The shiftability of protein coding genes: the genetic code was optimized for frameshift tolerating

Abstract

The genetic code defines the relationship between a protein and its coding DNA sequence. It was presumed that most frameshifts would yield non-functional, truncated or cytotoxic products. In this study, we report that in E. coli , a frameshift β-lactamase (bla) gene is still functional if all of the inner stop codons were readthrough or replaced by a sense codon. By analyzing a large dataset including all available protein coding genes in major model organisms, it is demonstrated that in any species, and in any protein-coding genes, the three translational products from the three different reading frames, are always similar to each other and with constant ~50% similarities and ~100% coverages, and the similarities is predefined by the genetic code rather than the sequences themselves. It is likely that a coding gene can be translated into three isoforms from each of the three reading frames, we propose a new gene expression paradigm, “ one transcript, three translations ”, which is an amendment to the traditional “ one gene, one/multiple peptides ” hypotheses. Finally, we concluded that the genetic code was optimized for frameshift tolerating in the early evolution, which endows every protein coding gene a character of shiftability , an inherent and everlasting ability to tolerate frameshift mutations, and serves as an innate mechanism for cells to deal with the frameshift problem.