Introduction

As we have seen, the cell invests a huge amount of effort to ensure that the nucleotide sequence of each and every DNA molecule is maintained as accurately as possible. On some occasions, however, errors or changes in the sequence of nucleotides take place. These errors are referred to as a ‘mutation’. There are several different types of mutations; we will explore each one and the impact they have on the expression of genes.

Learning

DNA Mutations

Mutations can be caused by a variety of factors, including:

• Simple errors during DNA replication – approximately 1 out of every 100,000 nucleotides is placed incorrectly
• Radiation – can cause breaks in DNA chains.
• Toxic chemicals – can alter the accuracy of DNA replication.

In most cases, however, our cells have developed a robust mechanism for fixing the DNA chain.  Different versions of the DNA polymerase enzyme are responsible for recognizing mismatched nucleotides, removing them and re-copying the DNA strand to restore the correct sequence.  It is through the collective effort of these repair enzymes that most human DNA will contain only 1 mistake for every 1 billion nucleotide pairs (or fewer than 1 mistake per each chromosome).

There are several types of mutations; each type has a different impact on the gene where the mistake occurs. And while we often think of mutations as bad things it’s important to remember that their result can be good as well. Let us look at these mutation types now.

Nucleotide Substitution

In a substitution error, during DNA replication, the DNA polymerase enzyme may mis-read the template DNA strand and mistakenly incorporate the wrong matching nucleotide into the new chain.

For example, if the template strand contains the sequence:

• –GAGG-

On the new chain, we would expect the sequence:

• –CTCC-

However, if an error is made where an ‘A’ is mistakenly inserted for the ‘T’, we wind up with:

• –CACC-

Then during future replication, this would result in new DNA strands containing the sequence:

• -CACC-
• -GTGG-

So what had been –GAGG- is now –GTGG-. Consider that the code for the assembly of proteins is stored in the sequence of nucleotides as we discussed previously. Within a protein-encoding gene, each triplet (or three nucleotides in sequence) contains the information to specify a single amino acid. To illustrate this, consider the following analogy where we have a sentence (protein) composed of a series of three letter words (amino acids). It is the sequence of letters (nucleotides) that defines the word at each spot.

THE BAD CAT SAW THE BIG DOG AND RAN AND BIT HIM

If a substitution mutation were to occur where the middle letter of the word ‘SAW’ was altered, we might find something like this:

THE BAD CAT SEW THE BIG DOG AND RAN AND BIT HIM

In this instance, while the meaning of the word ‘SAW’ was altered to ‘SEW’, the rest of the sentence structure remains intact. Simple substitution mutations can have similar impacts on the production of proteins from a gene, a small deviation but leaving the protein largely intact. The resulting protein may function essentially as it used to, it may have reduced functionality, or it could even gain new/better functioning.

Insertion Mutation

In an insertion mutation, an additional nucleotide is inserted mistakenly into a DNA region as shown:

Going back to our sentence analogy, an insertion mutation might result in the following:

THE BAD CAT SAN WTH EBI GDO GAN DRA NAN DBI THI M

Notice what has happened; by inserting an ‘N’ into the word ‘SAW’, we have altered the sequence of three-letter words and disrupted the meaning of the sentence.  This would be a much more significant type of mutation that would result in an overall alteration in the function of a protein and possibly a complete loss of function.

Deletion Mutation

In a deletion mutation, one or more nucleotides are mistakenly deleted from a DNA chain. Similar to an insertion mutation, when this occurs, the entire function of a protein may be completely altered often for the worse.

Using our sentence analogy, a deletion mutation resulting in the removal of three letters from the sentence may result in the following:

THE BAD AND RAN AND BIT HIM

Note the removal of the letters ‘CAT SAW THE BIG DOG’ from the beginning of the section.  While this deletion has altered the overall meaning of the sentence, the rest of the sentence structure remains intact.

Other Mutation Types

Two additional mutation types can occur where large fragments of DNA are altered.

In an inversion mutation, a large segment of DNA is cut, flipped and re-inserted into the same DNA strand. As you can imagine, this type of mutation has a disruptive impact on the function of a gene.

The final type of mutation we will cover is the translocation mutation.  In a translocation mutation, a fragment of DNA is cut from one chromosome and then re-inserted into another chromosome.  This type of mutation is very disruptive as it ultimately has the potential to disrupt multiple genes on different chromosomes.

Summary

In this section, we have learned:

• DNA mutations can occur as a result of:
  • Errors during Replication
  • Radiation
  • Toxic chemicals
• There are several different types of mutations can occur, including:
  • Substitution Mutation
  • Insertion Mutation
  • Deletion Mutation
• Larger-scale mutations involving alterations to entire segments of a chromosome include:
  • Inversion Mutation
  • Translocation Mutation
  • While mutations can have harmful effects, some may be beneficial!