The molecular basis of mutation mutations may result

The Molecular Basis of Mutation
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mutations may result from single base-pair
changes
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the addition or deletion of base pairs
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the insertion of a transposable genetic element in a gene
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they may also arise when an array of repeated trinucleoties expands
Tautomeric Shifts
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hydrogen atoms can move from one position in a purine or pyrimidine to
another position
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example: an amino group to a ring nitrogen
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the more stable keto forms a thymine and guanine
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the amino forms of adenine and cytosine
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may frequently undergo tautomeric shifts to less stable enol and imino forms
Recessive Mutation
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often block metabolic
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shifts of H-atoms between the #3 and #4 position of pyrimidines
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shifts of H-atoms between the #1 and #6 positions of the purines

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Tautomeric Shifts and Base Pairing
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although tautomeric shifts are rare, they may be of considerable
importance in DNA metabolism because some alter the pairing potential of
bases
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the more stable kept forms of T and G and the amino forms of A and C may
infrequently undergo tautomeric shifts to less stable enol and imino forms
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the bases would be expected to exit in their less stable tautomeric forms for
only short periods of time
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if a base existed in the rare form at the moment it was being replicated or
being incorporated into a nascent DNA chain, a mutation would result
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Hydrogen bonded A:C and G:T base pairs that form when cytosine and
guanine are in their rare amino and enrol tautomeric forms
Tautomeric Shifts Cause Mutations
1. Guanine undergoes a tautomeric shift to its rare
enol form (G*) at the time of replication
2. in its enol form, guanine pairs with thymine
3. During the subsequent replication, the guanine
shifts back to its more stable kept form
4. The thymine incorporated opposite the enol form
of guanine directs the incorporation of adenine
during the next replication
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the net result is a G:C to A:T base-pair substitution
Base Substitutions
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12 different base pair substitutions can occur in DNA
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4 possible transitions and 8 possible transversions
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Transition - replaces a pyrimidine with another pyrimidine or a purine
for another purine
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Transversion - replaces a pyrimidine with a purine or a purine with a
pyrimidine
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base substitutions can lead to different changes in amino acids
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Silent Mutation - single base pair mutation that does not lead to change
in the amino acid
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Mis-sense Mutation - single base pair mutation that lead to a different amino acid
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Non-sense Mutation - mutation that results in a stop codon, leading to truncated polypeptide
Frameshift Mutations
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base-pair additions and deletions within the coding regions of genes are collectively referred
to as frameshift mutations because they alter the reading frame of all base-pair triplets in the
gene that are distal to the site at which the mutation occurs
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a mutant gene is produced by the insertion of a C:G base pair between the 6th and 7th base
pairs of the wild-type gene
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the insertion alters the reading frame of the gene distal to the mutation, relative to the
direction of transcription and translation
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the shift in reading frame, in turn, changes all of
the codons in the mRNA and all of the amino acids
in the polypeptide specified by base-pair triplets
distal to the mutation

MBG 2040