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[Characteristics of nucleotide blocks in coding and non-coding DNA sequences from different organisms].

A statistical analysis of occurrence of particular nucleotide runs (1 divided by 10 nucleotides long) in DNA sequences of different species has been carried out. There are considerable differences in run distributions in DNA sequences of prokaryotes, invertebrates and vertebrates. Distribution of various types of runs has been found to be different in coding and non-coding sequences. There is an abundance of short runs 1 divided by 2 nucleotides long in coding sequences, and there is a deficiency of such runs in the non-coding regions. However, some interesting exceptions from this rule exist: for run distribution of adenine in prokaryotes and for distribution of purine-pyrimidine runs in eukaryotes. This may be stipulated by the fact that the distribution of runs are predetermined by structural peculiarities of the entire DNA molecule. Runs of guanine or cytosine of three to six nucleotides long occur predominantly in the non-coding DNA regions in eukaryotes, especially in vertebrates.

Animals↗

An evolutionary analytical model of a complementary circular code simulating the protein coding genes, the 5' and 3' regions.

The self-complementary subset T0 = X0 [symbol: see text] ¿AAA, TTT¿ with X0 = ¿AAC, AAT, ACC, ATC, ATT, CAG, CTC, CTG, GAA, GAC, GAG, GAT, GCC, GGC, GGT, GTA, GTC, GTT, TAC, TTC¿ of 22 trinucleotides has a preferential occurrence in the frame 0 (reading frame established by the ATG start trinucleotide) of protein (coding) genes of both prokaryotes and eukaryotes. The subsets T1 = X1 [symbol: see text] ¿CCC¿ and T2 = X2 [symbol: see text] ¿GGG¿ of 21 trinucleotides have a preferential occurrence in the shifted frames 1 and 2 respectively (frame 0 shifted by one and two nucleotides respectively in the 5'-3' direction). T1 and T2 are complementary to each other. The subset T0 contains the subset X0 which has the rarity property (6 x 10(-8) to be a complementary maximal circular code with two permutated maximal circular codes X1 and X2 in the frames 1 and 2 respectively. X0 is called a C3 code. A quantitative study of these three subsets T0, T1, T2 in the three frames 0, 1, 2 of protein genes, and the 5' and 3' regions of eukaryotes, shows that their occurrence frequencies are constant functions of the trinucleotide positions in the sequences. The frequencies of T0, T1, T2 in the frame 0 of protein genes are 49, 28.5 and 22.5% respectively. In contrast, the frequencies of T0, T1, T2 in the 5' and 3' regions of eukaryotes, are independent of the frame. Indeed, the frequency of T0 in the three frames of 5' (respectively 3') regions is equal to 35.5% (respectively 38%) and is greater than the frequencies T1 and T2, both equal to 32.25% (respectively 31%) in the three frames. Several frequency asymmetries unexpectedly observed (e.g. the frequency difference between T1 and T2 in the frame 0), are related to a new property of the subset T0 involving substitutions. An evolutionary analytical model at three parameters (p, q, t) based on an independent mixing of the 22 codons (trinucleotides in frame 0) of T0 with equiprobability (1/22) followed by t approximately 4 substitutions per codon according to the proportions p approximately 0.1, q approximately 0.1 and r = 1 - p - q approximately 0.8 in the three codon sites respectively, retrieves the frequencies of T0, T1, T2 observed in the three frames of protein genes and explains these asymmetries. Furthermore, the same model (0.1, 0.1, t) after t approximately 22 substitutions per codon, retrieves the statistical properties observed in the three frames of the 5' and 3' regions. The complex behaviour of these analytical curves is totally unexpected and a priori difficult to imagine.

Animals↗

Origins of gene, genetic code, protein and life: comprehensive view of life systems from a GNC-SNS primitive genetic code hypothesis.

We have investigated the origin of genes, the genetic code, proteins and life using six indices (hydropathy, alpha-helix, beta-sheet and beta-turn formabilities, acidic amino acid content and basic amino acid content) necessary for appropriate three-dimensional structure formation of globular proteins. From the analysis of microbial genes, we have concluded that newly-born genes are products of nonstop frames (NSF) on antisense strands of microbial GC-rich genes [GC-NSF(a)] and from SNS repeating sequences [(SNS)n] similar to the GC-NSF(a) (S and N mean G or C and either of four bases, respectively). We have also proposed that the universal genetic code used by most organisms on the earth presently could be derived from a GNC-SNS primitive genetic code. We have further presented the [GADV]-protein world hypothesis of the origin of life as well as a hypothesis of protein production, suggesting that proteins were originally produced by random peptide formation of amino acids restricted in specific amino acid compositions termed as GNC-, SNS- and GC-NSF(a)-0th order structures of proteins. The [GADV]-protein world hypothesis is primarily derived from the GNC-primitive genetic code hypothesis. It is also expected that basic properties of extant genes and proteins could be revealed by considerations based on the scenario with four stages.

Amino Acids↗

A group theory analysis of the ambiguities in the genetic code: on the existence of a generalized genetic code.

It is known that in the transcription of genetic information there are ambiguities, i.e. the fact that a triplet codes for several aminoacids. This has generally been taken as due to errors in the transcription mechanisms. However, it has been postulated that instead of accidental miscoding, ambiguities are part of the expression of a generalized genetic code which depends on biological context. Group theory has been used to find the generalized genetic code. Here we present a new group theory approach which we think removes some weaknesses of previous works. The generalized genetic code presented here is different from that previously reported. We compare our results with experimental evidence and discuss the predictions presented.

Amino Acids↗

Identification of protein coding genes in genomes with statistical functions based on the circular code.

A new statistical approach using functions based on the circular code classifies correctly more than 93% of bases in protein (coding) genes and non-coding genes of human sequences. Based on this statistical study, a research software called 'Analysis of Coding Genes' (ACG) has been developed for identifying protein genes in the genomes and for determining their frame. Furthermore, the software ACG also allows an evaluation of the length of protein genes, their position in the genome, their relative position between themselves, and the prediction of internal frames in protein genes.

Base Sequence↗

An operational RNA code for amino acids and possible relationship to genetic code.

RNA helical oligonucleotides that recapitulate the acceptor stems of transfer RNAs, and that are devoid of the anticodon trinucleotides of the genetic code, are aminoacylated by aminoacyl tRNA synthetases. The specificity of aminoacylation is sequence dependent, and both specificity and efficiency are generally determined by only a few nucleotides proximal to the amino acid attachment site. This sequence/structure-dependent aminoacylation of RNA oligonucleotides constitutes an operational RNA code for amino acids. To a rough approximation, members of the two different classes of tRNA synthetases are, like tRNAs, organized into two major domains. The class-defining conserved domain containing the active site incorporates determinants for recognition of RNA mini-helix substrates. This domain may reflect the primordial synthetase, which was needed for expression of the operational RNA code. The second synthetase domain, which generally is less or not conserved, provides for interactions with the second domain of tRNA, which incorporates the anticodon. The emergence of the genetic from the operational RNA code could occur when the second domain of synthetases was added with the anticodon-containing domain of tRNAs.

Amino Acid Sequence↗

Coding coenzyme handles: a hypothesis for the origin of the genetic code.

The coding coenzyme handle hypothesis suggests that useful coding preceded translation. Early adapters, the ancestors of present-day anticodons, were charged with amino acids acting as coenzymes of ribozymes in a metabolically complex RNA world. The ancestral aminoacyl-adapter synthetases could have been similar to present-day self-splicing tRNA introns. A codon-anticodon-discriminator base complex embedded in these synthetases could have played an important role in amino acid recognition. Extension of the genetic code proceeded through the take-over of nonsense codons by novel amino acids, related to already coded ones either through precursor-product relationship or physicochemical similarity. The hypothesis is open for experimental tests.

Amino Acyl-tRNA Synthetases↗

Cracking the code: the genesis, use and future of the Code of Conduct.

This paper reflects on the genesis of the Code of Conduct for the International Red Cross and Red Crescent Movement and Non-Governmental Organizations (NGOs) in Disaster Relief, on the tenth anniversary of its adoption. The origins, usage and future of the code are examined with respect to three debates, current at the time of its inception, namely: the debate about the core content of humanitarianism; the debate about coherence and the consensual nature of the humanitarian community; and the debate about the need for, and the ability to demonstrate, accountability. The paper concludes that although the Code of Conduct was very much a product of its time, its content remains relevant today. However, its future application hinges on the capacity of those who purport to follow it to realise true accountability, and on proving that the code, written essentially for natural disasters, is relevant to contemporary complex emergencies.

Altruism↗

Protamines, histones and the genetic code. New evidence for code evaluations.

A new approach is presented to give evidence for the theories of Jukes and Crick (1-3) that at a more primitive stage the genetic code consisted of doublets separated by "comma-bases" rather than true triplets and that G and C or A and U are the exclusive bases used by the primordial code. This approach makes use of the conservation of the histone IV sequence over extremely long periods of time by comparing the amino acid composition of the average vertebrate protein with the one of histone IV, a reconstructed ancestral polypeptide and various nuclear proteins, homologous or otherwise related to it. All protamines studied and the majority of histones show deviations from the average vertebrate protein which are statistically highly significant if the amino acids sufficiently coded for by the first two bases are compared. A similar result is obtained for those amino acids which are sufficiently coded for by the first two bases of the codon and have codons composed of G and C only.

Amino Acid Sequence↗

The chromatin regulatory code: beyond a histone code.

In this commentary on the contribution by Arndt Benecke in this issue, I discuss why the notion of "chromatin code" introduced and elaborated in this paper is to be preferred to that of "histone code". Speaking of a code as regards nucleosome conformation and histone tail post-translational modifications only makes sense within the chromatin fiber, where their physico-chemical features can be translated into regulatory programs at the genome level, by means of a complex, multi-level interplay with the fiber architecture and dynamics settled in the course of Evolution. In particular, this chromatin code presumably exploits allosteric transitions of the chromatin fiber. The chromatin structure dependence of its translation suggests two alternative modes of transcription initiation regulation, also proposed in the paper by A. Benecke in this issue for interpreting strikingly bimodal micro-array data.

Chromatin↗

[Baudot's code, weft of the genetic code].

Enumerating Bn numbers using only Bn figures is possible thanks to an overlapping reading of a cyclic sequence built according to Baudot's code. This code allows the genetic code to be screened to show the distribution of the synonyms of the aminoacids. The assignments of the genetic code obey strict laws of optimisation of resistance against the effects of mutations.

Amino Acid Sequence↗

Code type-specific tables for interpretation of MMPI-2 Harris and Lingoes subscales: consideration of gender and code type definition.

Normative tables for various MMPI-2 code types, which may be used to enhance the interpretation of the Harris and Lingoes subscales, were developed. It was found that scores on the subscales covaried significantly as a function of code type. Gender and code type definition strategy were considered as moderators of the relationship between code type and subscale scores, but neither accounted for a large enough proportion of variance to justify consideration in the tables.

Adult↗

Composite descriptions associated with rare MMPI two-point code types: codes that involve scale 5.

MMPI files of 1,016 prior patients were searched for protocols with two-point codes that involved scale 5. Sixty-one such protocols were found; these accounted for 6% of the sample. Salient characteristics of the cases were noted, and composite descriptions were developed for each of the code types. An additional 22 cases were located over the next 2 years in response to my requests for such profiles. Base rates from the original sample, as well as descriptive statistics and composite descriptions from the extended sample, are provided for each of the eight code types with the exception of the 5-0/0-5 code, which will be presented elsewhere.

Adult↗

A circular code in the protein coding genes of mitochondria.

A new maximal circular code X0(MIT) with two permutated maximal circular codes X1(MIT) and X2(MIT) is identified in the protein coding genes of mitochondria. The three subsets of 20 trinucleotides X0(MIT)={ACA, ACC, ATA, ATC, CTA, CTC, GAA, GAC, GAT, GCA, GCC, GCT, GGA, GGC, GGT, GTA, GTC, GTT, TTA, TTC}, X1(MIT) and X2(MIT) are in frame 0 (reading frame), 1 and 2 respectively. X1(MIT) and X2(MIT) are deduced by one and two circular permutations of X0(MIT) respectively. The code X0(MIT) has four important properties: a length of the minimal window to automatically retrieve frame 0 which is equal to five nucleotides; an occurrence probability equal to 6.3 x 10(-5); a low frequency (12% in average) of misplaced trinucleotides in the shifted frames; and an occurrence of four types of nucleotides in the first and second trinucleotide sites but no nucleotide G in the third trinucleotide site. Several biological consequences are presented in the Discussion.

Amino Acids↗

Diversity in isochore structure among cold-blooded vertebrates based on GC content of coding and non-coding sequences.

To review the general consideration about the different compositional structure of warm and cold-blooded vertebrates genomes, we used of the increasing number of genetic sequences, including coding (exons) and non-coding (introns) regions, that have been deposited on the databases throughout last years. The nucleotide distributions of the third codon positions (GC3) have been analyzed in 1510 coding sequences (CDS) of fish, 1414 CDS of amphibians and 320 CDS of reptiles. Also, the relationship between GC content of 74, 56 and 25 CDS of fish, amphibians and reptiles, respectively and that of their corresponding introns (GCI) have been considerated. In accordance with recent data, sequence analysis showed the presence of very GC3-rich CDS in these poikilotherm vertebrates. However, very high diversity in compositional patterns among different orders of fish, amphibians and reptiles was found. Significant positive correlations between GC3 and GCI was also confirmed for the genes analyzed. Nevertheless, introns resulted to be poorer in GC than their corresponding CDS, this difference being larger than in human genome. Because the limited number of available sequences including exons and introns we must be cautious about the results derived from them. However, the indicious of higher GC richness of coding sequences than of their corresponding introns could aid to understand the discrepancy of sequence analysis with the ultracentrifugation studies in cold-blooded vertebrates that did not predict the existence of GC-rich isochores.

Amphibians↗

Transfer RNA structure and coding specificity. II. A D-arm tertiary interaction that restricts coding range.

We investigated the structural basis of the kinetic effect on coding specificity by the D-arm mutant (G24 to A) of Escherichia coli tRNATrp. A set of tRNA genes with structural alterations in the D-arm was constructed by site-directed mutagenesis in vitro, and we determined the in vivo translational activities of these tRNAs. Our results suggest that a hydrogen-bond donor in the major groove of the D-helix at position 24 is required for the expansion of tRNA wobble coding specificity. From inspection of tRNA crystal structure, we identified a potential new tertiary pairing of base 24 with the base at position 9 (this base links the acceptor and D-stems). We constructed tRNAs with mutations at position 9 and showed that the phenotypes of position 11-24 D-arm mutants are indeed dependent on the identity of base 9. Our analysis of the effects of these mutations on the interactions of tRNA with the ribosome and with aminoacyl-tRNA synthetase suggests that the conformation or conformational dynamics of the middle of the tRNA molecule alters the kinetics of the interaction with the ribosomal coding site. The 9-23 and putative 9-24 tertiaries, and perhaps other normal tertiary interactions in this region, modulate these kinetics to increase or decrease coding specificity.

Amino Acyl-tRNA Synthetases↗

The accuracy of address coding and the effects of coding errors.

Studies that estimate the influence of characteristics of place on health often use geocoded addresses to identify location of study subjects. This study uses housing built before 1990 selected for the 1995-2001 National Health Interview Survey (N=252,421) to develop a standard against which geocodes obtained from an address-coding program are compared. The results show that geocoding is generally accurate and is more successful in urban areas. Blockgroups with missing codes are more rural and somewhat poorer than blockgroups with correct codes. The effect of incorrect codes on statistical analyses depends on the proportion rural in a study population.

Censuses↗

In-phase implies large likelihood for independent codon model: distinguishing coding from non-coding sequences.

It is proven that under the independent codon model, the likelihood of a DNA coding sequence read according to the correct frame is asymptotically larger than that read with an incorrect frame. Based on this proposition, a single set of probabilities of the codon usage is enough for discriminating the six frames of coding sequences under the independent codon model. The direct coding sequence of Escherichia coli genome is taken as an example to examine the codon independency by using the mutual information and chi2 analysis. The contrast between the coding frame and the two offset frames is evident. A self-learning approach for generating training set is proposed to estimate probability parameters.

Codon↗