ACCURACY OF PROTEIN-BIOSYNTHESIS - QUASI-SPECIES NATURE OF PROTEINS AND POSSIBILITY OF ERROR CATASTROPHES

Yeast aminoacyl-tRNA synthetases act in a multi-step process when reco gnizing their cognate amino acids; this identification event includes ''physical'' binding and ''chemical'' proof-reading steps. However, th e various enzymes use these single steps at different degrees, and the ir specificities with regard to the 20 naturally occurring amino acids deviate considerably from each other. The characteristic discriminati on factors D were determined for seven synthetases in vitro: the highe st specificity with D values between 28000 and > 500000 were observed with tyrosyl-tRNA synthetase, the lowest values between 130 and 1700 f or lysyl-tRNA synthetase. The tested class I enzymes are more specific than the investigated class II enzymes, and it may be put into discus sion whether this observation can be generalized. Error rates in amino acid recognition differ not only between the individual aminoacyl-tRN A synthetases but also considerably for different amino acids sorted b y the same enzyme. Strikingly, all investigated enzymes exhibit a poor specificity in discrimination of cysteine and tryptophan from their c ognate substrates, and these cases may be regarded as ''specificity ho les'' In view of the observed specificities a protein consisting of 70 0 amino acids would contain maximally up to five ''incorrect'' residue s, if the in vitro error rates are also valid under in vitro condition s. Therefore the terminus ''quasi-species'', an expression which was o riginally created for nucleic acids, is justified. The ''quasi-species '' nature of proteins may become important when genes are translated i n different organisms with different accuracies of the translation app aratus. In such cases different ''quasi-species'' will be obtained. Us ing our data in mathematical models which predict the stability of pro tein synthesizing systems, we find that they are consistent with a sta ble yeast organism which is not prone to die by an ''error catastrophe ''. However, this appears only if average values from our experiments are used for calculations. If a single compound, e.g. the arginine ana log canavanine, is discriminated very poorly from the cognate substrat e, or if the ''specificity holes'' get larger, an ''error catastrophe' ' must be envisaged. (C) 1998 Academic Press.