DNA sequences jumped in and jumped out, messing with the pigment genesjumped out, messing with the pigment genes

no pigmentno pigment

partial pigmentpartial pigment

normal pigmentnormal pigment

TRANSPOSABLE ELEMENTSTRANSPOSABLE ELEMENTSDiscovered them in 1940s, but nobody paid attention

Ideas finally accepted in 1970s

Nobel prize in 1983 – She was 81 years old!!

Some of Barbara’s historically significant research plots were destroyed by nutcases protesting genetic engineering– None of the plants were engineered

INDUCED MUTATIONSINDUCED MUTATIONSSome mutations occur spontaneouslySome mutations occur spontaneously– RareRare

Certain chemicals or radiation can cause Certain chemicals or radiation can cause mutationsmutations– We call these “Mutagens”We call these “Mutagens”– Greatly increase the frequency of mutationsGreatly increase the frequency of mutations

e.g., 1,000X or moree.g., 1,000X or more

INDUCED MUTATIONSINDUCED MUTATIONSChemical MutagensChemical Mutagens

Chemicals Chemicals

RadiationRadiation– Ultraviolet Ultraviolet – Ionizing radiationIonizing radiation

(X-rays, gamma rays)(X-rays, gamma rays)Breaks in single strandsBreaks in single strandsBreaks in double strandsBreaks in double strandsMay result in deletions, May result in deletions, insertionsinsertions

DNA REPAIRDNA REPAIR

Mutations are rareMutations are rare– Many errors are automatically corrected by DNA Many errors are automatically corrected by DNA

Polymerase’s spell checking abilitiesPolymerase’s spell checking abilities

Mutations in genes for DNA repair enzymes are Mutations in genes for DNA repair enzymes are particularly problematicparticularly problematic– Increase mutationsIncrease mutations

NORMAL DNA REPAIRNORMAL DNA REPAIRProofreading is always happeningProofreading is always happening– DNA Polymerase detects error during synthesis DNA Polymerase detects error during synthesis – Backs up, excises wrong base, and continuesBacks up, excises wrong base, and continues– Relatively accurateRelatively accurate

Mismatch repair is completedMismatch repair is completed– Recognizes mismatch if DNA polymerase misses itRecognizes mismatch if DNA polymerase misses it– Cuts out incorrect segmentCuts out incorrect segment– Fills in gap correctlyFills in gap correctly– DNA ligase joins the segments DNA ligase joins the segments – Relatively accurateRelatively accurate