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Some of the Different Types of Mutations at the Molecular Level

Mutations occur every day within our bodies without us even knowing them. Outlined here are the three categories of mutations that can occur: Synonymous, Missense, and nonsense. Synonymous mutations cause no changes in protein expression while missense and nonsense can have detrimental consequences to the organisms gene expression and also to the fitness or the individual.

Mutations constantly occur in our bodies every day and can have disastrous consequences if they occur in the wrong region. When Mutations are afflicted upon DNA the concern is where they will occur. This is because DNA primarily contains coding and non-coding regions which are used for functional mRNA or removal respectively. When a mutation occurs in a functional region of DNA three scenarios affect translation in the following ways:

1. A synonymous mutation can occur in which a base is changed without actually changing the amino acid. This is also known as a silent mutation.

2. A missense mutation can occur where a base is substituted with another causing a change in amino acid. There are two sub categories to this type of mutation, conservative and non-conservative. In a conservative missense mutation the correct amino acid will be exchanged with a chemically similar one such as Arginine to Lysine. In a non-conservative missense mutation an amino acid is substituted with another amino acid that is not chemically similar such as Isoleucine to Aspartate.

3. The final type of common mutation is a nonsense mutation, which occurs when a base is changed so that when translation occurs the stop codon is initiated prematurely.

            Out of the three basic types of mutations the nonsense mutation is the most impactful to the organism because if the elongation sequence in translation is terminated early due to the stop codon, then there is a higher chance of a nonfunctional protein being produced. However if the nonsense mutation occurs near the end of the translation process, a viable protein may still be produced.

            Missense mutations are generally unfavorable but can sometimes lead to a more efficient protein. This is can result in positive selection for the organism, meaning its fitness rate (dN/dS) is greater than 1, where the fitness rate measures and organisms preparedness for survival and reproduction. A “1” implies that neutral selection has occurred in the organism or no change at all. Organisms that experience mutations that are detrimental to gene expression have fitness rates below 1, indicating they are less fit for survival and may undergo purifying selection.

            Synonymous mutations are the most common and actually occur quite often. These mutations are able to occur, bypassing repair systems because they are seen as silent mutations, meaning they do not cause any changes to the organisms gene expression allowing function to be conserved across generations.

            So how are these mutations caused? The most common causes are chemicals in the cellular environment that can alter the molecular structure of the bases. Another source of molecular damage is ultraviolet light from the sun which causes the dimerization of adjacent Thymine or Cytosine nitrogenous bases. Mutations can be brought about in the laboratory too through the use of alkylating and intercalating agents. Ethyl methanesulfonate (EMS), for example can be used to add alkyl chains on carbonyl oxygen’s of Thymine or Guanine resulting in a base transversion.

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