Abstract
BackgroundThe (almost) universality of the genetic code is one of the most intriguing properties of cellular life. Nevertheless, several variants of the standard genetic code have been observed, which differ in one or several of 64 codon assignments and occur mainly in mitochondrial genomes and in nuclear genomes of some bacterial and eukaryotic parasites. These variants are usually considered to be the result of non-adaptive evolution. It has been shown that the standard genetic code is preferential to randomly assembled codes for its ability to reduce the effects of errors in protein translation.ResultsUsing a genotype-to-phenotype mapping based on a quantitative model of protein folding, we compare the standard genetic code to seven of its naturally occurring variants with respect to the fitness loss associated to mistranslation and mutation. These fitness losses are computed through computer simulations of protein evolution with mutations that are either neutral or lethal, and different mutation biases, which influence the balance between unfolding and misfolding stability. We show that the alternative codes may produce significantly different mutation and translation loads, particularly for genomes evolving with a rather large mutation bias. Most of the alternative genetic codes are found to be disadvantageous to the standard code, in agreement with the view that the change of genetic code is a mutationally driven event. Nevertheless, one of the studied alternative genetic codes is predicted to be preferable to the standard code for a broad range of mutation biases.ConclusionsOur results show that, with one exception, the standard genetic code is generally better able to reduce the translation load than the naturally occurring variants studied here. Besides this exception, some of the other alternative genetic codes are predicted to be better adapted for extreme mutation biases. Hence, the fixation of alternative genetic codes might be a neutral or nearly-neutral event in the majority of the cases, but adaptation cannot be excluded for some of the studied cases.
Highlights
The universality of the genetic code is one of the most intriguing properties of cellular life
The second scenario takes place if one codon disappears from a given genome. This is likely in small genomes with large guanine/cytosine (GC) or adenine/thymine (AT) content, as it is the case for many mitochondrial genomes and nuclear genomes of parasitic microbes
The protein structure is assumed to have been already optimized by natural selection and is kept fixed throughout evolution, as represented by the experimental structure found in the Protein Data Bank (PDB)
Summary
The (almost) universality of the genetic code is one of the most intriguing properties of cellular life. In this case the translation system may change without any cost, and the codon may be 'conquered' by another amino acid Both scenarios consider that alternative genetic codes are the result of non-adaptive or neutral evolution, even though 'genomic streamlining' (i.e., selective pressure to minimize the genome by eliminating a tRNA) has been proposed as a possible advantage of code changes [25,26]. It has not been addressed whether these variants differ from the standard genetic code as far as mutation and translation loads are concerned
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