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Results for “Genetic code”

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PubMed1991

Prebiotic co-evolution of self-replication and translation or RNA world?

A prebiotic scenario is proposed, based on the recent "domain hypothesis" model (Lahav, 1989, J. molec. Evol. 29, 475-479), suggested for domain propagation of RNA-like molecules in a fluctuating environment. The same system is suggested now not only for the evolution of ribozymes, but also for the evolution of directed peptide synthesis, as follows: Short, self-structured strands (termed prebioectons), each possessing a templatable domain which is chargeable by an amino acid, are the predecessors of tRNA (proto-tRNA). Complementary domains are formed on these prebioectons during an environmental cycle such as wetting-drying, followed by their dissociation from their template domain and ligation, to form the predecessor of mRNA (proto-mRNA). The evolution of directed peptide synthesis is suggested to be based on the ability of the charged prebioectons to attach preferentially to their complementary domains on the proto-mRNA. Two stages of this process are envisioned, namely: (a) Template-directed, random peptide synthesis taking place when non-specifically-charged prebioectons are sequentially attached each to its complementary domain on the proto-mRNA, followed by peptide bond formation. (b) Template-and-sequence-directed peptide synthesis, which can be realized after the "invention" of a catalytic molecule capable of specifically charging a proto-tRNA by an amino acid; this is the crucial evolutionary stage, where a crude genetic code becomes functional. Gradually, catalytic peptides and ribozymes are selected for their functions and evolve, while being encoded in the primitive "memory" of the emerging system. Thus, rather than the RNA monopoly postulated by the RNA World hypothesis, an early co-evolution of primitive enzymes and ribozymes is suggested.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

A simple way to look at DNA.

A method is presented for embedding nucleotide sequence data in a simple metric space. Computer graphical examination of spatially-represented sequences permits rapid searches for canonical patterns or interesting structures. Sequence comparisons are facilitated by plots of distance measures for homologous sequences, and the large-scale structure of the genetic code can be studied by measures such as fractal dimensionality.

Actins↗
PubMed1997

Cloning and expression of a cysteine-rich venom protein from Trimeresurus mucrosquamatus (Taiwan habu).

A full-length cDNA for cysteine-rich venom protein (CRVP) was constructed by immunoscreening and 5'-rapid amplification of cDNA ends from a cDNA library of venom gland of Trimeresurus mucrosquamatus. The predicted CRVP consisted of 183 amino acid residues including a putative signal peptide of 21 residues. Northern blot hybridization suggested the tissue-specific expression in venom gland and its corresponding length of cDNA. The predicted amino acid sequence of CRVP was homologous to a rat epididymal metalloprotein and a lizard helothermine. Amino acid sequence analysis suggested that CRVP may be a venom metalloprotein targeted against ryanodine receptors and Ca2+ release. Moreover, CRVP expressed in Escherichia coli exhibited the same antigenicity as their native venom forms of T. mucrosquamatus. This is the first report in the cloning and expression of a CRVP from the venom gland of T. mucrosquamatus.

Amino Acid Sequence↗
PubMed2004

Histone deacetylase inhibitors.

The base sequence of DNA provides the genetic code for proteins. The regulation of expression or suppression of gene transcription is largely determined by the structure of the chromatin--referred to as epigenetic gene regulation (Agalioti et al., 2002; Jenuwein and Allis, 2001; Richards and Elgin, 2002; Spotswood and Turner, 2002; Zhang and Reinberg, 2001). Posttranslational modifications of the histones of chromatin play an important role in regulating gene expression. Some of the most extensively studied epigenetic modifications involve acetylation/deacetylation of lysines in the tails of the core histones, which is controlled by the action of histone deacetylases (HDACs) and histone acetyltransferases (HATs). A controlled balance between histone acetylation and deacetylation appears to be essential for normal cell growth (Waterborg, 2002). Alterations in the structure or expression of HATs and HDACs occur in many cancers (Jones and Baylin, 2002; Marks et al., 2001, 2003; Timmermann et al., 2001; Wang et al., 2001). A structurally diverse group of molecules has been developed that can inhibit HDACs (HDACi) (Arts et al., 2003; Bouchain and Delorme, 2003; Curtin and Glaser, 2003; Johnstone and Licht, 2003; Marks et al., 2003; Remiszewski, 2003; Richon et al., 1998; Yoshida et al., 2003). These inhibitors induce growth arrest, differentiation, and?or apoptosis of cancer cells in vitro and in in vivo tumor-bearing animal models. Clinical trials with several of these agents have shown that certain HDACi have antitumor activity against various cancers at doses that are well tolerated by patients (Gottlicher et al., 2001; Kelly et al., 2002a,b; Piekarz et al., 2001; Wozniak et al., 1999).

Acetylation↗
PubMed1976

Repressors.

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Amino Acid Sequence↗
PubMed2001

The emergence of life on Earth.

Combined top-down and bottom-up research strategies and the principle of biological continuity were employed in an attempt to reconstruct a comprehensive origin of life theory, which is an extension of the coevolution theory (Lahav and Nir, Origins of Life Evol. Biosphere (1997) 27, 377-395). The resulting theory of emergence of templated-information and functionality (ETIF) addresses the emergence of living entities from inanimate matter, and that of the central mechanisms of their further evolution. It proposes the emergence of short organic catalysts (peptides and proto-ribozymes) and feedback-loop systems, plus their template-and-sequence-directed (TSD) reactions, encompassing catalyzed replication and translation of populations of molecules organized as chemical-informational feedback loop entities, in a fluctuating (wetting-drying) environment, functioning as simplified extant molecular-biological systems. The feedback loops with their TSD systems are chemically and functionally continuous with extant living organisms and their emergence in an inanimate environment may be defined as the beginning of life. The ETIF theory considers the emergence of bio-homochirality, a primordial genetic code, information and the incorporation of primordial metabolic cycles and compartmentation into the emerging living entities. This theory helps to establish a novel measure of biological information, which focuses on its physical effects rather than on the structure of the message, and makes it possible to estimate the time needed for the transition from the inanimate state to the closure of the first feedback-loop systems. Moreover, it forms the basis for novel laboratory experiments and computer modeling, encompassing catalytic activity of short peptides and proto-RNAs and the emergence of bio-homochirality and feedback-loop systems.

Biological Evolution↗
PubMed2000

Proteomics: new perspectives, new biomedical opportunities.

Proteomics-based approaches, which examine the expressed proteins of a tissue or cell type, complement the genome initiatives and are increasingly being used to address biomedical questions. Proteins are the main functional output, and the genetic code cannot always indicate which proteins are expressed, in what quantity, and in what form. For example, post-translational modifications of proteins, such as phosphorylation or glycosylation, are very important in determining protein function. Similarly, the effects of environmental factors or multigenic processes such as ageing or disease cannot be assessed simply by examination of the genome alone. This review describes the underlying technology and illustrates several areas of biomedical research, ranging from pathogenesis of neurological disorders to drug and vaccine design, in which potential clinical applications are being explored.

Animals↗
PubMed2006

Buruli ulcer: emerging from obscurity.

Buruli ulcer is a skin disease caused by infection with Mycobacterium ulcerans, which produces a potent toxin known as mycolactone, thus distinguishing itself from all other mycobacterial diseases. Mycolactone destroys cells in the subcutis, leading to the development of large ulcers with undermined edges. The genome sequence of M ulcerans has now been published and it transpires that two identical copies of a plasmid carry the genetic code for mycolactone. The mode of transmission of infection remains uncertain, although environmental sources of the organisms are now better understood. Considerable progress has been made in understanding the immune response to M ulcerans and there have been major advances in management of the disease with the introduction of rational antibiotic therapy. We summarise the current understanding of M ulcerans and its relations with human beings.

Adolescent↗
PubMed1969

The genes.

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Animals↗
PubMed1998

Heterogeneity in the circumsporozoite protein gene of Plasmodium malariae isolates from sub-Saharan Africa.

Polymorphism of the circumsporozoite protein (CSP) of Plasmodium malariae was characterized by comparing gene sequences of twelve field isolates obtained in Yaoundé, Cameroon, Central Africa, and one clinical isolate originating from Côte d'Ivoire, West Africa. The length of the CSP gene ranged from 1266 to 1302 bp. The size polymorphism was due to variation in the number of tandem repeat units. All P. malariae isolates displayed a highly conserved 5' non-repeat region. Seven non-synonymous and two synonymous nucleotide variations were observed in the 3' non-repeat region. In the deduced amino acid sequence the repetitive sequences consisted of a varying number of major (Asn Ala Ala Gly (NAAG); range between 42 and 46 units) and minor (Asn Asp Ala Gly (NDAG) or Asn Asp Gln Gly (NDEG); n = six or seven units) tetrapeptide units. None of the isolates had an identical sequence at nucleotide level. These findings suggest that polymorphism in CSP is essentially limited to the tandem repeat domain.

Animals↗