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Symmetries of genetic code-doublets.

The fact that 64 base triplets code only about 20 essential amino acids implies a strong degeneracy of certain base doublets. It is shown that the set of degenerate base doublets and the set of non-degenerate base doublets are highlly structured. A mathematical formalism is introduced which allows a systematic description of the consequences of an exchange of bases in a doublet. By this formalism it is shown that the two mentioned set have in fact the same structure.

Biological Evolution

Linear and inverted repetitions in protein sequences.

An extensive search for internal regularities in amino acid sequences has been made, using both the genetic code and the relative frequencies of amino acid alternatives in homologous proteins. The two methods give very similar results and strongly suggest the occurrence of significant linear and inverted repetitions (similar sequences of opposite polarity) in several proteins. A hypothesis is developed to explain the occurrence of such internal regularities in proteins. This hypothesis is based on a process of duplication of an ancestral loop in which a symmetrical arrangement of amino acid allows stabilization by interaction between the amino acid side chains.

Amino Acid Sequence

Application of the 'profiles of relationship' method to distantly related proteins.

An analysis is made of the applicability of the recently published 'profiles of relationship' method for establishing evolutionary relatedness among proteins by using the distantly related proinsulin and neurotoxin protein sequences as a test object. The method is based on a simultaneous group analysis of both the frequency of acceptance of mutations and their genetic code interchangeability. Regularities in the patterns of the profiles, which reflect decreased similarity with the passage of time, are established for typical cases of closely related, distantly related and unrelated proteins. This makes it possible to distinguish distantly related from unrelated proteins without extensive statistical randomization procedures. New evidence is stated in favour of a previously suggested definition of interchangeability which does not consider the third base in the codon. The applicability of the profiles of relationship method is examined on the distant relationship between proinsulin and the snake and scorpion neurotoxins which has been established previously by means of conventional approaches.

Animals

Transfer RNAs for primordial amino acids contain remnants of a primitive code at position 3 to 5.

Analysis of the nucleotide sequence of 1,400 transfer RNAs has revealed the imprint of a prototypic genetic code in position 3-4-5 of the acceptor stem. It appears only in the transfer RNAs for the primordial amino acids ie those found by chemical condensation of a nitrogen-methane-water-ammonia mixture. The model for primitive protein synthesis as mentioned by Crick assumes a direct interaction between the amino acid and a prototypic adaptor oligonucleotide. This has hitherto appeared irreconcilable with the large spatial separation between the aminoacylation site and the anticodon in present day transfer RNAs. The observations reported here show how this paradox can be resolved by a process of duplication and cleavage of a prototypic adaptor.

Amino Acid Sequence

Informational parameters of nucleic acid and molecular evolution.

From the point of view of information theory, a statistical analysis of 2000 nucleic acid sequences (732 coding regions and 1177 non-coding regions) is given. The sequences are grouped into 20 categories. The probability-order-difference (POD) matrix is defined which is used to analyse the evolutionary distance of any two categories of sequences. The informational parameters D1, D2 and X = (1 + D1/D2)-1 and F are calculated for each sequence and averaged in each category. The statistical dependence of these parameters on molecular evolution is discussed. It is found that [X] is a good statistical quantity which describes the vocabulary compositions as well as the grammatical constructions of the genetic language. From the statistical analysis it is shown that [X] may play an important role in investigating the evolutionary level of nucleic acid molecules.

Base Sequence

[The meaning of the genetic code: reconstruction of the stage of prebiologic evolution].

According to a certain order in sets of the two first codon bases, 20 common amino acids can be divided into 5 families each containing 4 amino acids; the corresponding order in the distribution of codon bases can be easily detected, if common amino acids are distributed for the numbers of hydrogen atoms per molecule (Sukhodolets, 1980). In the present paper, the order in the distribution of codon bases is explained on the basis of the hypothesis claiming the prebiological existence of crystalline associates composed of amino acids and bases as free molecules. In these heterogeneous crystalline associates amino acids were analogs to the base douplets and the arrangement of molecules followed a certain rule, namely: 40 protons per molecular complex forming a standard structural compartment. It is proposed that the crystalline associates existed as lyotropic liquid crystals with hydrocarbons as solvent. The genetical code allows to discover two different original crystallization types for bases and amino acids. Therefore, the life possibly originates from combining in the same structure different crystallization patterns, which resulted in formation of a finite crystalline associate.

Amino Acid Sequence

Inadequacy of prebiotic synthesis as origin of proteinous amino acids.

The production of some nonproteinous, and lack of production of other proteinous, amino acids in model prebiotic synthesis, along with the instability of glutamine and asparagine, suggest that not all of the 20 present day proteinous amino acids gained entry into proteins directly from the primordial soup. Instead, a process of active co-evolution of the genetic code and its constituent amino acids would have to precede the final selection of these proteinous amono acids.

Amino Acids

Evaluation of compositional nonrandomness in proteins.

Cornish-Bowden and Marson have recently suggested that the finite sampling component of Q, a measure of nonrandomness in the amino acid composition of proteins, may have been underestimated because it was calculated on the basis of the genetic code table frequencies rather than on the basis of the average natural abundance with which the twenty amino acids actually occur in proteins. This underestimate would lead to an overestimate of Qc a measure of selective effects above and beyond those imposed by the average natural abundance of the amino acids. In this paper the finite sampling component of Q is quantitatively estimated on the basis of these natural abundances and found to reduce Qc from its previous average value of 24.3 to the lower value of 9.7, with the standard deviation of the population of Qc values being 12.5. Individual Qc values are given for 81 protein families of mean composition per 61 codons of Ala5.3Arg2.4Asn3.0Asp3.6Cys1.5Gln2.6Glu3.5Gly4.7His1.3Ile3.4Leu4.5Lys4.2Met1.0Phe2.3Pro2.3Ser4.2Thr3.6Trp0.8Tyr2.6Val4.2. The mean Qc value of 9.7 is notably small, and indicates that quantitatively minimal adjustments away from the average protein composition are necessary to maintain many different biological functions. This small value, however, is shown to differ significantly from the value of zero expected were the natural abundances of the amino acids the only selective constraint. These small deviations from the natural abundances are thus effectively selected for in the Darwinian sense.

Amino Acid Sequence

Atavistic mutations reflect the long life span of dispensable genes.

Most of the major innovations in evolution occurred at the very beginning of life on this earth some 3.5 billion years ago before the division of eukaryotes from prokaryotes. This initial innovativeness was due, in no small part, to the peculiar construction of primordial coding sequences that were repeats of base oligomers, the number of bases in oligomeric units not being a multiple of three. Such coding sequences are conferred with a measure of immortality. Because of this initial immortality and of long life span of genes after becoming dispensable, the ancient gene may remain silenced in particular phylogenetic trees for a very long time, only to be resurrected later. Hemoglobin genes expressed in exceptional bacteria, plants, worms, insects, as well as in all vertebrates are a good example of this. Atavistic mutations are more dramatic visible examples of such resurrection of long dormant genes. A few interesting examples are given.

Animals

Evolution from primordial oligomeric repeats to modern coding sequences.

It seems as though nature was most innovative at the very beginning of life on this Earth a few billion years ago. For example, the functional competence of most, if not all, of the sugar-metabolizing enzymes was clearly established before the division of eukaryotes from prokaryotes eons ago, each critical active-site amino acid sequence being conserved ever since by bacteria as well as by mammals. I contend that this initial innovativeness was due to the first set of coding sequences being repeats of base oligomers, thus encoding polypeptide chains of various periodicities; such periodical polypeptide chains can easily acquire alpha-helical and beta-sheet-forming segments. In fact, the entire length of sugar-metabolizing enzymes is comprised of alternating alpha-helical and beta-sheet-forming segments. In the prebiotic (therefore nonenzymatic) replication of nucleic acids, what was in short supply was long templates, for there apparently was no inherent obstacle in copying of long templates, if such existed, in the presence of Zn2+. I submit that in this prebiotic condition, only those nucleotide oligomers that were internal doubles were automatically assured of progressive elongation to become long templates. For example, a decamer that was a pentameric repeat and its complementary sequence may pair unequally to initiate the next round of replication: first unit pairing with second, and a paired segment serving as a primer. As a consequence of this unequal pairing, decameric templates managed to become pentadecameric templates only after one round of replication, and this elongation process had no inherent limit.

Amino Acid Sequence

Genetic code redundancy and its differential influence on the evolution of protein interiors versus exteriors.

The distinctive amino acid compositions of protein exteriors and interiors were compared to the composition bias imposed by genetic code redundancy. It transpired that the synonym allocation is biased more in favour of those residues which are preferred in interiors, and this leads to an average interior residue being more probable and less mutable compared to an exterior residue. The general implications for protein evolution are discussed in association with the known evolutionary behavior of particular protein families. It is suggested that some proteins may have their structural history "fossilised" in their interiors and that the "amino acid" code is in reality a "protein" code.

Amino Acid Sequence