Trinucleotide Repeat Disorders - Genetics - Why Three Nucleotides?

Why Three Nucleotides?

An interesting question is why three nucleotides are expanded, rather than two or four or some other number. Dinucleotide repeats are a common feature of the genome in general, as are larger repeats (e.g. VNTRs - Variable Number Tandem Repeats). One possibility is that repeats that are not a multiple of three would not be viable. Trinucleotide repeat expansions tend to be near coding regions of the genome, and therefore repeats that are not multiples of three could cause frameshift mutations. If the frameshift mutations altered the expression of developmentally obligatory pathways, then non-trinucleotide repeats may be masked by developmental lethality. Mutations of 3 base pairs, on the other hand, do not cause a catastrophic frameshift mutation, and unless a stop codon (TAG, TAA, TGA) is the triplet that is added to the gene - which would in almost all cases render the protein coded for useless - a trinucleotide addition to a gene can have no effect at all on the protein, can cripple the protein, or sometimes can make it work even better than it used to. The overwhelming number of mutations are not beneficial, and this article is testimony to the severely detrimental effects trinucleotide additions to the genome can produce. Still, 3 (and multiples of 3) nucleotide expansions to a coding region of the genome are at least somewhat less likely to be detrimental to an organism as a maximum of two amino acids will be affected, and the reading frame otherwise maintained the same.