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Wize University Biology Textbook > DNA Replication & Repair

Types of DNA Mutations

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Types of DNA Mutations

Mutations in DNA occur when there is a change in the normal DNA sequence.

Point Mutations or Base Substitutions

The term point mutation means that only one base pair is mutated. Point mutations can arise due to:
  • Errors in DNA replication.
  • Environmental exposure to damaging agents like UV light, radiation, etc.
  • Harmful chemicals/ toxins.
  • Byproducts of normal cell metabolism (e.g. lipid oxidation).

There are 3 types of point mutations:
  • Nonsense mutation: a premature stop codon is introduced into a sequence Example: UGC (Cysteine) --> UGA (stop)
  • Missense mutation: a change to the amino acid sequence Example: UGC (Cysteine) --> UGG (Tryptophan)
  • Silent mutation: no change to the amino acid sequence Example: UGC (Cyteine) --> UGU (Cysteine)
Wize Concept
Mutations can be:
  • BENEFICIAL: improves the fitness of an organism (e.g. resistance to a virus, lactose tolerance)
  • BENIGN: does not change the overall fitness of an organism (e.g. change in eye color or silent mutations)
  • HARMFUL: negatively impacts the fitness of an organism (e.g. development of diseases like cancer and birth defects)


Photo by Jonsta247 / CC BY


Exam Tip
To remember that nonsense mutations cause stop codons, just remember the mnemonic: STOP the NONSENSE!


When a nucleotide is replaced by another this is called a base substitution. Most commonly, point mutations are base substitution.
  • There are two different kinds of substitutions: transitions and transversions.
  • Transitions: purine for purine, pyrimidine for pyrimidine. Example: A for G, C for T.
  • Transversion: purine for pyrimidine and vice-versa. Example: A for T, C for G.

PAGE BREAK

Frameshift Mutations

Other mutations have the potential of causing changes in the reading frame of the nucleotide sequence. These are called frameshift mutations. They can be caused by mutations such as insertions or deletions of fragments of DNA.



Wize Concept
You may not have covered what "reading frame" means yet in your biology course, so here's a quick explanation.
  • The DNA sequence codes for proteins.
  • Every 3 nucleotides codes for one amino acid.
  • Therefore, when nucleic acids are translated into proteins, the triplets of nucleotides that are read can make a huge difference in the outcome of a protein. Example: consider the following sequence: TGTGAA. Reading in triplets, TGT codes for cysteine, while GAA is glutamic acid. So this sequence of amino acids is a cysteine linked to a glutamic acid. Now, consider I insert a random nucleotide in the middle of this sequence: TGTTGAA. Again, reading in triplets from left to right, now this codes for TGT = still cysteine, but the next triplet will be TGA = STOP. Turns out TGA is a stop codon, which tells the cellular machinery to STOP making this protein.
  • Due to this single base insertion, the rest of the protein is now missing.
  • This is an example of an insertion causing a shift in reading frame and a premature stop codon.

Practice: DNA Mutations

You are studying a DNA sequence and find a spontaneous mutation that has occurred, resulting in a nonsense mutation. Which of the following is true?

Practice: Type of Mutation

a) What type of point mutation occurred in the DNA sequence below, substitution, insertion, or deletion?

Initial sequence: 3’ ATGCGATTATCTAGTATT 5’
Mutated sequence: 3’ ATGCGATTATCTAGGTATT 5’

b) Does the mutation cause a frameshift, synonymous, missense, or nonsense mutation in the amino acid sequence?
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Tautomeric Shifts

  • DNA nucleotides have inherent instability = are in equilibrium between 2 forms
  • Thymine & Guanine = keto vs. enol
  • Adenine & Cytosine = Amino vs. imino
  • The equilibrium lies heavy towards the more common form that gives the usual base-pairing C-G & A-T
  • When in their alternate form, the base pairing changes to T-G & C-A
  • Some mutagens, like 5-bromouracil, are in an equal equilibirum between their two forms
  • This makes it equally likely to base pair with G or A
  • A source of single nucleotide polymophisms (SNPs)
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Example: Tautomeric Shifts

Draw the steps showing how a tautomeric shift of cytosine from its amino to its imino form leads to an SNP given the sequence: 5'-TGCT-3'
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DNA Slippage

In highly repetitive regions of the genome, DNA polymerase falls off the template strand and when it comes back together it can do:

Backwards Slippage

  • The newly synthesized strand "slips" backward 1 bp
  • Results in a 1 bp insertion

Forward Slippage

  • The template strand "slips" forward 1 bp
  • Results in a 1 bp deletion

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Copy Number Variations

Individuals have differences in the number of copies of genes or genetic information, having a different number of copies of those genes/gene regions.

Sources of Copy Number Variation:

  • Unequal cross-over during homologous recombination in prophase I of meiosis
  • Non-homologous end joining causing loss of large chromosome regions
  • Mobile elements
Curran919, CC BY-SA 4.0 via Wikimedia Commons
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Mobile Elements

  • Regions of the genome that are considered to be "trapped" viruses
  • Retain the ability to move within the genome, but cannot leave the cell
  • Do NOT increase copy number variations if they just "jump"
  • The increase copy number variations if they move through a copy & paste mechanism

Mobile Elements & Disease

  • Transposons in the human genome are called Alu elements
  • LINEs = Long interspersed elements
  • SINEs = Short interspersed elements
  • Alu elements represent approximately 11% of the human genome = millions of copies!
  • They move through a retrotransposon copy & paste mechanism
  • The "paste" process causes insertional mutagenesis
  • Insertional mutagenesis can disrupt genes, causing changes in gene expression or regulation and can cause recombination events to occur where they shouldn't
  • Diseases attributed to Alu elements: Hemophilia, leukaemia, muscular dystrophy and MANY more!

Extra Practice
The bong mutant of a yeast species Saccharomyces causes them to be restricted to generating ATP through glycolysis alone. Which of the follow statements could be a possible role of this mutation?
Practice: Protein Structure
A missense mutation arises in the amino acid sequence in which the residue R is substituted for A. Which of the following is most likely true?
Which of the following mutations would not affect translation?
Mutation
You are studying the genetic codes of three phenotypically identical E. coli bacteria: HB99, HB100 and HB101. While studying their DNA sequences, you note that a point mutation has in a the same gene in each of the E. coli strains. The gene encodes for an enzyme required to methylate lysine 27 on Histone 3: H3K27.
HB99 sequence: ATGCGTCACGTCGA
HB100 sequence: ATGCGTTACGTCGA
Mutation
You are studying the genetic codes of three phenotypically identical E. coli bacteria: HB99, HB100 and HB101. While studying their DNA sequences, you note that a point mutation has occurred in the same gene in each of the E. coli strains. The gene encodes for an enzyme required to methylate lysine 27 on Histone 3: H3K27.
HB99 sequence: ATGCGTCACGTCGA
HB100 sequence: ATGCGTTACGTCGA
Which of the following mutations would not affect translation?
MCAT Practice Question
The bong mutant of a yeast species Saccharomyces causes them to be restricted to generating ATP through glycolysis alone. Which of the follow statements could be a possible role of this mutation?
A missense mutation arises in the amino acid sequence in which the residue R is substituted for A. Which of the following is most likely true?
Practice: Protein Structure
A missense mutation arises in the amino acid sequence in which the residue R is substituted for A. Which of the following is most likely true?
MCAT Practice Question
The bong mutant of a yeast species Saccharomyces causes them to be restricted to generating ATP through glycolysis alone. Which of the follow statements could be a possible role of this mutation?
A human cell has received a mutation and is unable to produce actin. What would be the result after mitosis?
A cell has a mutation that results in higher expression of the gene encoding p21. What would happen to the cell?
Retinoblastoma is a type of eye cancer caused by:
A. a mutation in the Rb transcriptional factor that its inhibited binding to DNA
B. a mutation in p53 that prevents it from recognition damaged DNA
Which of the following is most likely to occur due to a mutation in p21?
Mutation that leads to the substitution of one amino acid for another are called?
Which of the following is consistent with the observation that cancers have an important epigenetic component?
Some tumor supressor proteins are involved in DNA repair
Some carcinogens are not mutagens
A nonsense mutation in the drosophila bicoid gene would result in which of the following?
After two rounds of DNA replication an SNP has been introduced into a genes open reading frame but the protein product is the exact same as the gene product from the sequence without the SNP. What type of mutation is this?
If a single base pair was inserted into DNA coding for the second exon of a eukaryotic mRNA transcript with three exons and two introns, which of the following statements is most likely true about the resulting protein?
Imagine you are studying an E. coli gene that codes for a specific enzyme. You have isolated a mutant for this enzyme, where E. coli produces a shorter than normal form of the polypeptide, and thus the enzyme is not functional. What type of mutation most likely led to this mutant?
Which of the following are directly responsible for ensuring that cells do not replicate in the event of DNA damage?
Which of the following describes a nonsense mutation?
You discover through your genetic counsellor that you have an alteration in an mitochondrial transit sequence. Which of the following characteristics of your nuclear genome would have been altered?
The bong mutant of a yeast species Saccharomyces causes them to be restricted to generating ATP through glycolysis alone. Which of the follow statements could be a possible role of this mutation?
Which of the following could affect all of the primary, secondary, and tertiary structure
of a protein?
Practice: Protein Structure
A missense mutation arises in the amino acid sequence in which the residue R is substituted for A. Which of the following is most likely true?
Which of the following mutations would not affect translation?
Mutation
You are studying the genetic codes of three phenotypically identical E. coli bacteria: HB99, HB100 and HB101. While studying their DNA sequences, you note that a point mutation has in a the same gene in each of the E. coli strains. The gene encodes for an enzyme required to methylate lysine 27 on Histone 3: H3K27.
HB99 sequence: ATGCGTCACGTCGA
HB100 sequence: ATGCGTTACGTCGA
Which DNA mutation(s) involve changes to a single basepair?