Журнал клинической и медицинской геномики

Mitochondrial Genomes and Frameshift Mutations: Hidden Stop Codons, their Functional Consequences and Disease Associations

Abstract

Tiratha Raj Singh

Reprogramming of mRNA translation by localized alterations in the standard translational rules is termed as recoding. Frameshifting is one class of recoding and defined as protein translations that start not at the first, but either at the second (+1 frameshift) or the third (-1 frameshift) nucleotide of the codon. Apparently, most frameshifts would yield nonfunctional proteins. Therefore frameshifts lead to waste of energy, resources and activity of the biosynthetic machinery. In addition, some peptides synthesized after frameshifts are most likely cytotoxic. Coding sequences lack stop codons, but many stop codons generated due to frameshifted sequences, termed off-frame stops or hidden stop codons. These hidden stops terminate frame-shifted translation, potentially decreasing energy, and resource waste on nonfunctional proteins. Frameshift mutations for the sake of mitochondrial genomes were evaluated and results support this putative ancient adaptive event for the selection of codons that can be part of hidden stop codons. Mitochondrial genomic data analyses support this fact as most of the correlations between hidden stops and various functional and evolutionary parameters were positive. Association of frameshift mutations with many diseases is also being studied to represent the biological significance of this putative event. It is estimated that this kind of study will reveal momentous correlation between frameshift mutations and their biological consequences.