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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