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When a mutation substitutes for a single codon, which position is most likely to change the amino acid associated with that codon? Why is that?

User Safa
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In most cases the codons encoding for a specific amino acid differ only by a single nucleotide (typically the third one). However, serine is unique among the 20 amino acids in that it is encoded by two disjoint sets of codons that require a tandem substitution of two nucleotides to switch between the two sets, one comprised of the codons TCT, TCC, TCA and TCG (TCN, denoted set S′) and the other set includes only two codons - AGT and AGC (AGY, denoted set S′′)1. The two sets of codons encoding serine cannot be connected through a single point mutation1. The serine’s codon structure allows it to participate in two separate substitution patterns, each of which conserves different amino acid characteristics. The S′′ single mutation transition substitution category includes the amino acids serine, in addition to transition neighbors2,3,4 glycine (G), and asparagine (N). In contrast, the S′ single mutation transition substitution category includes serine, proline (P), and alanine (A)3,5,6 (Fig. 1). The substitution of S′ to amino acids P and A occur by a single mutation at the first codon position. The substitution from serine to threonine (T) is not included either of the substitution sets, as it can be a result of a single nucleotide change from either S′ of S″. While the amino acid substitution derived from S′ are enriched in conserved β-turns3,6,7, those derived from S″ are generally of a neutral hydrophobicity (i.e., amino acids that are neither strongly hydrophobic or hydrophilic)3,6.

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User Sophana
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