GCD 3022 1st Edition Lecture 27 Outline of Last Lecture I Mutations a Allelic variation b Types of mutations i Chromosome mutations ii Genome mutations iii Gene mutations c Types of cells i Germ line ii Somatic II Mutations that change DNA sequence a Point mutations i Base substitution ii Transition iii Transversion iv Addition or deletion III Mutations that alter the coding sequence a Silent mutations b Missense mutations These notes represent a detailed interpretation of the professor s lecture GradeBuddy is best used as a supplement to your own notes not as a substitute c Nonsense mutations d Frameshift mutations IV Mutations outside of the coding sequence a Up mutations b Down mutations V Effects on genotype and phenotype a Mutations that affect wild type phenotype i Forward and reverse mutations ii Deleterious and lethal mutations iii Beneficial mutations iv Conditional mutations b Suppressor mutations i Two types VI Chromosome mutations a Chromosomal breakpoint b Position effect Outline of Current Lecture I Nature of mutations a Different theories of mutation patterns b Spontaneous mutations c Induced mutations II Mutation rates and frequencies a Mutation rate b Mutation frequency c Ames test III DNA repair a General process b Base Excision Repair BER c Nucleotide Excision Repair NER d Mismatch repair systems i DNA polymerases ii Important traits iii Mechanism e Recombination i DNA double strand breaks ii Chromosomal rearrangements iii DNA double strand break repair Current Lecture I Nature of mutations a Different theories of mutation patterns i Jean Baptiste Lamarck suggested that mutations occurred as a result of use or misuse of certain physiological traits ex disuse of a tail in humans resulted in mutations that got rid of that feature He suggested that these mutations occurred quickly in the time span of only a few generations ii The other hypothesis was that mutations are random implying that genetic variation occurs by chance This is also referred to as natural selection b Spontaneous mutations result from abnormalities in cellular or biological processes The underlying cause of these mutations originates within the cell c Induced mutations caused by environmental agents Agents that alter DNA structure are called mutagens can be chemical or physical agents Mutagens are often involved in the development of human cancers carcinogens and can cause gene mutations that may have harmful effects on future generations II Mutation rates and frequencies a Mutation rate the likelihood that a gene will be altered by a new mutation Usually expressed as the number of new mutations in a given gene per cell generation about 10 5 to 10 9 per generation Mutation rate can be increased or decreased based on the presence or absence of mutagens b Mutation frequency number of mutant genes divided by the total number of genes in a population ex out of 1 million bacteria 10 were mutant mutation frequency 10 5 Frequencies can be greater than rates due to natural selection and genetic drift Important statistic in population genetics c Ames test used to determine if an agent is a mutagen Using a strain of bacteria that cannot synthesize histidine and has a point mutation in a gene involved in histidine synthesis A second mutation may occur that restores the ability to produce histidine The test monitors the rate at which the second mutation occurs III DNA repair a General process detection removal of abnormal DNA synthesis of normal DNA b Base Excision Repair BER certain enzymes recognize an abnormal base and cleave the bond between it and the sugar in the DNA so only the base is removed Then other enzymes come in and repair the site c Nucleotide Excision Repair NER can repair thymine dimers and chemically modified bases This type of repair is found in all prokaryotes and eukaryotes but is better understood in prokaryotes d Mismatch repair systems can find and correct a base pair mismatch i DNA polymerases have a 3 to 5 proofreading ability that can detect base mismatches and fix them This system comes in as a back up in case proofreading fails ii Important traits these systems are specific to the newly made strand and are found in all species The proteins involved in this system can distinguish between the newly made and daughter DNA strand iii Mechanism the mechanism studied in E coli is as follows 1 Prior to replication both DNA strands are methylated but immediately after replication only the parental strand remains methylated 2 Three proteins detect the mismatch and direct its removal from the newly made strand 3 The mismatch sequence is removed and the strand is repaired e Recombination i DNA double strand breaks the breaking of a chromosome into pieces Very dangerous and can occur as a result of ionizing radiation and chemical mutagens or reactive oxygen species byproducts of cellular metabolism ii Chromosomal rearrangements can be caused by double strand breaks and may be repaired by two mechanisms iii DNA double strand break repair two systems are known to repair these damages 1 Homologous recombination repair HRR 2 Nonhomologous end joining NHEJ