Chapter 13 Gene Mutations Transposable Elements and DNA Repair 13 1 Mutations Are Inherited Alterations in the DNA Sequence A Mutation an inherited change in genetic information the descendants may be cells or organisms B The Importance of Mutations 1 Mutations are the source of all genetic variation yet they can have detrimental effects 2 Mutations can be useful for finding or creating mutations that affect different components of a biological system and studying their effects can help understand the system C Categories of Mutations 1 Somatic mutations arise in somatic tissues i When a somatic cell with a mutation undergoes mitosis the mutation is passed to daughter cells a The earlier in development the mutation occurs the larger the clone cells b Many mutations but not many phenotypic effects 2 Germ line mutations arise in cells that produce gametes i Can be passed to future generations in their somatic and germ line ii Gene mutations Small DNA lesion that only affects a single gene a Can only be observed by phenotypic effects iii Chromosome mutations are large scale mutations that affect the number or structure of chromosomes a Can be observed by looking at the chromosomes in the microscope 1 Base substitution the alteration of a single nucleotide in DNA i Transition a purine is replaced by a different purine or a pyrimidine is replaced D Types of Gene Mutations by a pyrimidine by a purine ii Transversion a purine is replaced by a pyrimidine or a pyrimidine is replaced a The number of possible transversions is twice than the number of transitions but transitions arise more often 2 Insertions and Deletions the addition or the removal of one or more nucleotide pair i Insertions and deletions that encode proteins may lead to frameshift mutations changes in a reading frame a Frameshift mutations usually alter all amino acids encoded by nucleotides following the mutation and drastically change phenotype In frame insertions and deletions consisting of any multiple of three nucleotides will leave the reading frame intact but may affect the phenotype ii 3 Expanding trinucleotide repeats the number of copies of a trinucleotide increase in number i The number of copies often correlates with the severity of age of onset of the disease a When more repeats are present the probability of expansion to even more repeats increases b How an increase in the number of trinucleotides produces disease symptoms is not yet understood E Phenotypic Effects of Mutations 1 Forward mutation a mutation that alters the wild type allele 2 Reverse mutation changes the mutant allele back into the wild type allele 3 Missense mutation a base substitution that results in a different amino acid in a protein 4 Nonsense mutation changes a sense codon one that specifies an amino acid into a nonsense codon one that terminates translation 5 Silent mutation creates a different DNA sequence that specifies the same amino acid as a wild type sequence does thanks to the redundancy of the genetic code 6 Neutral mutation a missense mutation that alters the amino acid sequence of the protein but does not change its function 7 Loss of function mutations cause the complete or partial absence of normal protein function i Alters the structure of a protein that the protein no longer works correctly ii The mutation can occur in regulatory regions that affect the transcription translation or splicing of the protein iii They are frequently recessive and an individual diploid organism must be homozygous for a loss of function mutation before the effects are exhibited 8 Gain of function mutations produces an entirely new trait or it causes a trait to appear in an inappropriate tissue or at an inappropriate time in development 9 Condtional mutations are expressed only under certain conditions 10 Lethal mutations cause premature death 1 Suppressor mutations a genetic change that hides or suppresses the effect of another i Intragenic suppressor mutation in the same gene that contains the mutation being suppressed It may change a second nucleotide in the same codon a b By suppressing a frameshift mutation 1 Such as a deletion then an addition c It may make compensatory changes in the protein by folding the polypepetide chain ii Intergenic suppressor mutation occurs in a gene other than the one bearing the original mutation a Sometimes work by changing the way that mRNA is translated F Suppressor Mutations mutation G Mutation Rates mutant allele 1 Mutation rate the frequency with which a wild type allele at a locus changes into a i Generally expressed as the number of mutations per biological unit a Spontaneous mutation rates are low for all organisms studied b Eukaryotic mutation rates is higher than prokaryotic mutation rates 1 Due to the fact that the rates are calculated per gamete and several cell divisions are required to produce a gamete whereas prokaryotic mutation rates are calculated per cell division 13 2 Mutations Are Potentially Caused by a Number of Different Natural and Unnatural Factors A Spontaneous mutations a result of natural changes in DNA structure B Induced mutations result from changes caused by environmental chemicals or radiation C Spontaneous Replication Errors 1 Mispairing may occur through wobble in which normal protonated and other forms of 2 bases are able to pair because of the flexibility of DNA helical structure Incorporated error when a mismatched base has been incorporated into a newly synthesized nucleotide chain 3 Replicated error creates a permanent mutation because all of the base pairings are 4 Strand slippage can occur when one nucleotide strand forms a small loop i If looped out nucleotides are on newly synthesized strand an insertion results a Next during replication the insertion will be in both strands ii And if on the template strand then there is a deletion that will be perpetuated during replication iii Unequal crossing over produces no net change in the number of nucleotides 5 Unequal crossing over results in one DNA molecule with an insertion and the other with a deletion 6 Both strand slipping and unequal crossing over produce duplicated copies of sequences which in turn promote further strand slipping and unequal crossing over D Spontaneous Chemical Changes 1 Depurination the loss of a purine base from a nucleotide which results when a covalent bond connecting the purine to the 1 carbon atom of the deoxyribose sugar breaks producing an apurinic site a nucleotide that lacks its purine
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