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The following table lists the chemical properties of the 20 amino acids that commonly appear in proteins. These are the amino acids that are specified by DNA/RNA using the genetic code as defined in Table 4.1. All amino acids have the same backbone, but they have side chains with different chemical properties as described in Table 4.2. These chemical properties are referred to as polar, non-polar, hydrophobic, acidic, basic, aromatic, or having other special properties. The chemical properties of the amino acid are key to performing the function of the protein.

Table 4.2. Chemical properties of amino acids based on their side chains.

Chemical group	Amino acids
Hydrophobic (non-polar, uncharged)	Alanine, leucine, isoleucine, methionine, phenylalanine, tryptophan, tyrosine, valine
Polar (uncharged)	Serine, threonine, asparagine, glutamine
Aromatic	Tryptophan, phenylalanine, tyrosine
Basic (positively charged)	Lysine, arginine, histidine
Acidic (negatively charged)	Aspartic acid and glutamic acid
Special properties	Cysteine, proline and glycine

If the amino acid has profoundly different chemical properties, this can change or even destroy the function of the protein. For example, the MC1R gene (also known as melanocortin 1 receptor), is responsible for pigment production in melanocytes (Chapter 7 on the Extension locus). There are two well-known variants of this gene, one associated with the production of red pigment and another with the production of black pigment. The differences are the result of a substitution of a T for a C in one of the codons (Marklund et al., 1996). The situation is illustrated in Fig. 4.2 taken from the paper of Marklund et al. (1996).

Fig. 4.2. This figure is taken from Marklund et al. (1996) and shows the alignment for two alleles in a region of the gene MC1R, the variant in codon 83 responsible for the difference between the E and e allele and the resulting amino acid change at position 83 from serine to phenylalanine (the amino acids are listed in the figure using three-letter codes for each amino acid).

This is called a non-synonymous mutation because it changes an amino acid. Furthermore, the change is chemically significant because phenylalanine is hydrophobic while serine is hydrophilic. Changing the amino acids in this position destroys the binding site of this receptor and, as a consequence, it cannot interact with melanocyte-stimulating hormone to create black pigment. The default pigment is red. When non-synonymous variants are found, one of the major questions is what impact this may have on gene function. Proof could come from doing gene editing and cell biology experiments. However, these experiments are costly, time-consuming, and not justifiable for every genetic variant that is discovered. Therefore, scientists turn to computer modeling to make predictions about the effects of a mutation.

Several of the more popular programs are SIFT (Kumar et al., 2009) and Polyphen-2 (Adzhubei et al., 2010) for simple substitutions and Provean for simple substitutions, deletions, and insertions (Choi et al., 2012). These programs assess the likelihood that changes in amino acids will alter protein function based on the physical and chemical properties of the amino acids. Scientists can enter the different series of amino acids associated with the two variants and the programs will return a prediction as to whether the variant will have no effect, a possible deleterious effect, or a probable deleterious effect.