Bio 301 - Ch 9.1 & 10.4 Book Notes

mutations can change genes in many ways

• mutations provide an opportunity to trace ancestry and investigate the function of genes through manipulation of the DNA sequence

• changes in the DNA sequence of genes by mutation can have a variety of effects on those genes

  • mutations can change the structure & function of the gene’s products

  • mutations can also change the regulation of the gene’s expression

• gene mutations can have important consequences for the microbe

  • it may cause additional resistance to antibiotics that normally target the gene’s product

  • mutation is an important mechanism that can add or subtract genes from genomes

• when the codon is being read by the ribosome, the mechanism does not register if bases have been added or removed through mutations

  • if the number of bases inserted or deleted is not a multiple of three, the reading frame of translation changes

mutations that alter gene sequence fall into several different physical & structural classes

• point mutation is a change in a single nucleotide

  • transition — replacing a purine with a different purine or a pyrimidine with a different pyrimidine

  • transversion — swapping a purine for a pyrimidine

• insertions involve the addition of one or more nucleotides which lengthens the sequence than its original length

  • serves to alter the reading frame of a DNA sequence

• deletions involve the subtraction of one or more nucleotides which shortens the sequence than its original length

  • serves to alter the reading frame of a DNA sequence

• inversion results when a fragment of DNA is flipped in orientation relative to the flanking DNA on either side

• duplication produces a second copy of a sequence fragment on the DNA molecule, usually adjacent to the original copy

• transposition is the movement of a sequence fragment from one location to another

  • these movements are usually catalyzed by special enzymes which can involve insertions, deletions, and duplications depending on the mechanism of transposition

• reversion is a process that restores a mutated sequence to its original sequence

mutations can also be categorized into informational classes on the basis of how they affect the gene product

• silent mutation — a mutation that does not change the amino acid sequence encoded by an open reading frame

  • the changed codon encodes the same amino acid as the original codon

• missense mutation — a point of mutation that alters the sequence of a single codon, leading to a single amino acid substitution in a protein

  • there was a nonsynonymous base substitution

  • this sort of mutation may or may not lead to protein function alterations

  • the outcome will depend on the structural importance of the original amino acid and how close in structure & chemical properties of the replaced amino acid

• missense mutations can result in either conservative amino acid replacements or nonconservative replacements

  • an example of a conservative replacement would be leucine substituted for isoleucine

  • an example of a nonconservative replacement would be tyrosine substituted for alanine

• a missense mutation may decrease or eliminate the activity of the protein or it may make the protein more active / gain a new quality

  • loss-of-function — a mutation that eliminates the function of the gene product

  • gain-of- function — a mutation that enhances the activity or allows new activity of a gene product (eg expanded substrate specificity or gaining a completely different substrate specificity

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• knockout mutation — a mutation that completely eliminates the activity of a gene product

  • these mutations can include multiple-base insertions and deletions & nonsense mutations

• nonsense mutation — a mutation that changes an amino acid codon into a premature stop codon

  • an example of this would be TCA (serine) to TGA which results in a truncated protein

  • these truncations can completely knock out the function of proteins and more so in cases where the mutation occurred early in the reading frame

  • the defective proteins are degraded by cellular proteases

  • these mutations can turn genes into pseudogenes which can be lost from the genome during evolution

• frameshift mutation — a gene mutation involving the insertion or deletion of nucleotides that cause a shift in the codon reading frame

  • these mutations often cause the ribosome to encounter a premature stop codon

  • these mutations can turn genes into pseudogenes

  • if the insertion or deletion involves multiples of three bases, the reading frame is not changed, but one or more amino acids are added or removed

  • duplications within an open reading frame can create repeats of codons and increase the length of the protein product

  • this type of mutation can occur if the length of the duplicated segment is not divisible by three

• inversion mutation — a mutation that flips a DNA sequence

  • the rotation would retain the 5 prime to 3 prime polarity in a new molecule

  • if the inversion occurred within a gene, it would likely change the codons in the area and alter the resulting protein

  • these mutations often involve large tracts of DNA encompassing several genes meaning that if an entire gene with its promotor inverts, the gene will likely remain functional & its encoded protein may very well still be made

  • these mutations occur within a genome as a result of recombination events between similar DNA sequences or as a consequence of mobile genetic elements jumping between areas of a genome

the effects that mutations have on the genome sequence can vary

• mutations can affect both the genotype & the phenotype of an organism

• every mutation causes a change in the genotype regardless of whether the mutation causes a change in the phenotype

  • recall that the phenotype only comprises of observable characteristics like biochemical, morphological, or growth traits expressed

• the size of the mutation does not always correlate with the extent of a phenotypic change (usually dependent on the location instead)

mutations arise by diverse mechanisms

• some mutations can arise spontaneously & despite the high accuracy of the replication machinery, mistakes do occur (at a low rate)

• spontaneous mutations in a genome arise for many reasons

  • an example is tautomeric shifts in the chemical structure of the bases; these shifts involve a change in the bonding properties of amino and keto groups

  • these group forms usually predominate but when an amino acid shifts to an imino group, the base pairing changes

  • tautomeric shifts that occur during DNA replication will increase the number of mutation events

• an example provided of how potentially detrimental tautomeric shifts can be is thymine shifting during replication which results in an AT to GC transition mutation

  • after the second round of replication, the mutation is “fixed” on both DNA strands in the mutant

  • the mutation will be passed onto all the mutant’s progeny

• spontaneous mutations in DNA can also be caused by chemical reaction with water (hydrolysis)

  • an example of this is cytosine spontaneously deaminates to yield uracil which base-pairs with adenine instead of guanine

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