Extracellular nucleic acids are found in different biological fluids in the organism and in the environment: DNA is a ubiquitous component of the organic matter pool in the soil and in all marine and freshwater habitats. Data from recent studies strongly suggest that extracellular DNA and RNA play important biological roles in microbial communities and in higher organisms. DNA is an important component of bacterial biofilms and is involved in horizontal gene transfer. In recent years, the circulating extracellular (...) class='Hi'>nucleic acids were shown to be associated with some diseases. Attempts are being made to develop noninvasive methods of early tumor diagnostics based on analysis of circulating DNA and RNA. Recent observations demonstrated the possibility of nucleic acids exchange between eukaryotic cells and extracellular space suggesting their participation in so far unidentified biological processes. BioEssays 29:654–667, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Enzymes that degrade nucleic acids are emerging as important players in the pathogenesis of inflammatory disease. This is exemplified by the recent identification of four genes that cause the childhood inflammatory disorder, Aicardi‐Goutières syndrome (AGS). This is an autosomal recessive neurological condition whose clinical and immunological features parallel those of congenital viral infection. The four AGS genes encode two nucleases: TREX1 and the hetero‐trimeric Ribonuclease H2 (RNase H2) complex. The biochemical activity of these enzymes was initially characterised 30 years (...) ago but a role in neurological inflammation was entirely unanticipated until they were found to be mutated in AGS. This has led to a hypothesis that accumulation of intracellular nucleic acids occurs as a consequence of mutation in these enzymes and triggers an inflammatory response through activation of innate immune pattern recognition receptors. ©2007 Wiley Periodicals, Inc BioEssays 30:833–842, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Nucleic acid hybridization is being increasingly used in viral diagnosis. Most of the assays described so far for this purpose require the use of radioactive probes. Their replacement by Non‐radioactive assays has many advantages and makes the technique feasible in routine diagnostic work. Non‐radioactive assays have had limited use but their diagnostic value has been demonstrated for a number of virus infections. They have the main advantages of employing stable probes, of avoiding safety hazards and of being easy (...) and rapid to perform with limited laboratory facilities. Their main disadvantage compared to radioactive assays is in having relatively low sensitivity. Improvements in probe construction, in labelling and detecting methods, in sample treatment and in hybridization conditions may well increase their usefulness. (shrink)

There is growing evidence of evolutionary genome plasticity. The evolution of repetitive DNA elements, the major components of most eukaryotic genomes, involves the amplification of various classes of mobile genetic elements, the expansion of satellite DNA, the transfer of fragments or entire organellar genomes and may have connections with viruses. In addition to various repetitive DNA elements, a plethora of large and small RNAs migrate within and between cells during individual development as well as during evolution and contribute to changes (...) of genome structure and function. Such migration of DNA and RNA molecules often results in horizontal gene transfer, thus shaping the whole genomic network of interconnected species. Here, we propose that a high evolutionary dynamism of repetitive genome components is often related to the migration/movement of DNA or RNA molecules. We speculate that the cytoplasm is probably an ideal compartment for such evolutionary experiments. (shrink)

The central dogma of molecular biology dictates that, with only a few exceptions, information proceeds from DNA to protein through an RNA intermediate. Examining the enigmatic steps from prebiotic to biological chemistry, we take another road suggesting that primordial peptides acted as template for the self-assembly of the first nucleic acids polymers. Arguing in favour of a sort of archaic “reverse translation” from proteins to RNA, our basic premise is a Hadean Earth where key biomolecules such as amino acids, (...) polypeptides, purines, pyrimidines, nucleosides and nucleotides were available under different prebiotically plausible conditions, including meteorites delivery, shallow ponds and hydrothermal vents scenarios. Supporting a protein-first scenario alternative to the RNA world hypothesis, we propose the primeval occurrence of short two-dimensional peptides termed “selective amino acid- and nucleotide-matching oligopeptides” (henceforward SANMAOs) that noncovalently bind at the same time the polymerized amino acids and the single nucleotides dispersed in the prebiotic milieu. In this theoretical paper, we describe the chemical features of this hypothetical oligopeptide, its biological plausibility and its virtues from an evolutionary perspective. We provide a theoretical example of SANMAO’s selective pairing between amino acids and nucleosides, simulating a poly-Glycine peptide that acts as a template to build a purinic chain corresponding to the glycine’s extant triplet codon GGG. Further, we discuss how SANMAO might have endorsed the formation of low-fidelity RNA’s polymerized strains, well before the appearance of the accurate genetic material’s transmission ensured by the current translation apparatus. (shrink)

Structures of multisubunit RNA polymerases strongly differ from the many known structures of single subunit DNA and RNA polymerases. However, in functional complexes of these diverse enzymes, nucleic acids take a similar course through the active center. This finding allows superposition of diverse polymerases and reveals features that are functionally equivalent. The entering DNA duplex is bent by almost 90° with respect to the exiting template–product duplex. At the point of bending, a dramatic twist between subsequent DNA template bases (...) aligns the “coding“ base with the binding site for the incoming nucleoside triphosphate (NTP). The NTP enters through an opening that is found in all polymerases, and, in most cases, binds between an α‐helix and two catalytic metal ions. Subsequent phosphodiester bond formation adds a new base pair to the exiting template–product duplex, which is always bound from the minor groove side. All polymerases may undergo “induced fit” upon nucleic acid binding, but the underlying conformational changes differ. BioEssays 24:724–729, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

The series Topics in Current Chemistry presents critical reviews of the present and future trends in modern chemical research. The scope of coverage is all areas of chemical science including the interfaces with related disciplines such as biology, medicine and materials science. The goal of each thematic volume is to give the non-specialist reader, whether in academia or industry, a comprehensive insight into an area where new research is emerging which is of interest to a larger scientific audience. Each review (...) within the volume critically surveys one aspect of that topic and places it within the context of the volume as a whole. The most significant developments of the last 5 to 10 years are presented using selected examples to illustrate the principles discussed. The coverage is not intended to be an exhaustive summary of the field or include large quantities of data, but should rather be conceptual, concentrating on the methodological thinking that will allow the non-specialist reader to understand the information presented. Contributions also offer an outlook on potential future developments in the field. Review articles for the individual volumes are invited by the volume editors. Readership: research chemists at universities or in industry, graduate students. (shrink)

In this essay, we consider helicases, defined as enzymes that use the free energies of binding and hydrolysis of ATP to drive the unwinding of double‐stranded nucleic acids, and ask how they function within, and are “coupled” to, the macromolecular machines of gene expression. To illustrate the principles of the integration of helicases into such machines, we consider the macromolecular complexes that direct and control DNA replication and DNA‐dependent RNA transcription, and use these systems to illustrate how machines centered (...) around coupled polymerase–helicase systems can be regulated by small changes in the interactions of their functional components. BioEssays 25:1168–1177, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

In addition to their function in transport of water, ions, small metabolites, and growth factors in normal plant tissue, the plasmodesmata presumably serve as routes for cell‐to‐cell movement of plant viruses in infected tissue. Virus cell‐to‐cell spread through plasmodesmata is an active process mediated by specialized virus encoded movement proteins; however, the mechanism by which these proteins operate is not clear. We incorporate recent information on the biochemical properties of plant virus movement proteins and their interaction with plasmodesmata in a (...) model for transport of nucleic acids through plasmodesmatal channels. We propose that only single stranded (ss) nucleic acids can be transported efficiently through plasmodesmata, and that movement proteins function as molecular chaperones for ss nucleic acids to form unfolded movement protein‐ss nucleic acid complexes. These complexes are targeted to plasmodesmata. Plasmodesmatal permeability is then increased following interaction with movement protein and the entire movement complex or its nucleic acid component is translocated across the plasmodesmatal channel. (shrink)

The Y‐box proteins are the most evolutionarily conserved nucleic acid binding proteins yet defined in bacteria, plants and animals. The central nucleic acid binding domain of the vertebrate proteins is 43% identical to a 70‐amino‐acid‐long protein (CS7.4) from E. coli. The structure of this domain consists of an antiparallel fivestranded β‐barrel that recognizes both DNA and RNA. The diverse biological roles of these Y‐box proteins range from the control of the E. coli cold‐shock stress response (...) to the translational masking of messenger RNA in vertebrate gametes. This review discusses the organization of the prokaryotic and eukaryotic Y‐box proteins, how they interact with nucleic acids, and their biological roles, both proven and potential. (shrink)

In human cancers, histone methyltransferase SETDB1 (SET domain, bifurcated 1) is frequently overexpressed but its significance in carcinogenesis remains elusive. A recent study shows that SETDB1 downregulation induces de‐repression of retroelements and innate immunity in cancer cells. The possibility of SETDB1 functioning as a surveillant of retroelement expression is discussed in this study: the cytoplasmic presence of retroelement‐derived nucleic acids (RdNAs) drives SETDB1 into the nucleus by the RNA‐interference route, rendering the corresponding retroelement transcriptionally inert. These RdNAs could, therefore, (...) be signals of genome instability sent out for SETDB1 present in the cytoplasm to maintain genome integrity. (shrink)

Divergent evolution can explain how many proteins containing structurally similar domains, which perform a variety of related functions, have evolved from a relatively small number of modules or protein domains. However, it cannot explain how protein domains with similar, but distinguishable, functions and similar, but distinguishable, structures have evolved. Examples of this are the RNA‐binding proteins containing the RNA‐binding domain (RBD), and a newly established protein group, the cold‐shock domain (CSD) protein family. Both protein domains contain conserved RNP motifs on (...) similar single‐stranded nucleic acid‐binding surfaces. Apart from the RNP motifs, which have a similar function, the two families show little similarity in topology or amino acid sequence. This can be considered an interesting example of convergent evolution at the molecular level. Previously, a β‐sheet surface was found to interact with RNA in non‐homologous proteins from yeast, phage and man, revealing that this mode of RNA binding may be a widely recurring theme. (shrink)

Oxidative damage to DNA appears to be a factor in cancer, yet explanations for why highly elevated levels of such lesions do not always result in cancer remain elusive. Much of the genome is non‐coding and lesions in these regions might be expected to have little biological effect, an inference supported by observations that there is preferential repair of coding sequences. RNA has an important coding function in protein synthesis, and yet the consequences of RNA oxidation are largely unknown. Some (...) non‐coding nucleic acid is functional, e.g. promoters, and damage to these sequences may well have biological consequences. Similarly, oxidative damage to DNA may promote microsatellite instability, inhibit methylation and accelerate telomere shortening. DNA repair appears pivotal to the maintenance of genome integrity, and genetic alterations in repair capacity, due to single nucleotide polymorphisms or mutation, may account for inter‐individual differences in cancer susceptibility. This review will survey these aspects of oxidative damage to nucleic acids and their implication for disease. BioEssays 26:533–542, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

The generation of viral mutants in vitro was demonstrated by treatment of the isolated RNA of Tobacco Mosaic Virus by nitrous acid. This agent causes deaminations converting cytosine into uracil, and adenine into hypoxanthine. Our assay for mutagenesis was the production of local lesions on a tobacco variety on which the untreated strain produces systemic infections only. A variety of different mutants are generated in this way. Quantitative analysis of the kinetics of mutagenesis leads to the conclusion that alteration (...) of a single out of the 6000 nucleotides of the viral RNA is sufficient for causing a mutation. (shrink)

Flap EndoNuclease‐1 (FEN‐1) is a multifunctional and structure‐specific nuclease involved in nucleic acid processing pathways. It plays a critical role in maintaining human genome stability through RNA primer removal, long‐patch base excision repair and resolution of dinucleotide and trinucleotide repeat secondary structures. In addition to its flap endonuclease (FEN) and nick exonuclease (EXO) activities, a new gap endonuclease (GEN) activity has been characterized. This activity may be important in apoptotic DNA fragmentation and in resolving stalled DNA replication forks. (...) The multiple functions of FEN‐1 are regulated via several means, including formation of complexes with different protein partners, nuclear localization in response to cell cycle or DNA damage and post‐translational modifications. Its functional deficiency is predicted to cause genetic diseases, including Huntington's disease, myotonic dystrophy and cancers. This review summarizes the knowledge gained through efforts in the past decade to define its structural elements for specific activities and possible pathological consequences of altered functions of this multirole player. BioEssays 27:717–729, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

Famously, James Watson credited the discovery of the double-helical structure of DNA in 1953 to an X-ray diffraction photograph taken by Rosalind Franklin. Historians of molecular biology have long puzzled over a remarkably similar photograph taken two years earlier by the physicist and pioneer of protein structure William T. Astbury. They have suggested that Astbury’s failure to capitalize on the photograph to solve DNA’s structure was due either to his being too much of a physicist, with too little interest in (...) or knowledge of biology, or to his being misled by an erroneous theoretical model of the gene. Drawing on previously unpublished archival sources, this paper offers a new analysis of Astbury’s relationship to the problem of DNA’s structure, emphasizing a previously overlooked element in Astbury’s thinking: his concept of biological specificity. (shrink)

The universally recognized backbone of molecular biology describes the flow of genetic information from deoxyribonucleic acid (DNA) to ribonucleic acid (RNA) to protein or gene product, that is, DNA is transcribed into another nucleic acid (RNA), which is single stranded, next some types of RNA are in turn translated into proteins. Translation of nucleic acids to proteins is literally a translation from the genomic language to the metabolic language. Codons formed of a sequence (...) of three nucleic acids summon a specific amino acid. Translation from codons to proteins, that is, protein synthesis, takes place by specialized machinery comprising mRNA, ribosomes, and free amino acids. Inferring the structure of DNA opened the door for tremendous advances in understanding the role of genes in creating life, directing replication, and ongoing metabolic processes responsible for maintaining life at both the cellular and organism level. (shrink)

Progress in molecular biology has revealed profound relations between linguistic and genomic sciences, mainly through advances in bioinformatics. The structural symmetries between biochemical and verbal syntaxes raise the question of their origins: did they emerge independently, or did one arise from the other? Does the genetic code contain the traces of a protolanguage, a universal grammar whose gradual evolution and successive mutations progressively led to the polymorphism of natural languages? To explore this question, we review the isomorphism of the genetic (...) code and verbal codes from lexical, syntactic, semantic and pragmatic standpoints. We discuss the limits of these symmetries and their anthropomorphic connotations. We observe the gradual evolution of species and languages according to parallel mechanisms, and the genetic roots of the physiology of language. In conclusion, we hypothesize that human observers may not be projecting linguistic frameworks onto genomic structures. Rather, it could be their linguistic faculties that reflect the grammatical structure of genetic code. (shrink)

Upon separation of the protein from the nucleic acid component of tobacco mosaic virus by phenol, using a fast and gentle procedure, the nucleic acid is infective in assays on tobacco leaves. A series of qualitative and quantitative control experiments demonstrates that the biological activity cannot depend on residual proteins in the preparation, but is a property of isolated nucleic acid which is thus the genetic material of the virus.

Acidic substances were known for thousands of years, and their macroscopic-sensory characteristics were reflected by words in most ancient languages. In the Western canon, the history of the concept of acidity goes back to Ancient Greece. In Greek, the word associated with acidity from its early literary references was ὀξύς (“sharp”), and still in contemporary Greek the words “sour” and “acidic” have the same root. This paper makes a short presentation of the appearance of the abstract concept in the works (...) of Plato and Aristotle and relates it, on one side to the already existing theological-philosophical tradition, starting with Hesiod´s Theogony and on the other, to the then available to the Greeks organoleptic experiences of sourness-vinegar and sour milk. (shrink)

Environmentally we seem to be both the victims and the perpetrators of a type of bait and switch: lured into the discussion by one set of intuitions, our interests become redescribed in terms that are intellectually more respectable. Our deepest concerns with the environment are converted into foreign discourses, as we strain to make the languages of science, economics, and interest group politics express our intuitions. The circumscription of environmental philosophy within environmental ethics is one manifestation of this process of (...) bait and switch. 'Corrosive Effects' critiques this process through a case study of acid mine drainage-water pollution resulting from mining activities. An analysis of acid mine drainage reveals the metaphysical and theological roots of many of our environmental problems. (shrink)

This is a jointly written paper. It has two parts: an empirical part and a theoretical one. Part one, the empirical part, is written by Adrienne Lehrer and describes the language of taste, illustrated by the vocabulary for wine language. The language of the taste of wine often has both a descriptive and evaluate element. Using wine talk as an example, one wine may be described as fruity, acidic, and light, and another as sour, unbalanced, and thin. (...) The second uses highly evaluative terms not found in the first. We analyze the structure of the semantic field of wine descriptors, both literal and metaphoric. A heavy wine uses a deal metaphor, but recent wine writers have expanded the vocabulary by terms such as brawny and muscular. The authority of experts, the advantages and pitfalls thereof, in the description of wine is considered as an instance of delegation of semantic authority. Part two, written by Keith Lehrer, deals with the theoretical implications for a theory of meaning. The theory of wo... (shrink)

Synthetic biologists try to engineer useful biological systems that do not exist in nature. One of their goals is to design an orthogonal chromosome different from DNA and RNA, termed XNA for xeno nucleic acids. XNA exhibits a variety of structural chemical changes relative to its natural counterparts. These changes make this novel information‐storing biopolymer “invisible” to natural biological systems. The lack of cognition to the natural world, however, is seen as an opportunity to implement a genetic firewall that (...) impedes exchange of genetic information with the natural world, which means it could be the ultimate biosafety tool. Here I discuss, why it is necessary to go ahead designing xenobiological systems like XNA and its XNA binding proteins; what the biosafety specifications should look like for this genetic enclave; which steps should be carried out to boot up the first XNA life form; and what it means for the society at large. (shrink)

The use of molecules and reactions as evidence, markers and/or traits for evolutionary processes has a history more than a century long. Molecules have been used in studies of intra-specific variation and studies of similarity among species that do not necessarily result in the analysis of phylogenetic relations. Promoters of the use of molecular data have sustained the need for quantification as the main argument to make use of them. Moreover, quantification has allowed intensive statistical analysis, as a condition and (...) a product of increasing automation. All of these analyses are subject to the methodological anxiety characteristic of a community in search of objectivity. It is in this context that scientists compared and evaluated protein and nucleic acid sequence data with other types of molecular data – including immunological, electrophoretic and hybridization data. This paper argues that by looking at long-term historical processes, such as the use of molecular evidence in evolutionary biology, we gain valuable insights into the history of science. In that sense, it accompanies a growing concern among historians for big-pictures of science that incorporate the fruitful historical research on local cases of the last decades. (shrink)

The article deals with the notion of the genetic code and its metaphorical understanding as a “language”. In the traditional view of the language metaphor of the genetic code, combinations of nucleotides are signs of amino acids. Similarly, words combined from letters represent certain meanings. The language metaphor of the genetic code, 171–200, 2011) assumes that the nucleotides stay in the analogy to letters, triples to words and genes to sentences. We propose an application of mathematical linguistic (...) methods on the notion of the genetic code. We provide quantitative analysis of mRNA strings and natural language texts. This analysis is sensitive to the detection of the code units hierarchy. We also take into consideration a representative quantitative analysis of DNA, RNA and proteins. Our analysis of mRNA confirms an assumption that the design of the genetic code cannot analogize DNA bases and letters. The notion of the letter is much more appropriate if analogized with triplets or amino acids, 187–191, 2017). (shrink)

Life on earth is bound together by a common heritage, centered around a molecule that is present in almost every living cell of every living creature. Deoxyribonucleic acid (DNA), composed of four base pairs, the nucleic acids thymine, adenine, cytosine, and guanine, encodes the data that directs, in conjunction with the environment, the development and metabolism of all nondependent living creatures. Except for some viruses that rely only on ribonucleic acid (RNA), all living things are built by (...) the interaction of DNA and RNA within cells and their environments. There is no worldwide consensus yet as to whether portions of the human genome should be granted intellectual property protection, as indeed they are in the United States and a number of other nations. DNA posed numerous challenges to the legal framework for patent protection and may suggest developing an entirely new social and legal category recognizing its uniqueness. (shrink)

Basic proteins and nucleic acids are assembled into complexes in a reaction that must be facilitated by nuclear chaperones in order to prevent protein aggregation and formation of non‐specific nucleoprotein complexes. The nucleophosmin/nucleoplasmin (NPM) family of chaperones [NPM1 (nucleophosmin), NPM2 (nucleoplasmin) and NPM3] have diverse functions in the cell and are ubiquitously represented throughout the animal kingdom. The importance of this family in cellular processes such as chromatin remodeling, genome stability, ribosome biogenesis, DNA duplication and transcriptional regulation has led (...) to the rapid growth of information available on their structure and function. The present review covers different aspects related to the structure, evolution and function of the NPM family. Emphasis is placed on the long‐term evolutionary mechanisms leading to the functional diversification of the family members, their role as chaperones (particularly as it pertains to their ability to aid in the reprogramming of chromatin), and the importance of NPM2 as an essential component of the amphibian chromatin remodeling machinery during fertilization and early embryonic development. BioEssays 29: 49–59, 2007. © 2006 Wiley Periodicals, Inc. (shrink)

Advocates of an ‘extended evolutionary synthesis’ have claimed that standard evolutionary theory fails to accommodate epigenetic inheritance. The opponents of the extended synthesis argue that the evidence for epigenetic inheritance causing adaptive evolution in nature is insufficient. We suggest that the ambiguity surrounding the conception of the gene represents a background semantic issue in the debate. Starting from Haig’s gene-selectionist framework and Griffiths and Neumann-Held’s notion of the evolutionary gene, we define senses of ‘gene’, ‘environment’, and ‘phenotype’ in a way (...) that makes them consistent with gene-centric evolutionary theory. We argue that the evolutionary gene, when being materialized, need not be restricted to nucleic acids but can encompass other heritable units such as epialleles. If the evolutionary gene is understood more broadly, and the notions of environment and phenotype are defined accordingly, current evolutionary theory does not require a major conceptual change in order to incorporate the mechanisms of epigenetic inheritance. _1_ Introduction _2_ The Gene-centric Evolutionary Theory and the ‘Evolutionary Gene’ _2.1_ The evolutionary gene _2.2_ Genes, phenotypes, and environments _3_ Epigenetic Inheritance and the Gene-Centred Framework _3.1_ Treating the gene as the sole heritable material? _3.2_ Epigenetics and phenotypic plasticity _4_ Conclusion. (shrink)

An assessment is offered of the recent debate on information in the philosophy of biology, and an analysis is provided of the notion of information as applied in scientific practice in molecular genetics. In particular, this paper deals with the dependence of basic generalizations of molecular biology, above all the 'central dogma', on the socalled 'informational talk'. It is argued that talk of information in the 'central dogma' can be reduced to causal claims. In that respect, the primary aim of (...) the paper is to consider a solution to the major difficulty of the causal interpretation of genetic information: how to distinguish the privileged causal role assigned to nucleic acids, DNA in particular, in the processes of replication and protein production. A close reading is proposed of Francis H. C. Crick's On Protein Synthesis and related works, to which we owe the first explicit definition of information within the scientific practice of molecular biology. (shrink)