Genetic determinants coding for fimbriae and adhesins of extraintestinal Escherichia coli.
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Adhesins, Bacterial↗
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Can genetic material retrotransposition be a cause of pathology accompanying cerebral aneurysm rupture?
Our considerations were prompted by observation of patients who underwent surgery due to cerebral aneurysm rupture. Elevated anti-HIV antibody titers were detected in such patients. The above condition was not observed either in subjects with intracranial hemorrhages from cerebral angiomas. The observed titers remained certainly below the cut off level indicating contact with HIV. We analyzed the subpopulations of peripheral blood lymphocytes both in the surgery patients and in the control group represented by blood collected from blood donors. On the other hand, the proliferation potential of circulating lymphocytes in the blood of patients with subarachnoid hemorrhages due to cranial aneurysm ruptures was found to be decreased. Dislocation of transposons, so-called 'unauthorized recombination' is known to occur within the framework of genetic code pathology. Endogenous human viruses have been described, and they may be involved in the development of autoimmune disorders. Additionally, viruses involved in autoimmune processes, which may be 'identical' with retrotransposons, have been described. Moreover, there are studies demonstrating that AIDS is caused by retrotransposition of genetic code material fragments. Our considerations are substantiated by ultrastructural analyses of material coming from the gyrus rectus cortex fragments, resected in patients who underwent clipping of a ruptured aneurysm of the anterior communicating artery. We demonstrated in neuronal chromatin the presence of a molecule ca. 80 nm in diameter, corresponding with its size to retroviruses or genetic material molecules with altered substructure. The authors suggest a new mechanism of development of neurological deficits in patients with ruptured cerebral aneurysms.
Acquired Immunodeficiency Syndrome↗
[A distinctive scheme of amino acid replacement was evolved for the generation of diversity, among hypervariable positions (author's transl)].
The diversity of amino acid residues, at a same position when comparing several aligned polypeptide sequences, may be translated as follows. The way along which a given amino acid, A, is replaced--in average--by another amino acid, B, is characterized by a coefficient linked with the pair A-B. Thus, one given amino acid is given a "set" of 19 coefficients, and the 20 different such sets may be analyzed. This method applies to the analysis of the diversity, among different sequences VH and VL of the variable regions of immunoglobulin heavy chains and light chains. From an observation of the alterations of those different sets, according to the sample of positions from which they were derived, it is possible to reach to the following conclusions. A) In the first approximation, all the amino acids present the same behaviour, whichever the sample. The frequency of replacement of an amino acid, A, by another amino acid B, is mainly a function of the proportion of B in the sample. B) In the second approximation, a more elaborate scheme of replacement is apparent, and is linked with an equivalent scheme in the genetic code; it is shown that hypervariable positions as well as random positions in VH and VL obey to this scheme. C) In the third approximation, a complementary structure is observed, which only pertains to the sample of hypervariable positions, and which might constitute a peculiar aspect of a selective process: this complementary structure is quite diverging from the genetic code. This analysis brings a strong argument against somatic theories, for the generation of diversity.
Amino Acid Sequence↗
Mutually symmetric and complementary triplets: differences in their use distinguish systematically between coding and non-coding genomic sequences.
The general property of asymmetry in word use in meaningful texts written in a variety of languages, motivates a quantification of the differences in the use of mutually symmetric triplets in genomic sequences. When this is done in the three reading frames, high values found for one of them are used as indication that the sequence is coding for a protein. Moreover, a similar quantification of the differences in the use of complementary triplets is introduced, again with predictive power of the coding character of a sequence. This method reflects the non-equivalence between sense and anti-sense strand of a coding segment. In both approaches, "linguistic asymmetry" in coding sequences is related to the form of the genetic code and to the bias in codon usage and amino acid use skews.
Algorithms↗
Code domains in tandem repetitive DNA sequence structures.
Traditionally, many people doing research in molecular biology attribute coding properties to a given DNA sequence if this sequence contains an open reading frame for translation into a sequence of amino acids. This protein coding capability of DNA was detected about 30 years ago. The underlying genetic code is highly conserved and present in every biological species studied so far. Today, it is obvious that DNA has a much larger coding potential for other important tasks. Apart from coding for specific RNA molecules such as rRNA, snRNA and tRNA molecules, specific structural and sequence patterns of the DNA chain itself express distinct codes for the regulation and expression of its genetic activity. A chromatin code has been defined for phasing of the histone-octamer protein complex in the nucleosome. A translation frame code has been shown to exist that determines correct triplet counting at the ribosome during protein synthesis. A loop code seems to organize the single stranded interaction of the nascent RNA chain with proteins during the splicing process, and a splicing code phases successive 5' and 3' splicing sites. Most of these DNA codes are not exclusively based on the primary DNA sequence itself, but also seem to include specific features of the corresponding higher order structures. Based on the view that these various DNA codes are genetically instructive for specific molecular interactions or processes, important in the nucleus during interphase and during cell division, the coding capability of tandem repetitive DNA sequences has recently been reconsidered.
Animals↗
Darwinism and ethology. The role of natural selection in animals and humans.
The role of behaviour in biological evolution is examined within the context of Darwinism. All Darwinian models are based on the distinction of two mechanisms: one that permits faithful transmission of a feature from one generation to another, and another that differentially regulates the degree of this transmission. Behaviour plays a minimal role as an agent of transmission in the greater part of the animal kingdom; by contrast, the forms it may assume strongly influence the mechanisms of selection regulating the different rates of transmission. We consider the decisive feature of the human species to be the existence of a phenotypical system of cultural coding characterized by precision and reliability which are the distinctive feature of genetic coding in animals. We examine the consequences for the application of the Darwinian model to human history.
Animals↗
RNA editing in wheat mitochondria results in the conservation of protein sequences.
RNA editing is a process that results in the production of a messenger RNA with nucleotide sequences that differ from those of the template DNA, and provides another mechanism for modulating gene expression. The phenomenon was initially described in the mitochondria of protozoa. Here we report that RNA editing is also required for the correct expression of plant mitochondrial genes. It has previously been proposed that in plant mitochondria there is a departure from the universal genetic code, with CGG specifying tryptophan instead of arginine. This was because CGG codons are often found in plant mitochondrial genes at positions corresponding to those encoding conserved tryptophans in other organisms. We have now found, however, wheat mitochondrial gene sequences containing C residues that are edited to U residues in the corresponding mRNA sequences. In this way, CGG codons can be changed to UGG codons in the mRNA so that tryptophan may be encoded according to the universal genetic code. Furthermore, for each codon modification resulting from a C----U conversion that we studied, we found a corresponding change in the amino acid that was encoded. RNA editing in wheat mitochondria can thus maintain genetic information at the RNA level and as a result contribute to the conservation of mitochondrial protein sequences among plants.
Amino Acid Sequence↗
Mitochondrial COI sequences in mites: evidence for variations in base composition.
Studies of mitochondrial DNA sequences in a variety of animals have shown important differences between phyla, including differences in the genetic codes used, and varying constraints on base composition. In that respect, little is known of mites, an important and diversified group. We sequenced a portion (340 nt) of the cytochrome oxidase subunit I (COI) encoding gene in twenty species of phytophagous mites belonging to nine genera of the two families Tetranychidae and Tenuipalpidae. The mitochondrial genetic code used in mites appeared to be the same as in insects. As is generally also the case in insects, the mite sequences were very rich in A + T (75% on average), especially at the third codon position (94%). However, important variations of base composition were observed among mite species, one of them showing as little as 69% A + T. Variations of base composition occur mostly through synonymous transitions, and do not have detectable effects on polypeptide evolution in this group.
Animals↗
Reassessing the Dlx code: the genetic regulation of branchial arch skeletal pattern and development.
The branchial arches are meristic vertebrate structures, being metameric both between each other within the rostrocaudal series along the ventrocephalic surface of the embryonic head and within each individual arch: thus, just as each branchial arch must acquire a unique identity along the rostrocaudal axis, each structure within the proximodistal axis of an arch must also acquire a unique identity. It is believed that regional specification of metameric structures is controlled by the nested expression of related genes resulting in a regional code, a principal that is though to be demonstrated by the regulation of rostrocaudal axis development in animals exerted by the nested HOM-C/Hox homeobox genes. The nested expression pattern of the Dlx genes within the murine branchial arch ectomesenchyme has more recently led to the proposal of a Dlx code for the regional specification along the proximodistal axis of the branchial arches (i.e. it establishes intra-arch identity). This review re-examines this hypothesis, and presents new work on an allelic series of Dlx loss-of-function mouse mutants that includes various combinations of Dlx1, Dlx2, Dlx3, Dlx5 and Dlx6. Although we confirm fundamental aspects of the hypothesis, we further report a number of novel findings. First, contrary to initial reports, Dlx1, Dlx2 and Dlx1/2 heterozygotes exhibit alterations of branchial arch structures and Dlx2-/- and Dlx1/2-/- mutants have slight alterations of structures derived from the distal portions of their branchial arches. Second, we present evidence for a role for murine Dlx3 in the development of the branchial arches. Third, analysis of compound Dlx mutants reveals four grades of mandibular arch transformations and that the genetic interactions of cis first-order (e.g. Dlx5 and Dlx6), trans second-order (e.g. Dlx5 and Dlx2) and trans third-order paralogues (e.g. Dlx5 and Dlx1) result in significant and distinct morphological differences in mandibular arch development. We conclude by integrating functions of the Dlx genes within the context of a hypothesized general mechanism for the establishment of pattern and polarity in the first branchial arch of gnathostomes that includes regionally secreted growth factors such as Fgf8 and Bmp and other transcription factors such as Msx1, and is consistent both with the structure of the conserved gnathostome jaw bauplan and the elaboration of this bauplan to meet organismal end-point designs.
Animals↗
A new substitution matrix for protein sequence searches based on contact frequencies in protein structures.
The instabilities of the native structures of mutant proteins with an amino acid exchange are estimated by using the contact energy and the number of contacts for each type of amino acid pair, which were estimated from 18,192 residue-residue contacts observed in 42 crystals of globular proteins. They were then used to evaluate a transition probability matrix of codon substitutions and a log relatedness odds matrix, which is used as a scoring matrix to measure the similarity between protein sequences. To consider amino acid substitutions in homologous proteins, base mutation rates and the effects of the genetic code are also taken into account. The average fitness of an amino acid exchange is approximated to be proportional to the structural stability of the mutant protein, which is then approximated by the average energy change of the protein native structure expected for the amino acid exchange with neglect of the energy change of the denatured state. In global and local homology searches, this scoring matrix tends to yield significantly higher alignment scores than either the unitary matrix or the genetic code matrix, and also may yield higher alignment scores for distantly related protein pairs than MDM78. One of advantages of this scoring matrix is that the equilibrium frequencies of codons and also base mutation rates can be adjusted.
Codon↗
Eukaryotes versus prokaryotes: an estimate of evolutionary distance.
The divergence of nucleated organisms and bacteria was 2.6 times more remote in evolution than the divergences of the nucleated organisms into sparate kingdoms, as evidenced by genetic changes in cytochrome c and transfer RNA. The development of the genetic code through the differentiation of transfer RNA's for different amino acids was still more remote in evolution. The overall states of transfer RNA evolution in bacteria and nucleated organisms were comparable.
Bacteria↗
Expression of a ciliate gene in Escherichia coli using a suppressor tRNA to read the UAA and UAG glutamine codons.
Most ciliates use a particular genetic code where the standard stop codons UAA and UAG encode glutamine. Ciliate genes cannot therefore be expressed in heterologous systems such as Escherichia coli. To overcome this problem, we worked out a system of inducible suppression to permit efficient readthrough of UAAs and UAGs: a strong UAA tRNA suppressor that inserts glutamic acid was cloned downstream from a tac promoter whose efficiency was reduced by a transcription terminator. This system proved to be operational (1) to suppress UAG mutations by wobble pairing in an E. coli lacI-lacZ gene fusion and (2) to read through at least eight UAA glutamine codons in a Paramecium alpha-tubulin gene, as detected by Western blotting and colony hybridization. This work opens the way for cloning Ciliate genes from expression libraries and for expressing particular sequences without extended in vitro mutagenesis. A similar approach can be envisaged for expression of genes from Mycoplasma, mitochondria or other genomes that use non-standard genetic codes.
Animals↗
Prions: an evolutionary perspective.
Studies in both prion-due diseases in mammals and some non-Mendelian hereditary processes in yeasts have demonstrated that certain proteins are able to transmit structural information and self-replication. This induces the corresponding conformational changes in other proteins with identical or similar sequences. This ability of proteins may have been very useful during prebiotic chemical evolution, prior to the establishment of the genetic code. During this stage, proteins (proteinoids) must have molded and selected their structural folding units through direct interaction with the environment. The proteinoids that acquired the ability to propagate their conformations (which we refer to as conformons) would have acted as reservoirs and transmitters of a given structural information and hence could have acted as selectors for conformational changes. Despite the great advantage that arose from the establishment of the genetic code, the ability to propagate conformational changes did not necessarily disappear. Depending on the degree of involvement of this capacity in biological evolution, we propose two not mutually exclusive hypotheses: (i) extant prions could be an atavism of ancestral conformons, which would have co-evolved with cells, and (ii) the evolution of conformons would have produced cellular proteins, able to transmit structural information, and, in some cases, participating in certain processes of regulation and epigenesis. Therefore, prions could also be seen as conformons of a conventional infectious agent (or one that co-evolved with it independently) that, after a longer or shorter adaptive period, would have interacted with conformons from the host cells.
Biological Evolution↗
On the plausibility of a UV transparent biochemistry.
Some molecules, particularly aromatics, have high molar extinction coefficients at wavelengths in the damaging ultraviolet radiation region of the spectrum between 200 and 400 nm. Thus, under a UV radiation flux in which these wavelengths are represented, it could be argued that a selection pressure would exist for a UV transparent biochemistry in which they were not represented. This hypothesis is explored using data made available from proteomics, focusing particularly on tryptophan, against which a selection pressure could exist on present-day Earth as a result of its absorbance shoulder at wavelengths greater than 290 nm. The abundance of tryptophan in whole proteomes is lower than expected from the degeneracy of the genetic code. A lower usage of tryptophan is found in the cytochrome c oxidase polypeptide I of UV-exposed organisms compared to nocturnal and subterranean organisms, but not in ATP synthase chain A. Examination of the amino acid composition of photolyase, an enzyme that requires exposure to light to function, shows that the tryptophan abundances exceed those of the total proteome of most organisms and the abundances expected from the degeneracy of the genetic code. This is also true for cytochrome c oxidase, another enzyme that makes extensive use of the electron transfer properties of tryptophan. We suggest that the selection pressure for the use of tryptophan caused, among other factors, by the uses of delocalised pi-electrons that this aromatic provides in active sites and binding motifs outweighs the selection pressure for UV transparency. This trade-off explains the lack of conclusive evidence for a UV transparent selection pressure. We suggest that this trade-off applies to the stacked pi-electrons of DNA. It offers a solution to the long-standing paradox of why the macromolecule responsible for the faithful replication of information has high absorbance in the damaging UV radiation region of the spectrum.
Amino Acids↗
[The jockey mobile genetic element codes a DNA polymerase similar to retroviral reverse transcriptase].
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Amino Acid Sequence↗
Greater GNN pattern bias in sequence elements encoding conserved residues of ancient proteins may be an indicator of amino acid composition of early proteins.
The possibility that RNY pattern bias in extant sequences is a remnant of more pronounced bias of this type in early ancestors was investigated. To this end, conserved residues (those residues for which the inferred ancestral and known descendant amino acids are identical) and non-conserved residues of ancient proteins dating to the Last Universal Ancestor were identified within six species: two archaea, two eubacteria and two eukaryotes. Bias within sequence elements encoding each subset of residues, conserved and non-conserved, was then determined. In all species, GNN bias is greater within conserved than non-conserved sequence elements, whereas ANN is not. This difference is statistically significant in all six species examined. Since the relative mutability of the GNN-encoded amino acids does not explain the greater bias in conserved sequences, it is concluded that early sequences probably possessed a strong GNN bias. It is suggested that this bias may be a consequence of the GNN codons being the first introduced into the genetic code. Although NNY bias is also greater within conserved sequence elements of the six species, that difference is statistically significant in only half of them. Therefore, the evidence for early NNY bias remains inconclusive. The findings of this study do not support the proposal of Diaz-Lazcoz et al. (J. Mol. Biol. 250 (1995) 123) that the codons of the TCN four-codon block were the first assigned to serine during the evolution of the genetic code.
Amino Acids↗
Frequent occurrence of recognition site-like sequences in the restriction endonucleases.
BACKGROUND: There are two different theories about the development of the genetic code. Woese suggested that it was developed in connection with the amino acid repertoire, while Crick argued that any connection between codons and amino acids is only the result of an "accident". This question is fundamental to understand the nature of specific protein-nucleic acid interactions. RESULTS: The nature of specific protein-nucleic acid interaction between restriction endonucleases (RE) and their recognition sequences (RS) was studied by bioinformatics methods. It was found that the frequency of 5-6 residue long RS-like oligonucleotides is unexpectedly high in the nucleic acid sequence of the corresponding RE (p < 0.05 and p < 0.001 respectively, n = 7). There is an extensive conservation of these RS-like sequences in RE isoschizomers. A review of the seven available crystallographic studies showed that the amino acids coded by codons that are subsets of recognition sequences were often closely located to the RS itself and they were in many cases directly adjacent to the codon-like triplets in the RS.Fifty-five examples of this codon-amino acid co-localization are found and analyzed, which represents 41.5% of total 132 amino acids which are localized within 8 A distance to the C1' atoms in the DNA. The average distance between the closest atoms in the codons and amino acids is 5.5 +/- 0.2 A (mean +/- S.E.M, n = 55), while the distance between the nitrogen and oxygen atoms of the co-localized molecules is significantly shorter, (3.4 +/- 0.2 A, p < 0.001, n = 15), when positively charged amino acids are involved. This is indicating that an interaction between the nucleic- and amino acids might occur. CONCLUSION: We interpret these results in favor of Woese and suggest that the genetic code is "rational" and there is a stereospecific relationship between the codes and the amino acids.
Amino Acids↗
Post-transfer editing in vitro and in vivo by the beta subunit of phenylalanyl-tRNA synthetase.
Translation of the genetic code requires attachment of tRNAs to their cognate amino acids. Errors during amino-acid activation and tRNA esterification are corrected by aminoacyl-tRNA synthetase-catalyzed editing reactions, as extensively described for aliphatic amino acids. The contribution of editing to aromatic amino-acid discrimination is less well understood. We show that phenylalanyl-tRNA synthetase misactivates tyrosine and that it subsequently corrects such errors through hydrolysis of tyrosyl-adenylate and Tyr-tRNA(Phe). Structural modeling combined with an in vivo genetic screen identified the editing site in the B3/B4 domain of the beta subunit, 40 angstroms from the active site in the alpha subunit. Replacements of residues within the editing site had no effect on Phe-tRNA(Phe) synthesis, but abolished hydrolysis of Tyr-tRNA(Phe) in vitro. Expression of the corresponding mutants in Escherichia coli significantly slowed growth, and changed the activity of a recoded beta-galactosidase variant by misincorporating tyrosine in place of phenylalanine. This loss in aromatic amino-acid discrimination in vivo revealed that editing by phenylalanyl-tRNA synthetase is essential for faithful translation of the genetic code.
Escherichia coli↗