Theoretical analysis of possible evolutionary trends in the distribution of codons along mRNA

This work is concerned with analysis of the evolutionary features of the distribution of the synonymous codons as part of translated mRNA as following from the commonnest principles of the structure of the translation apparatus. A mathematical model has been developed which depends on: a) translation initiation; b) elongation with an account of isoacceptor tRNA; c) mutual disposition of the codons; d) the distance that the A-sites of two ribosomes cannot get closer than while the translation of an mRNA molecule is in progress; e) sterical blocking of the translation initiation start by the ribosome at the earlier stages of protein synthesis; f) translation termination; g) synthesis and degradation of individual mRNA, tRNA and ribosomes. Because long-running evolutionary processes have been modelled, no regulation of the functioning of the translation apparatus was assumed under the model, nor its interaction with other cellular systems within one cycle of propagation. The dependence of the cell cycle duration, of the rate of incorporation of amino acid residues into the growing polypeptides, of the gross incorporation of amino acids into proteins within one cell cycle, the economical functioning of the translation system, of the averaged elongation rate and of some other functionals on the model parameters has been subject to numerical analysis.

Some inferences can be made from present evidence on the likely trends in the evolution of the codon content of mRNA.

1. There is a long-term tendency to increase the average elongation rate and to improve the economical capability of the translation system in the course of evolution, although locally
2. the parameters may take on lower values.
3. Elevated elongation rates are advantageous for the organism within a wide range of parameter values. The farther away the selection codon from the translation initiation start, the higher the relative value of the acquisition.
4. At a higher translation initiation rate it becomes advantageous for a fixed codon close to the translation start to elongate at a lower rate. The higher the translation initiation rate, the farther away from the initiation start the codon can be.
5. No matter which initial conditions, the general trend in synonymous codon selection is reaching for the state at which "faster" codons are located closer to the end of the translation frame. The more actively translated mRNA, the more it is observed.