An information theory of the genetic code

An information theory of the genetic code is given, which deals with the process by which template codes (nucleotides or codons) choose substrate codes (nucleotides or anti-codons) in accordance with the base-pairing rules in the chain elongation phase of polynucleotide or polypeptide synthesis. A definite period of recognition time (τ) required for a template code to discriminate a substrate code is proposed, and an experimental method for determining the time is suggested. A substrate word is defined to be the sequence of substrate codes which have appeared at a recognition site in turn before a substrate code complementary to a template code first appears, and the mean length of substrate words (F) is derived from the mole fractions of template codes and substrate codes. The chain elongation rate is greatest when the mole fractions of template codes is proportional to the square of those of substrate codes to minimize the mean recognition time per word (Fτ). The uncertainty of a template (G) and the uncertainty of a medium (M) respectively are derived from the minimum of the function F. The amount of genetic information contained in a template is measured by the function G. The unit of the amount of genetic information is termed “cit”. The function M, the ratio of the number of all binary collisions to the number of homogeneous binary collisions in a mixture of different molecules, may be the new other “entropy” which represents informational properties of the mixture not represented by thermodynamic entropy of mixing. Both functions (G and M) have maxima when all random variables are equal and they are multiplicative in nature in contrast to entropy which is additive. The multiplicativity of the function G may contribute to the enormous informational capacity of genes.     

On the information content of the genetic code

In living organisms 20 amino acids along with the terminator value(s) are encoded by 64 codons giving a degeneracy of the codons as described by the genetic code. A basic theoretical problem of genetic codes is to explain the particular distribution of degeneracies of partitions involved in the codes. In this work the degeneracy problem is considered in the framework of information theory. It is shown by direct numerical evaluation of a certain degeneracy information function associated with the genetic code that the degeneracy of the codes is observed to be related to the optimization of this function.     

A genetic code Boolean structure. II. The genetic information system as a Boolean information system

A Boolean structure of the genetic code where Boolean deductions have biological and physicochemical meanings was discussed in a previous paper. Now, from these Boolean deductions we propose to define the value of amino acid information in order to consider the genetic information system as a communication system and to introduce the semantic content of information ignored by the conventional information theory. In this proposal, the value of amino acid information is proportional to the molecular weight of amino acids with a proportional constant of about 1.96×10²⁵ bits per kg. In addition to this, for the experimental estimations of the minimum energy dissipation in genetic logic operations, we present two postulates: (1) the energy E _i (i = 1, 2, ..., 20) of amino acids in the messages conveyed by proteins is proportional to the value of information, and (2) amino acids are distributed according to their energy E _i so the amino acid population in proteins follows a Boltzmann distribution. Specifically, in the genetic message carried by the DNA from the genomes of living organisms, we found that the minimum energy dissipation in genetic logic operations was close to kTLn(2) joules per bit.     

Different types of secondary information in the genetic code

Whole-genome and functional analyses suggest a wealth of secondary or auxiliary genetic information (AGI) within the redundancy component of the genetic code. Although there are multiple aspects of biased codon use, we focus on two types of auxiliary information: codon-specific translational pauses that can be used by particular proteins toward their unique folding and biased codon patterns shared by groups of functionally related mRNAs with coordinate regulation. AGI is important to genetics in general and to human disease; here, we consider influences of its three major components, biased codon use itself, variations in the tRNAome, and anticodon modifications that distinguish synonymous decoding. AGI is plastic and can be used by different species to different extents, with tissue-specificity and in stress responses. Because AGI is species-specific, it is important to consider codon-sensitive experiments when using heterologous systems; for this we focus on the tRNA anticodon loop modification enzyme, CDKAL1, and its link to type 2 diabetes. Newly uncovered tRNAome variability among humans suggests roles in penetrance and as a genetic modifier and disease modifier. Development of experimental and bioinformatics methods are needed to uncover additional means of auxiliary genetic information.     

Simulated evolution applied to study the genetic code optimality using a model of codon reassignments

Background  

As the canonical code is not universal, different theories about its origin and organization have appeared. The optimization or level of adaptation of the canonical genetic code was measured taking into account the harmful consequences resulting from point mutations leading to the replacement of one amino acid for another. There are two basic theories to measure the level of optimization: the statistical approach, which compares the canonical genetic code with many randomly generated alternative ones, and the engineering approach, which compares the canonical code with the best possible alternative.     

A harmonic structure of the genetic code

In this paper is presented a new, very harmonic structure of the genetic code (GC) within a system of "4 x 5" (and/or of "5 x 4") of amino acids (AAs) in two variants. In first variant, the five rows within the system start with one polar charged amino acid (AA) each, making first column, consisting from five polar charged AAs (D, R, K, H, E). Five polar non-charged AAs (N, P, Y, W, Q) follow, then five non-polar AAs as last column (A, L, F, V, I) and, finally, five polar or non-polar AAs, in a combination, as first to last column (A as non-polar; S, T as polar, and G, P as ambivalent AAs). A second variant is subsequent to this one-"4 x 5" system with five nitrogen AAs (K, R, P, H, W), five oxygen (D, E, Y, S, T), five solely carbon (A, L, F, V, I) and five "combined" AAs (G with hydrogen as side chain; C and M with carbon and sulfur; N and Q with carbon, oxygen and nitrogen). A strict balance of atom and nucleon number as well as molecule mass follows the classification in both system variants.     

A content-centric organization of the genetic code

The codon table for the canonical genetic code can be rearranged in such a way that the code is divided into four quarters and two halves according to the variability of their GC and purine contents, respectively. For prokaryotic genomes, when the genomic GC content increases, their amino acid contents tend to be restricted to the GC-rich quarter and the purine-content insensitive half, where all codons are fourfold degenerate and relatively mutation-tolerant. Conversely, when the genomic GC content decreases, most of the codons retract to the AUrich quarter and the purine-content sensitive half; most of the codons not only remain encoding physicochemically diversified amino acids but also vary when transversion （between purine and pyrimidine） happens. Amino acids with sixfolddegenerate codons are distributed into all four quarters and across the two halves; their fourfold-degenerate codons are all partitioned into the purine-insensitive half in favorite of robustness against mutations. The features manifested in the rearranged codon table explain most of the intrinsic relationship between protein coding sequences （the informational content） and amino acid compositions （the functional content）. The renovated codon table is useful in predicting abundant amino acids and positioning the amino acids with related or distinct physicochemical properties.     

A change in the genetic code inMycoplasma capricolum

Summary Mycoplasma capricolum was previously found to use UGA instead of UGG as its codon for tryptophan and to contain 75%A+ T in its DNA. The codon change could have been due to mutational pressure to replace C+G by A+T, resulting in the replacement of UGA stop codons by UAA, change of the anticodon in tryptophan tRNA from CCA to UCA, and replacement of UGG tryptophan codons by UGA. None of these changes should have been deleterious.     

A search for symmetries in the genetic code

A search for symmetrics based on the classification theorem of Cartan for the compact simple Lie algebras is performed to verify to what extent the genetic code is a manifestation of some underlying symmetry. An exact continuous symmetry group can not be found to reproduce the present, universal code. However a unique approximate symmetry group is compatible with codon assignment for the fundamental amino acids and the termination codon. In order to obtain the actual genetic code, the symmetry must be slightly broken.     

Adding pyrrolysine to the Escherichia coli genetic code

Pyrrolysyl-tRNA synthetase and its cognate suppressor tRNA(Pyl) mediate pyrrolysine (Pyl) insertion at in frame UAG codons. The presence of an RNA hairpin structure named Pyl insertion structure (PYLIS) downstream of the suppression site has been shown to stimulate the insertion of Pyl in archaea. We study here the impact of the presence of PYLIS on the level of Pyl and the Pyl analog N-epsilon-cyclopentyloxycarbonyl-l-lysine (Cyc) incorporation using a quantitative lacZ-luc tandem reporter system in an Escherichia coli context. We show that PYLIS has no effect on the level of neither Pyl nor Cyc incorporation. Exogenously supplying our reporter system with d-ornithine significantly increases suppression efficiency, indicating that d-ornithine is a direct precursor to Pyl.