Evolution of the genetic code: the nonsense, antisense, and antinonsense codes make no sense

According to the molecular recognition theory, the complementarity of the s ense and nonsense DNA strands is reflected in a complementarity of polypept ides and the corresponding nonsense polypeptides. A comparison of the sense and nonsense code matrices, and of the antisense and antinonsense code mat rices, either by visual inspection or by comparing the corresponding hydrop hobicity matrices (e.g. by simply adding them together), revealed no comple mentarity of these pairs of matrices in terms of possible attractive physic al forces. Instead, it was evident that the codes divide the amino acids in to two major groups: hydrophilic and hydrophobic, a division which is direc tly correlated with the folding property of proteins. A simple primordial g enetic code distinguishing between these two types of amino acids would hav e been capable of generating three-dimensionally folded peptides, which cou ld stabilize coding RNAs by forming ribonucleoprotein complexes. This evolu tionary scheme is reflected in the present organisation of information proc essing and storage in essentially all organisms. RNAs are processed and tra nslated into proteins by ribonucleoproteins, while other steps in informati on retrieval and processing, such as DNA replication, transcription, protei n folding and posttranslational processing, are catalyzed by proteins. This shows that the evolution of DNA as an information storage medium was a sec ondary event, unrelated to the evolution of the genetic code. From the prim ordial hydrophilic/hydrophobic (f.ex. Leu/Arg) code, evolution proceeded by introduction of a catalytic amino acid (Ser). The further evolution of the code has mainly served to increase the number of functional hydrophilic am ino acids, since there has not been a great advantage in increasing the num ber of structural, hydrophobic amino acids. At some stage during the evolut ion of the genetic code, double-stranded DNA was introduced as a maximally safe genetic copy of RNA. This required the action of highly specific enzym es, and was therefore preceded by the refinement of the genetic code. As a conclusion of this evolutionary scheme, it can be inferred that, in general only the sense strand encodes proteins. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.