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)

Cells are cognitive entities possessing great computational power. DNA serves as a multivalent information storage medium for these computations at various time scales. Information is stored in sequences, epigenetic modifications, and rapidly changing nucleoprotein complexes. Because DNA must operate through complexes formed with other molecules in the cell, genome functions are inherently interactive and involve two-way communication with various cellular compartments. Both coding sequences and repetitive sequences contribute to the hierarchical systemic organization of the genome. By virtue of nucleoprotein (...) complexes, epigenetic modifications, and natural genetic engineering activities, the genome can serve as a read-write storage system. An interactive informatic conceptualization of the genome allows us to understand the functional importance of DNA that does not code for protein or RNA structure, clarifies the essential multidirectional and systemic nature of genomic information transfer, and emphasizes the need to investigate how cellular computation operates in reproduction and evolution. (shrink)

In this review, we discuss how two evolutionarily conserved pathways at the interface of DNA replication and repair, template switching and break-induced replication, lead to the deleterious large-scale expansion of trinucleotide DNA repeats that cause numerous hereditary diseases. We highlight that these pathways, which originated in prokaryotes, may be subsequently hijacked to maintain long DNA microsatellites in eukaryotes. We suggest that the negative mutagenic outcomes of these pathways, exemplified by repeat expansion diseases, are likely outweighed by their positive role in (...) maintaining functional repetitive regions of the genome such as telomeres and centromeres. Break-induced replication and template switching are conserved mechanisms of replication fork restart. They do not cause microsatellite instability in prokaryotes, but promote repeat expansion in eukaryotes. We suggest that TS and BIR persisted in eukaryotes despite their mutagenic potential because they help maintain long repetitive telomeres and centromeres. (shrink)

The presence of small polydisperse extrachromosomal circular (spc) DNAs composed entirely of chromosomal sequences seems to reflect the plasticity of eukaryotic genomes. The size distribution and number of spc DNAs is found to vary with development, growth state and mitotic capacity. In particular, spc DNAs are observed to be several fold smaller in established immortal cell lines than in diploid cells with a limited life span. Analysis of cloned spc DNA fragments revealed that: (1) most of the spc DNAs thus (...) far investigated contain repetitive sequences; (2) some of the repetitive sequences are enriched in spc DNA clones relative to their representation in the chromosome; (3) various repetitive sequences of different reiteration frequency were found in spc DNA from immortal cell lines while a particular sequence of retroposon was predominant in primary lymphoid tissue cells and stem cells; (4) most of these spc DNAs appear to represent the extra copies generated by replicon‐misfiring in immortal cell lines or by retrotranscription in stem cells, and intermediates or by‐products produced by abortive rearrangement in diploid cells with a finite replicative capacity. (shrink)

DNA helicases are a class of molecular motors that catalyze processive unwinding of double stranded DNA. In spite of much study, we know relatively little about the mechanisms by which these enzymes carry out the function for which they are named. Most current views are based on inferences from crystal structures. A prominent view is that the canonical ATPase motor exerts a force on the ssDNA resulting in “pulling” the duplex across a “pin” or “wedge” in the enzyme leading to (...) a mechanical separation of the two DNA strands. In such models, DNA base pair separation is tightly coupled to ssDNA translocation of the motors. However, recent studies of the Escherichia coli RecBCD helicase suggest an alternative model in which DNA base pair melting and ssDNA translocation occur separately. In this view, the enzyme‐DNA binding free energy is used to melt multiple DNA base pairs in an ATP‐independent manner, followed by ATP‐dependent translocation of the canonical motors along the newly formed ssDNA tracks. Repetition of these two steps results in processive DNA unwinding. We summarize recent evidence suggesting this mechanism for RecBCD helicase action. (shrink)

The genomes of the slime moulds are relatively small when compared with those of higher eukaryotes. They also contain far fewer families of repetitive sequences. Nevertheless, the general patterns of organization of their repetitive DNA are similar. The slime moulds can therefore help us to investigate the structure and evolution of repetitive DNA in “simple” eukaryotes and to understand how these sequences contribute to the architecture and function of the eukaryotic genome. Several questions remain, including perhaps the (...) most important: do repetitive sequences perform some definable function?. (shrink)

The recent publication by Wylie et al. is reviewed, demonstrating that the p53 protein regulates the movement of transposons. While this work presents genetic evidence for a piRNA‐mediated p53 interaction with transposons in Drosophila and zebrafish, it is herein placed in the context of a decade or so of additional work that demonstrated a role for p53 in regulating transposons and other repetitive elements. The line of thought in those studies began with the observation that transposons damage DNA and (...) p53 regulates DNA damage. The presence of transposon movement can increase the rate of evolution in the germ line and alter genes involved in signal transduction pathways. Transposition can also play an important role in cancers where the p53 gene function is often mutated. This is particularly interesting as recent work has shown that de‐repression of repetitive elements in cancer has important consequences for the immune system and tumor microenvironment. (shrink)

A diploid human genome contains approximately six billion nucleotides. This enormous amount of genetic information can be replicated with great accuracy in only a few hours. However, because DNA strands are oriented antiparallel while DNA polymerization only occurs in the 5′ → 3′ direction, semi‐conservative replication of double‐stranded DNA is an asymmetric process, i.e., there is a leading and a lagging strand. This provides a considerable opportunity for non‐random error rates, because the architecture of the two strands as well as (...) the DNA polymerases that replicate them may be different. In addition, the proteins that start or finish chains may well be different from those that perform the bulk of chain elongation. Furthermore, while replication fidelity depends on the absolute and relative concentrations of the four deoxyribonucleotide precursors, these are not equal in vivo, not constant throughout the cell cycle, and not necessarily equivalent in all cell types. Finally, the fidelity of DNA synthesis is sequence‐dependent and the eukaryotic nuclear genome is a heterogeneous substrate. It contains repetitive and non‐repetitive sequences and can actually be considered as two subgenomes that differ in nucleotide composition and gene content and that replicate at different times. The effects that each of these asymmetries may have on error rates during replication of the eukaryotic genome are discussed. (shrink)

The replicative bypass of lesions in DNA and the induction of mutations by agents which react with DNA to produce damaged bases can be understood on the basis of a simple kinetic model. Bypass can be analyzed by separately considering three processes: (a) addition of a base opposite a lesion, (b) a proofreading excision process, and (c) a rate limiting elongation step. Adenine nucleotides are preferentially added opposite many lesions making it possible to predict mutational specificity. Replicative bypass (translesion synthesis) (...) is dependent on modulation of proofreading exonuclease activity but loss of exonuclease activity alone is not sufficient to ensure bypass. Frameshift mutation is the result of the failure of translesion synthesis accompanied by rearrangement of the template, particularly at repetitive sites. (shrink)

In spite of the importance of point mutations for evolution and human diseases, their natural spectrum of incidence in different species is not known. Here I propose to determine these spectra by comparing consecutive sequence periods in stretches of repetitive DNA. The article presents the analysis of more than 51,000 such point mutations identified by this approach in the genomes of human, chimpanzee, rat, mouse, pufferfish, zebrafish, and sea squirt. I propose to explain the observed spectra by auto‐mutagenic mechanisms (...) of genome variation involving the inter‐conversions of nucleotides, single base‐pair inversions and their combinations. (shrink)

The placenta invades the adjacent uterus and controls the maternal immune system, like a cancer invades surrounding organs and suppresses the local immune response. Intriguingly, placental and cancer cells are globally hypomethylated and share an epigenetic phenomenon that is not well understood – they fail to silence repetitive DNA sequences that are silenced in healthy somatic cells. In the placenta, hypomethylation of retrotransposons has facilitated the evolution of new genes essential for placental function. In cancer, hypomethylation is thought to (...) contribute to activation of oncogenes, genomic instability, and retrotransposon unsilencing; the latter, we postulate, is possibly the most important consequence. Activation of placental retrotransposon-derived genes in cancer underpins our hypothesis that hypomethylation of these genes drives cancer cell invasion. This alludes to an interesting paradox, that while placental retrotransposon-derived genes are essential for promoting early hominid life, the same genes promote disease-susceptibility and death through cancer. Placental and cancer cells fail to silence retrotransposons that are normally silenced in healthy tissues. This has created new genes that are essential for placental function, yet they are also expressed in cancer. We hypothesize that active retrotransposons are a double-edged sword, contributing both adaptive and deleterious functions to biology. (shrink)

Telomeres are short repetitive DNA sequences capping the ends of chromosomes. Telomere shortening occurs during cell division and may be accelerated by oxidative damage or ameliorated by telomere maintenance mechanisms. Consequently, telomere length changes with age, which was recently confirmed in a large meta‐analysis across vertebrates. However, based on the correlation between telomere length and age, it was concluded that telomere length can be used as a tool for chronological age estimation in animals. Correlation should not be confused with (...) predictability, and the current data and studies suggest that telomeres cannot be used to reliably predict individual chronological age. There are biological reasons for why there is large individual variation in telomere dynamics, which is mainly due to high susceptibility to a wide range of environmental, but also genetic factors, rendering telomeres unfeasible as a tool for age estimation. The use of telomeres for chronological age estimation is largely a misguided effort, but its occasional reappearance in the literature raises concerns that it will mislead resources in wildlife conservation. (shrink)

Horizontal transfer (HT) is the transmission of genetic material between non‐mating species, a phenomenon thought to occur rarely in multicellular eukaryotes. However, many transposable elements (TEs) are not only capable of HT, but have frequently jumped between widely divergent species. Here we review and integrate reported cases of HT in retrotransposons of the BovB family, and DNA transposons, over a broad range of animals spanning all continents. Our conclusions challenge the paradigm that HT in vertebrates is restricted to infective long (...) terminal repeat (LTR) retrotransposons or retroviruses. This raises the possibility that other non‐LTR retrotransposons, such as L1 or CR1 elements, believed to be only vertically transmitted, can horizontally transfer between species. Growing evidence indicates that the process of HT is much more general across different TEs and species than previously believed, and that it likely shapes eukaryotic genomes and catalyses genome evolution. (shrink)

It is becoming increasingly evident that the driving forces of evolutionary novelty are not randomly derived chance mutations of the genetic text, but a precise genome editing by omnipresent viral agents. These competences integrate the whole toolbox of natural genetic engineering, replication, transcription, translation, genomic imprinting, genomic creativity, enzymatic inventions and all types of genetic repair patterns. Even the non-coding, repetitive DNA sequences which were interpreted as being ancient remnants of former evolutionary stages are now recognized as being of (...) viral descent and crucial for higher-order regulatory and constitutional functions of protein structural vocabulary. In this article I argue that non-randomly derived natural genome editing can be envisioned as (a) combinatorial (syntactic), (b) context-specific (pragmatic) and (c) content-sensitive (semantic) competences of viral agents. These three-leveled biosemiotic competences could explain the emergence of complex new phenotypes in single evolutionary events. After short descriptions of the non-coding regulatory networks, major viral life strategies and pre-cellular viral life three of the major steps in evolution serve as examples: There is growing evidence that natural genome-editing competences of viruses are essential (1) for the evolution of the eukaryotic nucleus, (2) the adaptive immune system and (3) the placental mammals. (shrink)

Dawkins in his The Selfish Gene(1) quite aptly applies the term “selfish” to parasitic repetitive DNA sequences endemic to eukaryotic genomes, especially vertebrates. Doolittle and Sapienza(2) as well as Orgel and Crick(3) enlivened this notion of selfish DNA with the identification of such repetitive sequences as remnants of mobile elements such as transposons. In addition, Orgel and Crick(3) associated parasitic DNA with a potential to outgrow their host genomes by propagating both vertically via conventional genome replication as well (...) as infectiously by horizontal gene transfer (HGT) to other genomes. Still later, Doolittle(4) speculated that unchecked HGT between unrelated genomes so complicates phylogeny that the conventional representation of a tree of life would have to be replaced by a thicket or a web of life.(4) In contrast, considerable data now show that reconstructions based on whole genome sequences are consistent with the conventional “tree of life”.(5–10) Here, we identify natural barriers that protect modern genome populations from the inroads of rampant HGT. BioEssays 27:741–747, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

It is becoming increasingly clear that repetitive DNA is of biological significance as well as experimental importance. Here we review the information available about one type of repetitive DNA, the trinucleotide repeat (CAC)n, and briefly compare it with other trinucleotide repeats. Although much work has been done in analysing DNA fingerprinting patterns produced using the synthetic oligonucleotide (CAC)5 as a probe, there is relatively little information about individual (CAC)n‐containing sequences and their abundance, organisation and distribution in mammalian DNA. (...) From the data that is available, it is clear that there are at least two areas that should repay further study: (1) the organisation and generation of long sequences that contain (CAC)n motifs as part of a larger repeating unit (minisatellites) and (2) the distribution of small (CAC)n sequences (microsatellites), in particular their relationship to genes. (shrink)

DNA repetitions may provoke heterochromatinization. We explore here a model in which multiple cis‐acting sequences that display no silencing activity on their own (protosilencers) may cooperate to establish and maintain a heterochromatin domain efficiently. Protosilencers, first defined in budding yeast, have now been found in a wide range of genomes where they appear to stabilize and to extend the propagation of heterochromatin domains. Strikingly, isolated or moderately repeated protosilencers can also be found in promoters where they participate in transcriptional activation (...) and have insulation functions. This suggests that the proper juxtaposition of a threshold number of protosilencers converts them from neutral or transactivating elements into ones that nucleate heterochromatin. Interactions might be transient or permanent, and are likely to occur over distances by looping. This model provides a conceptual framework for as varied phenomena as telomere‐driven silencing in Drosophila, X inactivation in mammals, and rDNA silencing in S. cerevisiae. It may also account for the silencing that occurs when multiple copies of a transgene are inserted in tandem. BioEssays 24:828–835, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

Short interspersed repetitive elements, or SINEs, are tRNA-derived retroposons that are dispersed throughout eukaryotic genomes and can be present in well over 104 total copies. The enormous volume of SINE amplifications per organism makes them important evolutionary agents for shaping the diversity of genomes, and the irreversible, independent nature of their insertion allows them to be used for diagnosing common ancestry among host taxa with extreme confidence. As such, they represent a powerful new tool for systematic biology that can (...) be strategically integrated with other conventional phylogenetic characters, most notably morphology and DNA sequences. This review covers the basic aspects of SINE evolution that are especially relevant to their use as systematic characters and describes the practical methods of characterizing SINEs for cladogram construction. It also discusses the limits of their systematic utility, clarifies some recently published misunderstandings, and illustrates the effective application of SINEs for vertebrate phylogenetics with results from selected case studies. BioEssays 22:148–160, 2000. ©2000 John Wiley & Sons, Inc. (shrink)

The classical view of the gene prevailing during the 1910s and 1930s comprehended the gene as the indivisible unit of genetic transmission, genetic recombination, gene mutation and gene function. The discovery of intragenic recombination in the early 1940s led to the neoclassical concept of the gene, which prevailed until the 1970s. In this view the gene or cistron, as it was now called, was divided into its constituent parts, the mutons and recons, materially identified as nucleotides. Each cistron was believed (...) to be responsible for the synthesis of one single mRNA and concurrently for one single polypeptide. The discoveries of DNA technology, beginning in the early 1970s, have led to the second revolution in the concept of the gene in which none of the classical or neoclassical criteria for the definition of the gene hold strictly true. These are the discoveries concerning gene repetition and overlapping, movable genes, complex promoters, multiple polyadenylation sites, polyprotein genes, editing of the primary transcript, pseudogenes and gene nesting. Thus, despite the fact that our comprehension of the structure and organization of the genetic material has greatly increased, we are left with a rather , open and general concept of the gene. This article discusses past and present contemplations of genes, genomes, genotypes and phenotypes as well as the most recent advances of the study of the organization of genomes. (shrink)

The orderly sequence of events that constitutes the cell cycle is carefully regulated. A part of this regulation depends upon the ubiquitous calcium signalling system. Many growth factors utilize the messenger inositol trisphosphate (InsP3) to set up prolonged calcium signals, often organized in an oscillatory pattern. These repetitive calcium spikes require both the entry of external calcium and its release from internal stores. One function of this calcium signal is to activate the immediate early genes responsible for inducing resting (...) cells (G0) to re‐enter the cell cycle. It may also promote the initiation of DNA synthesis at the G1/S transition. Finally, calcium contributes to the completion of the cell cycle by stimulating events at mitosis. The role of calcium in cell proliferation is highlighted by the increasing number of anticancer therapies and immunosuppressant drugs directed towards this calcium signalling pathway. (shrink)

Two reports have shown that mammalian artificial chromosomes (MAC) can be constructed from cloned human centromere DNA and telomere repeats, proving the principle that chromosomes can form from naked DNA molecules transfected into human cells. The MACs were mitotically stable, low copy number and bound antibodies associated with active centromeres. As a step toward second-generation MACs, yeast and bacterial cloning systems will have to be adapted to achieve large MAC constructs having a centromere, two telomeres, and genomic copies of mammalian (...) genes. Available construction techniques are discussed along with a new P1 artificial chromosome (PAC)-derived telomere vector (pTAT) that can be joined to other PACs in vitro, avoiding a cloning step during which large repetitive arrays often rearrange. The PAC system can be used as a route to further define the optimal DNA elements required for efficient MAC formation, to investigate the expression of genes on MACs, and possibly to develop efficient MAC-delivery protocols. BioEssays 1999;21:76–83. © 1999 John Wiley & Sons, Inc. (shrink)

Two reports have shown that mammalian artificial chromosomes (MAC) can be constructed from cloned human centromere DNA and telomere repeats, proving the principle that chromosomes can form from naked DNA molecules transfected into human cells. The MACs were mitotically stable, low copy number and bound antibodies associated with active centromeres. As a step toward second-generation MACs, yeast and bacterial cloning systems will have to be adapted to achieve large MAC constructs having a centromere, two telomeres, and genomic copies of mammalian (...) genes. Available construction techniques are discussed along with a new P1 artificial chromosome (PAC)-derived telomere vector (pTAT) that can be joined to other PACs in vitro, avoiding a cloning step during which large repetitive arrays often rearrange. The PAC system can be used as a route to further define the optimal DNA elements required for efficient MAC formation, to investigate the expression of genes on MACs, and possibly to develop efficient MAC-delivery protocols. BioEssays 1999;21:76–83. © 1999 John Wiley & Sons, Inc. (shrink)

Mammalian cells frequently depend on homologous recombination (HR) to repair DNA damage accurately and to help rescue stalled or collapsed replication forks. The essence of HR is an exchange of nucleotides between identical or nearly identical sequences. Although HR fulfills important biological roles, recombination between inappropriate sequence partners can lead to translocations or other deleterious rearrangements and such events must be avoided. For example, the recombination machinery must follow stringent rules to preclude recombination between the many repetitive elements in (...) a mammalian genome that share significant but imperfect homology. This paper takes a conceptual approach in addressing the homology requirements for recombination in mammalian genomes as well as the general strategy used by cells to reject recombination between similar but imperfectly matched sequences. A mechanism of heteroduplex rejection that involves the unwinding of recombination intermediates that may form between mismatched sequences is discussed. BioEssays 30:1163–1171, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Telomerase is a cellular reverse transcriptase responsible for telomere maintenance in most organisms. It does so by adding telomere repeats onto pre‐existing ends using an integral RNA component as template. Compared to “prototypical” reverse transcriptases, telomerase is unique in being able to repetitively copy a short templating RNA segment, thus adding multiple copies of the repeat to the DNA substrate following a single binding event. This uniquely processive property hints at the intricate conformational alterations that the enzyme must choreograph during (...) its reaction cycles. Recent studies have identified distinct structural elements within both the RNA and protein components of telomerase that modulate enzyme processivity. Pharmacological and genetic analysis suggest that telomerase processivity is a significant determinant of telomere length. Because telomere maintenance and the lack thereof have been linked to tumor progression and aging, further investigation of telomerase processivity may lead to novel medical intervention strategies. BioEssays 26:955–962, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Parental age at offspring conception often influences offspring longevity, but the mechanisms underlying this link are poorly understood. One mechanism that may be important is telomeres, highly conserved, repetitive sections of non‐coding DNA that form protective caps at chromosome ends and are often positively associated with longevity. Here, the potential pathways by which the age of the parents at the time of conception may impact offspring telomeres are described first, including direct effects on parental gamete telomeres and indirect effects (...) on offspring telomere loss during pre‐ or post‐natal development. Then a surge of recent studies demonstrating the effects of parental age on offspring telomeres in diverse taxa are reviewed. In doing so, important areas for future research and experimental approaches that will enhance the understanding of how and when these effects likely occur are highlighted. It is concluded by considering the potential evolutionary consequences of parental age on offspring telomeres. (shrink)

Of fundamental importance to literary critics and philosophers, Difference and Repetition develops two central concepts -- pure difference and complex ...

In the second lecture of "Naming and Necessity," Saul Kripke presented a new and quite convincing picture of the reference of proper names. At the same time, however, he expressed some skepticism towards the possibility of developing it into a full-blown theory by offering “more exact conditions for reference to take place.” In this paper, after discussing the reasons for his skepticism, I hint at how I think Kripke’s picture could be developed and offer an outline of a theory of (...) reference based on it. One of the key notions my ‘theory’ makes use of is that of repetition, which I take from Kaplan’s “Words.”. (shrink)

This brilliant exposition of the critique of identity is a classic in contemporary philosophy and one of Deleuze's most important works. Of fundamental importance to literary critics and philosophers,Difference and Repetition develops two central concepts—pure difference and complex repetition&mdasha;and shows how the two concepts are related. While difference implies divergence and decentering, repetition is associated with displacement and disguising. Central in initiating the shift in French thought away from Hegel and Marx toward Nietzsche and Freud, _Difference and Repetition_ moves deftly (...) to establish a fundamental critique of Western metaphysics. (shrink)

This Christian sermon uses a DNA lab experience as a basis for theological reflection on ourselves and our offering. Who are we to God? What determines the self that we offer? Can the alphabet of DNA shed light for us on the Word of God in our lives? This first attempt to introduce the language and laboratory environment of genetic testing (represented by DNA fingerprinting) within a parish preaching context juxtaposes liturgical, scientific, and biblical language and settings for fresh insights.

DNA methylation can be considered a component of epigenetic memory with a critical role during embryo development, and which undergoes dramatic reprogramming after fertilization. Though it has been a focus of research for many years, the reprogramming mechanism is still not fully understood. Recent results suggest that absence of maintenance at DNA replication is a major factor, and that there is an unexpected role for TET3-mediated oxidation of 5mC to 5hmC in guarding against de novo methylation. Base-resolution and genome-wide profiling (...) methods are enabling more comprehensive assessments of the extent to which ART might impair DNA methylation reprogramming, and which sequence elements are most vulnerable. Indeed, as we also review here, studies showing the effect of culture media, ovarian stimulation or embryo transfer on the methylation pattern of embryos emphasize the need to face ART-associated defects and search for strategies to mitigate adverse effects on the health of ART-derived children. DNA methylation, critical for embryo development, suffers significant changes after fertilization, including demethylation, remethylation and TET3-mediated oxidation of 5 mC to 5 hmC. In addition to infertility and environmental insults, ART could impact DNA methylation and ART related consequences in the offspring have been reported. (shrink)

The pedagogical function of science teaching may benefit from an analysis of the historical-epistemic dimension, without neglecting the socio-political context in which a given research was carried out. In the case of DNA structure, the background of its discovery is particularly complex. Starting from the analysis of some papers, the view on the circumstances that led to their drafting broadens. We try to answer the fundamental question for any educator: why teach all that? Ethics issues are related to the general (...) organisation of research, increasingly focused on speed and competition. Even teaching is affected by these dynamics, not only in higher education, but also at secondary level; students should be made aware of this trend. The history of science could therefore favour a more general awareness. _SUNTO_ La funzione pedagogica dell’insegnamento scientifico può trarre vantaggio da un’analisi della dimensione storico-epistemica, senza trascurare il contesto socio-politico nel quale una determinata ricerca è stata condotta. Nel caso della struttura del DNA, i retroscena della sua scoperta sono particolarmente complessi. Dopo l’analisi di alcuni articoli, si allarga gradualmente la vista sulle circostanze che hanno condotto alla loro stesura. Si cerca di rispondere a una domanda fondamentale per ogni educatore: perché insegnare tutto ciò? Le questioni etiche riguardano l’organizzazione generale della ricerca, sempre più tesa alla velocità e alla competizione. Persino l’insegnamento è influenzato da dinamiche simili, non solo in ambito accademico, ma anche a livello secondario; gli studenti dovrebbero essere a conoscenza di questa tendenza. La storia della scienza può dunque favorire una maggiore consapevolezza. (shrink)

DNA topoisomerases, capable of manipulating DNA topology, are ubiquitous and indispensable for cellular survival due to the numerous roles they play during DNA metabolism. As we review here, current structural approaches have revealed unprecedented insights into the complex DNA‐topoisomerase interaction and strand passage mechanism, helping to advance our understanding of their activities in vivo. This has been complemented by single‐molecule techniques, which have facilitated the detailed dissection of the various topoisomerase reactions. Recent work has also revealed the importance of topoisomerase (...) interactions with accessory proteins and other DNA‐associated proteins, supporting the idea that they often function as part of multi‐enzyme assemblies in vivo. In addition, novel topoisomerases have been identified and explored, such as topo VIII and Mini‐A. These new findings are advancing our understanding of DNA‐related processes and the vital functions topos fulfil, demonstrating their indispensability in virtually every aspect of DNA metabolism. (shrink)

This paper focuses on the question of whether DNA patents help or hinder scientific discovery and innovation. While DNA patents create a wide variety of possible benefits and harms for science and technology, the evidence we have at this point in time supports the conclusion that they will probably promote rather than hamper scientific discovery and innovation. However, since DNA patenting is a relatively recent phenomena and the biotechnology industry is in its infancy, we should continue to gather evidence about (...) the effects of DNA patenting on scientific innovation and discovery as well the economic, social, and legal conditions relating to intellectual property in biotechnology. We should give the free market, the courts, researchers, and patent offices a chance to settle issues related to innovation and discovery, before we seek legislative remedies, since new laws proposed at this point would lack adequate foresight and could do more harm than good. However, we should be open to new laws or regulations on DNA patents if they are required to in order to deal with some of the biases and limitations of the free market. (shrink)

This article analyses the parallels between the pre-Qin Daoist notion of heng 恒 as a constancy that is nevertheless ceaselessly in motion, and Karl Barth’s concept of Beständigkeit as God’s constancy throughout infinite transformation. Underlying both concepts is an understanding of the ultimate origin (whether dao 道or the Christian God) as irreducibly temporal in nature. Stemming from this conviction, both systems of thought ultimately identify the continuous change of the ultimate origin with the flow of time in the universe. The (...) commonalities found between these two traditions provide fresh resources to advance the study of both. On the one hand, Barth’s deliberate juxtaposition of contrary statements to illustrate the union of permanence and transience in Beständigkeit challenges the frequent assumption that similar juxtapositions in the pre-Qin texts comprise careless inconsistency or outright incoherence. By extension, Barth’s metaphysical underpinning of this juxtaposition offers a compelling framework to explicate the Daoist notion of heng. On the other hand, the pre-Qin texts’ confluence of permanence and freedom in the principle of ziran 自然 offers a new lens through which to read and hence redeem Barth’s oft-critiqued attempt to combine the irrevocability and ongoing freedom of God’s decision of election. (shrink)

DNA methylation is a repressive epigenetic mark vital for normal development. Recent studies have uncovered an unexpected role for the DNA methylome in ensuring the correct targeting of the Polycomb repressive complexes throughout the genome. Here, we discuss the implications of these findings for cancer, where DNA methylation patterns are widely reprogrammed. We speculate that cancer‐associated reprogramming of the DNA methylome leads to an altered Polycomb binding landscape, influencing gene expression by multiple modes. As the Polycomb system is responsible for (...) the regulation of genes with key roles in cell fate decisions and cell cycle regulation, DNA methylation induced Polycomb mis‐targeting could directly drive carcinogenesis and disease progression.Editor's suggested further reading in BioEssays Unmasking risk loci: DNA methylation illuminates the biology of cancer predisposition Abstract. (shrink)

Type II DNA topoisomerase activity is required to change DNA topology. It is important in the relaxation of DNA supercoils generated by cellular processes, such as transcription and replication, and it is essential for the condensation of chromosomes and their segregation during mitosis. In mammals this activity is derived from at least two isoforms, termed DNA topoisomerase IIα and β. The α isoform is involved in chromosome condensation and segregation, whereas the role of the β isoform is not yet clear. (...) DNA topoisomerase IIβ was first reported in 1987. Here we review the research on DNA topoisomerase IIβ over the last 10 years. BioEssays 20:215–226, 1998.© 1998 John Wiley & Sons, Inc. (shrink)

Those objecting to human DNA patenting frequently do so on the grounds that the practice violates or threatens human dignity. For example, from 1993 to 1994, more than thirty organizations representing indigenous peoples approved formal declarations objecting to the National Institutes of Health's bid to patent viral DNA taken from subjects in Papua New Guinea and the Solomon Islands. Although these were not patents on human DNA, the organizations argued that the patents could harm and exploit indigenous peoples and violate (...) their cultural values. NIH eventually dropped one of its patent applications.On May 18, 1995, 180 religious leaders, led by biotechnology critic Jeremy Rifkin, held a press conference objecting to DNA patenting in Washington, D.C. In their “Joint Appeal against Human and Animal Patenting,” these leaders decried any attempt to patent nature. Some of the more outspoken members of the Joint Appeal likened DNA patenting to slavery, while others objected to treating human beings as marketable commodities. In his recent book, The Biotech Century, Rifkin rehashed the objections to DNA patenting voiced by members of the Joint Appeal. (shrink)

The regulation of DNA replication is a fascinating biological problem both from a mechanistic angle—How is replication timing regulated?—and from an evolutionary one—Why is replication timing regulated? Recent work has provided significant insight into the first question. Detailed biochemical understanding of the mechanism and regulation of replication initiation has made possible robust hypotheses for how replication timing is regulated. Moreover, technical progress, including high‐throughput, single‐molecule mapping of replication initiation and single‐cell assays of replication timing, has allowed for direct testing of (...) these hypotheses in mammalian cells. This work has consolidated the conclusion that differential replication timing is a consequence of the varying probability of replication origin initiation. The second question is more difficult to directly address experimentally. Nonetheless, plausible hypotheses can be made and one—that replication timing contributes to the regulation of chromatin structure—has received new experimental support. (shrink)

The nuclear pore complex (NPC) is emerging as a center for recruitment of a class of “difficult to repair” lesions such as double‐strand breaks without a repair template and eroded telomeres in telomerase‐deficient cells. In addition to such pathological situations, a recent study by Su and colleagues shows that also physiological threats to genome integrity such as DNA secondary structure‐forming triplet repeat sequences relocalize to the NPC during DNA replication. Mutants that fail to reposition the triplet repeat locus to the (...) NPC cause repeat instability. Here, we review the types of DNA lesions that relocalize to the NPC, the putative mechanisms of relocalization, and the types of recombinational repair that are stimulated by the NPC, and present a model for NPC‐facilitated repair. (shrink)

Through analysis of film sequences focusing on DNA in two British Broadcasting Corporation nonfiction science television programs, Wonders of Life and Bang! Goes the Theory, first broadcast in 2013, contrasting “religious” and “secular” representations of science are identified. In the “religious” portrayal, immutable scientific knowledge is revealed to humanity by nature with minimal human intervention. Science provides a creation story, “explanatory omnicompetence,” and makes life existentially meaningful. In the “secular” portrayal, scientific knowledge is changeable; is produced through technical skill in (...) expert communities; and is ambiguous, potentially positive and negative for society. Television representations of science affect audience understandings, and this is particularly the case for nonfiction representations of science, as they are likely to be “taken more seriously” than fictional representations. The consequences of the “religious” representation of science are discussed, and it is argued that a widespread understanding of science as presented in the religious portrayal would negatively impact democracy. (shrink)

Over 30 million people worldwide have taken a commercial at-home DNA test, because they were interested in their genetic ancestry, disease predisposition or inherited traits. Yet, these consumer DNA data are also increasingly used for a very different purpose: to identify suspects in criminal investigations. By matching a suspect’s DNA with DNA from a suspect’s distant relatives who have taken a commercial at-home DNA test, law enforcement can zero in on a perpetrator. Such forensic use of consumer DNA data has (...) been performed in over 200 criminal investigations. However, this practice of so-called investigative genetic genealogy raises ethical concerns. In this paper, we aim to broaden the bioethical analysis on IGG by showing the limitations of an individual-based model. We discuss two concerns central in the debate: privacy and informed consent. However, we argue that IGG raises pressing ethical concerns that extend beyond these individual-focused issues. The very nature of the genetic information entails that relatives may also be affected by the individual customer’s choices. In this respect, we explore to what extent the ethical approach in the biomedical genetic context on consent and consequences for relatives can be helpful for the debate on IGG. We argue that an individual-based model has significant limitations in an IGG context. The ethical debate is further complicated by the international, transgenerational and commercial nature of IGG. We conclude that IGG should not only be approached as an individual but also—and perhaps primarily—as a collective issue. There are no data in this work. (shrink)

Science; Ethics; Politics; Beyond recombinant dna.

DNA barcodes, like traditional sources of taxonomic information, are potentially powerful heuristics in the identification of described species but require mindful analytical interpretation. The role of DNA barcoding in generating hypotheses of new taxa in need of formal taxonomic treatment is discussed, and it is emphasized that the recursive process of character evaluation is both necessary and best served by understanding the empirical mechanics of the discovery process. These undertakings carry enormous ramifications not only for the translation of DNA sequence (...) data into taxonomic information but also for our comprehension of the magnitude of species diversity and its disappearance. This paper examines the potential strengths and pitfalls of integrating DNA sequence data, specifically in the form of DNA barcodes as they are currently generated and analyzed, with taxonomic practice. (shrink)

From the Tin Pan Alley 32-bar form, through the cyclical forms of modal jazz, to the more recent accumulation of digital layers, beats, and breaks in Electronic Dance Music, repetition as both an aesthetic disposition and a formal property has stimulated a diverse range of genres and techniques. From the angles of musicology, psychology, sociology, and science and technology, Over and Over reassesses the complexity connected to notions of repetition in a variety of musical genres. The first edited volume on (...) repetition in 20th- and 21st-century popular music, Over and Over explores the wide-ranging forms and use of repetition - from large repetitive structures to micro repetitions - in relation to both specific and large-scale issues and contexts. The book brings together a selection of original texts by leading authors in a field that is, as yet, little explored. Aimed at both specialists and neophytes, it sheds important new light on one of the fundamental phenomena of music of our times. (shrink)

Using research into learning from sequences of examples, we generate predictions about what cultural products become widely distributed in the social marketplace of ideas. We investigate what we term the Repetition‐Break plot structure: the use of repetition among obviously similar items to establish a pattern, and then a final contrasting item that breaks with the pattern to generate surprise. Two corpus studies show that this structure arises in about a third of folktales and story jokes. An experiment shows that jokes (...) with this structure are more interesting than those without the initial repetition. Thus, we document evidence for how a cognitive factor influences the cultural products that are selected in the marketplace of ideas. (shrink)