The genetic code is nearly optimal for allowing additional information within protein-coding sequences
Shalev Itzkovitz1,2 and Uri Alon1,2,3
Author Affiliations
1 Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel;
2 Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot 76100, Israel
Abstract
DNA sequences that code for proteins need to convey, in addition to the protein-coding information, several different signals at the same time. These “parallel codes” include binding sequences for regulatory and structural proteins, signals for splicing, and RNA secondary structure. Here, we show that the universal genetic code can efficiently carry arbitrary parallel codes much better than the vast majority of other possible genetic codes. This property is related to the identity of the stop codons. We find that the ability to support parallel codes is strongly tied to another useful property of the genetic code—minimization of the effects of frame-shift translation errors. Whereas many of the known regulatory codes reside in nontranslated regions of the genome, the present findings suggest that protein-coding regions can readily carry abundant additional information.
The genetic code is the mapping of 64 three-letter codons to 20 amino-acids and a stop signal (Woese 1965; Crick 1968; Knight et al. 2001). The genetic code has been shown to be nonrandom in at least two ways: first, the assignment of amino acids to codons appears to be optimal for minimizing the effect of translational misread errors. This optimality is achieved by mapping close codons (codons that differ by one letter) to either the same amino acids or to chemically related ones (Woese 1965). This feature has been attributed to an adaptive selection of a code, so that errors that misread a codon by one letter would result in minimal effects on the translated protein (Freeland and Hurst 1998; Freeland et al. 2000; Gilis et al. 2001; Wagner 2005b). Second, amino acids with simple chemical structure tend to have more codons assigned to them (Hasegawa and Miyata 1980; Dufton 1997; Di Giulio 2005).
There exist a large number of alternative genetic codes that are equivalent to the real code in these two prominent features (Fig. 1). Here we ask whether the real code stands out among these alternative codes as being optimal for other properties.
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