PowerPoint PresentationGENIC MUTATIONSSlide 3Slide 4Slide 5Slide 6Slide 7Slide 8Slide 9Slide 10Slide 11Slide 12Slide 13Slide 14Slide 15Slide 16Slide 17Slide 18Slide 19CHROMOSOMAL MUTATIONSSlide 21Slide 22Slide 23Slide 24Slide 25Slide 26Slide 27Slide 28Importance of MutationSlide 30IV. Measuring Genetic VariationSlide 32Slide 33Gel electrophoresisAllozymesPCR: Polymerase chain reactionSlide 37Microsatellites 2-9bpMicrosatellite LocusMicrosatellite Gel with Six IndividualsAlaskan Sled DogsMarkers in the genome are linked to specific breedsSlide 43Sequencing DNAPhylogenetic TreesSlide 46Slide 47I. Producing Genetic VariationGENIC MUTATIONSA. How do new alleles arise?1. Mistakes that occur during the DNA replication process2. Caused by the failure of one of the DNA repair mechanisms3. Ultimate source of genetic variabilityB. Point Mutations1. Single base pair substitutionsA instead of GNot repaired by proofreading or mismatch repairAfter synthesis, new alleles exist.TransitionsPurinesPyrimadinesPurinesPyrimadinesTransversions2. Insertions or deletionsDinucleotide repeat-(CT)n-Formed by slippageBasis of microsatellite allelesC. Consequences of point mutations--changes at specific sites within a gene1. Silent substitutions-single nucleotide changes that do not change the amino acid encoded by the mRNA-usually involve changes that will affect the third position of mRNA codons (wobble degeneracy) -about 70% of point mutations are silent-result in NEUTRAL mutations -NEUTRAL mutations can increase in frequency from one generation through the next through genetic drift.Degeneracy of the code yields many opportunities for silent substitutions2. Missense mutations-single nucleotide changes that do change the amino acid that will be coded (1st or 2nd position changes)-create what are called null alleles-such mutations are usually recessive and deleterious or lethal-occasionally such mutations create beneficial alleles = New AdaptationsExample sickle cell anemiaSingle base pair substitution changes Glutamic Acid to Valine and produces non-functional hemoglobin proteinIs lethal in homozygous conditionHeterozygotes are favored in regions with malaria3. Nonsense mutations-changes in DNA that result in insertion of a premature stop codon into mRNAATT = UAA, ATC = UAG, ACT = UGAEarly stop signal in mRNAHalts translationProtein is non-functional4. Frameshift mutations-addition or deletion of one or a few nucleotides-causes a shift in the reading frame of the mRNA that will be transcribed-all codons downstream of the indel will be changed-results in production of a non-functional proteinD. Mutation Rates1. Spontaneous mutations-mutations occur by chance at a low frequency-about 10-9 or 1 per billion nucleotides replicated in mammals-spontaneous mutation rate varies among genes and among speciesDrosophila -- brown eye: 3 x 10-5Humans -- retinoblastoma: 2 x 10-5Recurrent mutations are mutations that arise repeatedly. Albinism in mice is a recurrent mutationWild type to albino = 10-5/gamete/generation2. Induced mutations-mutagens are substances that increase the mutation rate above the spontaneous rate- Ultra-violet light- Ionizing radiation - Pesticides and industrial chemicalsE. Mutation is a random event.1. Mutation RATES are affected by the environment.2. Mutation is NOT directed with respect to environment. -Exposure to mutagens will increase overall mutational rate, but not determine which particular genes will be affectedCHROMOSOMAL MUTATIONSII. Mutations of large effectA. How do mutations cause changes in genomes?1. Karyotypic mutations- mutation results in changes in more than one chromosome. 2. Chromosomal mutations- mutations results in changes in more than one gene on the SAME chromosome.B. Karyotypic mutations1. Polyploidy-entire sets of chromosomes duplicate-can occur by two different mechanisms1) Allopolyploidy--the duplicate sets of chromosomes come from two distinct sources2) Autopolyploidy--the duplicate sets of chromosomes come from the same sourceSpecies A Species BF1 HybridAllotetraploidAllotetraploids AutotetraploidsXSpecies A Species AF1 TriploidAutotetraploidX2N NAuto- and Alloploidy in the Evolutionary History of Xenopus FrogsAutotetraploidDiploidModified TetraploidAllotetraploidC. Chromosomal mutations1. Duplications-piece of a chromosome is duplicated; can involve one or multiple genes-caused by replication errors or unequal crossing over; something gets copied twice-unequal crossing over in meiosis1) Homologues don’t pair properly so after crossing over, one chromosome has a deletion and the other has a duplication2) Occurs rather easily if DNA contains many tandemly repeated nucleotides or genesThought to be important mechanism in the evolutions of multigene families: Hemoglobin gene familyHigh structural similarity of transcriptional units among lociDifferent functions due to different timing of expressionImportance of MutationIII. Mutation as an Evolutionary ForceA. Mutagenic change in populations1. Mutation is NOT a STRONG evolutionary force because it does not cause a big change from one generation to the next -probability of survival of a rare mutant is low-survival of a rare mutant is higher if recurrent mutation-survival probability of a rare mutant is higher if 1) mutant is favored by natural selectionand 2) populations is rapidly increasing in sizeB. Importance of mutation as an evolutionary force1. Mutation creates variation-the only source of unique alleles-rate of accumulation of mutant variation can be fairly high for polygenic traits2. Mutation provides the variation needed by other forces of evolution-neutral alleles are acted upon by genetic drift -advantageous and disadvantageous alleles are acted upon by natural selectionIV. Measuring Genetic VariationA. Natural populations1. Classic view-natural populations harbor very little genetic variation2. Since mid-1960s-natural populations have been shown to harbor enormous amounts of genetic variationAllozyme heterozygosities show high levels of genetic variationB. Determining genotypes1. From phenotype (but this is often rare)-measuring response-can be used for single locus codominant traits-allozymes: allelic variants of enzymes2. From genotype-Scoring nucleotide size of alleles-Determining DNA sequence of allelesGel electrophoresis-+Direction of movementProteins and DNA are negatively chargedBands move from negative to positive charges within the electrophoresis rigSmaller sizes move more