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PubMed2001

The origin of the genetic code cannot be studied using measurements based on the PAM matrix because this matrix reflects the code itself, making any such analyses tautologous.

Freeland et al. (Mol. Biol. Evol. 2000 a, 17, 511--518) have recently used a transformation of the PAM 74-100 matrix to study the level of optimization reached during genetic code origin. Since the PAM matrix counts the amino acid substitutions that occurred in families of homologous proteins during molecular evolution and as this process is mediated by the genetic code structure itself, it could be that the influence of the code on this matrix is such as to make any conclusion insignificant. As will be shown in the present paper, the transformation of the PAM matrix is affected in a non-marginal way by the organization of the genetic code and, thus, renders the analysis of Freeland et al. tautologous. Although, under the hypothesis of a highly optimized genetic code, some correlations may be expected between a measurement of similarity between amino acids and the genetic code structure, no certain conclusions can be drawn for the measurement used by Freeland et al.

Amino Acid Sequence↗
PubMed1983

A prevalent persistent global nonrandomness that distinguishes coding and non-coding eucaryotic nuclear DNA sequences.

Coding sequences of eucaryotic nuclear DNA were characterized by an excess of short runs and a deficit of long runs of weak and of strong hydrogen bounding bases; non-coding sequences by a deficit of short runs and an excess of long runs, in the same of purines and of pyrimidines. The conservation of these attributes across DNA sequences coding for proteins of widely different function, across widely different eucaryotic species for the same protein and across related genes that diverged a long time ago and that now show large differences in base and, if coding, amino acid sequence suggested that these attributes have survival value. It was concluded that these attributes constitute probalistic constraints on the primary structure (base sequence) of both coding and non-coding DNA.

Animals↗
PubMed1993

Neutral adaptation of the genetic code to double-strand coding.

We lay new foundations to the hypothesis that the genetic code is adapted to evolutionary retention of information in the antisense strands of natural DNA/RNA sequences. In particular, we show that the genetic code exhibits, beyond the neutral replacement patterns of amino acid substitutions, optimal properties by favoring simultaneous evolution of proteins encoded in DNA/RNA sense-antisense strands. This is borne out in the sense-antisense transformations of the codons of every amino acid which target amino acids physicochemically similar to each other. Moreover, silent mutations in the sense strand generate conservative ones in its antisense counterpart and vice versa. Coevolution of proteins coded by complementary strands is shown to be a definite possibility, a result which does not depend on any physical interaction between the coevolving proteins. Likewise, the degree to which the present genetic code is dedicated to evolutionary sense-antisense tolerance is demonstrated by comparison with many randomized codes. Double-strand coding is quantified from an information-theoretical point of view.

Adaptation, Biological↗
PubMed2005

Error minimization and coding triplet/binding site associations are independent features of the canonical genetic code.

The canonical genetic code has been reported both to be error minimizing and to show stereochemical associations between coding triplets and binding sites. In order to test whether these two properties are unexpectedly overlapping, we generated 200,000 randomized genetic codes using each of five randomization schemes, with and without randomization of stop codons. Comparison of the code error (difference in polar requirement for single-nucleotide codon interchanges) with the coding triplet concentrations in RNA binding sites for eight amino acids shows that these properties are independent and uncorrelated. Thus, one is not the result of the other, and error minimization and triplet associations probably arose independently during the history of the genetic code. We explicitly show that prior fixation of a stereochemical core is consistent with an effective later minimization of error.

Base Sequence↗
PubMed2005

Comparative analysis of the Code of Professional Ethics in Bulgaria and the Hippocratic Oath, Declaration of Geneva and International Code of Medical Ethics.

In this paper I aim at making a comparative analysis of The Code of Professional Ethics in Bulgaria (CPEB), The Hippocratic Oath, The Declaration of Geneva, and The World Medical Association International Code of Medical Ethics. Two problems of special interest are explored: whether the leading principles of fundamental ethical codes are presented in CPEB and whether the code itself is relevant to the current medical professional and social situation in the country. The conclusion reached after a step-by-step analysis is that CPEB attempts to cover a wide range of principles and problems in medical practice and corresponds with the fundamental ethical codes. Although the code is criticized in some points, it could be very useful, provided that it is well publicized in the profession.

Bulgaria↗
PubMed1983

[The genetic code and cyclic codes].

The genetic code can be considered as degenerated from a minimal cyclic code, whose maximal chain is given. We study the relation of this code with the cyclic code corresponding to the 64 triplets. Finally we compare the minimal code to that obtained from a binary cyclic code.

Adenine↗
PubMed1984

Analysis of mRNA coding for blood-stage antigens of a rodent malarial parasite, Plasmodium yoelii: mRNA coding for a possible protective antigen purify as poly A-.

We have analyzed mRNA coding for blood-stage antigens of Plasmodium yoelii by using cellfree translation of poly A+ and poly A- RNA in conjunction with immunoprecipitations. Most of the antigens recognized by mouse hyperimmune serum to P. yoelii were coded by poly A+ mRNA ranging in size from 15S to 28S. However, certain P. yoelii antigens, notably those with m.w. greater than 150 kilodaltons (kd), were coded by mRNA that purified as being poly A-. Antigens recognized by a protective monoclonal antibody (McAb) were coded by such operationally poly A- RNA. Three polypeptides apparently coded by different poly A- RNA were immunoprecipitated by this McAb. With the use of another McAb, a poly A+ mRNA of about 19S was identified as coding for a polypeptide of 46 kd synthesized in cellfree translation reactions. The same McAb recognized a 34 kd polypeptide in metabolically labeled polypeptides of P. yoelii. This antigen appeared to be processed in vivo but not in vitro. The observation that some mRNA of P. yoelii purify as being poly A- has significant implications for the construction of cDNA libraries that employ poly A+ mRNA of malarial parasites: if it applies to other species of plasmodia, some potentially important operationally poly A- mRNA may not be represented in such libraries.

Animals↗
PubMedDate not supplied

Comorbidities, complications, and coding bias. Does the number of diagnosis codes matter in predicting in-hospital mortality?

OBJECTIVE: Incomplete coding of secondary diagnoses may bias assessments of patient risks of poor outcomes using administrative health care databases, most of which allow only five diagnoses. The Medicare program is expanding the number of possible diagnoses from five to nine, aiming to improve coding completeness. We examined the impact of having more diagnosis codes available on assessments of risk of death. DESIGN: We used 1988 computerized hospital discharge abstract data from California, which allow up to 25 diagnoses per discharge, to select a sample of hospitalized patients and assessed the relationship between the presence of 29 specific secondary diagnoses and the risk of in-hospital death. SETTING: Nonfederal acute-care hospitals in California. STUDY POPULATION: All patients at least 65 years of age who were hospitalized for stroke, pneumonia, acute myocardial infarction, or congestive heart failure in California in 1988 (N = 162,790). MAIN OUTCOME MEASURES: Relative risk of death for each specific secondary diagnosis. RESULTS: Many conditions that on a clinical basis would be expected to increase the risk of death, such as adult-onset diabetes mellitus, previous myocardial infarction, angina, and ventricular premature beats, were associated with a lower risk of in-hospital death. CONCLUSIONS: Bias against coding of chronic or comorbid conditions on the computerized discharge abstracts of patients who die best explains these results. Efforts to improve diagnosis coding completeness solely by increasing the number of available coding spaces may not succeed.

Aged↗
PubMed1997

The "clustered structure" of the purines/pyrimidines distribution in DNA distinguishes systematically between coding and non-coding sequences.

A method allowing to measure the inhomogeneous distribution of purines/pyrimidines in nucleotide sequences is developed. We show that this measure relates to the coding or non-coding character of the considered sequence. Coding sequences present a near to the random Pu or Py distribution. This property is shared by both protein-coding DNA and functional RNA-coding DNA. Non-coding sequences present a highly clustered inhomogeneity. We propose the hypothesis, corroborated with appropriate computer simulations, that this is due to the action of various transposition events accumulated for long time periods.

Animals↗
PubMed2006

An analytical model of gene evolution with 9 mutation parameters: an application to the amino acids coded by the common circular code.

We develop here an analytical evolutionary model based on a trinucleotide mutation matrix 64 x 64 with nine substitution parameters associated with the three types of substitutions in the three trinucleotide sites. It generalizes the previous models based on the nucleotide mutation matrices 4 x 4 and the trinucleotide mutation matrix 64 x 64 with three and six parameters. It determines at some time t the exact occurrence probabilities of trinucleotides mutating randomly according to these nine substitution parameters. An application of this model allows an evolutionary study of the common circular code [Formula: see text] of eukaryotes and prokaryotes and its 12 coded amino acids. The main property of this code [Formula: see text] is the retrieval of the reading frames in genes, both locally, i.e. anywhere in genes and in particular without a start codon, and automatically with a window of a few nucleotides. However, since its identification in 1996, amino acid information coded by [Formula: see text] has never been studied. Very unexpectedly, this evolutionary model demonstrates that random substitutions in this code [Formula: see text] and with particular values for the nine substitutions parameters retrieve after a certain time of evolution a frequency distribution of these 12 amino acids very close to the one coded by the actual genes.

Amino Acids↗
PubMedDate not supplied

Role of statistical symmetries in sensory coding: an optimal scale invariant code for vision.

The visual system is the most studied sensory pathway, which is partly because visual stimuli have rather intuitive properties. There are reasons to think that the underlying principle ruling coding, however, is the same for vision and any other type of sensory signal, namely the code has to satisfy some notion of optimality--understood as minimum redundancy or as maximum transmitted information. Given the huge variability of natural stimuli, it would seem that attaining an optimal code is almost impossible; however, regularities and symmetries in the stimuli can be used to simplify the task: symmetries allow predicting one part of a stimulus from another, that is, they imply a structured type of redundancy. Optimal coding can only be achieved once the intrinsic symmetries of natural scenes are understood and used to the best performance of the neural encoder. In this paper, we review the concepts of optimal coding and discuss the known redundancies and symmetries that visual scenes have. We discuss in depth the only approach which implements the three of them known so far: translational invariance, scale invariance and multiscaling. Not surprisingly, the resulting code possesses features observed in real visual systems in mammals.

Animals↗