The distinction between causal role and selected effect functions is typically framed in terms of their respective explanatory roles. However, much of the controversy over functions in genomics takes place in an investigative, not an explanatory context. Specifically, the process of component-driven functional investigation begins with the designation of some genetic or epigenetic element as functional —i.e. not junk— because it possesses properties that, arguably, suggest some biologically interesting organismal effect. The investigative process then proceeds, in a bottom-up fashion, (...) to search for those effects. I argue that this process encounters a problem reminiscent of one that Gould and Lewontin associated with the adaptationist program. Just as their stereotypical adaptationst became trapped in the myopic pursuit of one selectionist hypothesis after another, so can the investigation of CR functions in genomics lead to an unending series putative organism-level CR functions for junk DNA. This is an acute problem for genomics, because eukaryotic genomes are littered with transposable elements and their deactivated descendants which often masquerade as interesting CR-functional components and it is experimentally onerous to determine whether they lack such a function. I further argue that selectionist reasoning about TE-host coevolutionary dynamics can greatly streamline the investigative process. Importantly, selectionist hypotheses need not be well confirmed to be illuminating in this context. Informed selectionist reasoning about the strategic roles of TEs in the genome offers a corrective to the idea that most of our DNA is somehow CR functional for the organism. (shrink)

In its last round of publications in September 2012, the Encyclopedia Of DNA Elements (ENCODE) assigned a biochemical function to most of the human genome, which was taken up by the media as meaning the end of ‘Junk DNA’. This provoked a heated reaction from evolutionary biologists, who among other things claimed that ENCODE adopted a wrong and much too inclusive notion of function, making its dismissal of junk DNA merely rhetorical. We argue that this criticism rests on (...) misunderstandings concerning the nature of the ENCODE project, the relevant notion of function and the claim that most of our genome is junk. We argue that evolutionary accounts of function presuppose functions as ‘causal roles’, and that selection is but a useful proxy for relevant functions, which might well be unsuitable to biomedical research. Taking a closer look at the discovery process in which ENCODE participates, we argue that ENCODE’s strategy of biochemical signatures successfully identified activities of DNA elements with an eye towards causal roles of interest to biomedical research. We argue that ENCODE’s controversial claim of functionality should be interpreted as saying that 80 % of the genome is engaging in relevant biochemical activities and is very likely to have a causal role in phenomena deemed relevant to biomedical research. Finally, we discuss ambiguities in the meaning of junk DNA and in one of the main arguments raised for its prevalence, and we evaluate the impact of ENCODE’s results on the claim that most of our genome is junk. (shrink)

It is often thought that non-junk or coding DNA is more significant than other cellular elements, including so-called junk DNA. This is for two main reasons: because coding DNA is often targeted by historical or current selection, it is considered functionally special and because its mode of action is uniquely specific amongst the other actual difference makers in the cell, it is considered causally special. Here, we challenge both these presumptions. With respect to function, we argue that there (...) is previously unappreciated reason to think that junk DNA is significant, since it can alter the cellular environment, and those alterations can influence how organism-level selection operates. With respect to causality, we argue that there is again reason to think that junk DNA is significant, since it too is remarkably causally specific. As a result, something is missing from the received view of significance in molecular biology—a view which emphasizes specificity and neglects something we term ‘reach’. With the special case of junk DNA in mind, we explore how to model and understand the causal specificity, reach, and corresponding efficacy of difference makers in biology. The account contains implications for how evolution shapes the genome, as well as advances our understanding of multi-level selection. (shrink)

Autonomous transposable elements, generally considered as junk and selfish, encode transposition proteins that can bind, copy, break, join or degrade nucleic acids as well as process or interact with other proteins. Such a repertoire of activities might be of interest for the host cell. There is indeed substantial evidence that mobile DNA can serve as a dynamic reservoir for new cellular functions. Transposable element genes encoding transposase, integrase, reverse transcriptase as well as structural and envelope proteins have been repeatedly (...) recruited by their host during evolution in most eukaryotic lineages. Such domesticated sequences protect us against infections, are necessary for our reproduction, allow the replication of our chromosomes and control cell proliferation and death; others are essential for plant development. Many new candidates for domesticated sequences have been revealed by sequencing projects. Their functional analysis will uncover new aspects of evolutionary alchemy, the turning of junk into gold within genomes. BioEssays 28: 913–922, 2006. © 2006 Wiley periodicals, Inc. (shrink)

Recent investigations have revealed 1) that the isochores of the human genome group into two super‐families characterized by two different long‐range 3D structures, and 2) that these structures, essentially based on the distribution and topology of short sequences, mold primary chromatin domains (and define nucleosome binding). More specifically, GC‐poor, gene‐poor isochores are low‐heterogeneity sequences with oligo‐A spikes that mold the lamina‐associated domains (LADs), whereas GC‐rich, gene‐rich isochores are characterized by single or multiple GC peaks that mold the topologically associating domains (...) (TADs). The formation of these “primary TADs” may be followed by extrusion under the action of cohesin and CTCF. Finally, the genomic code, which is responsible for the pervasive encoding and molding of primary chromatin domains (LADs and primary TADs, namely the “gene spaces”/“spatial compartments”) resolves the longstanding problems of “non‐coding DNA,” “junk DNA,” and “selfish DNA” leading to a new vision of the genome as shaped by DNA sequences. (shrink)

The human genome project's lasting legacies are the emerging insights into human physiology and disease, and the ascendance of biology as the dominant science of the 21st century. Sequencing revealed that >90% of the human genome is not coding for proteins, as originally thought, but rather is overwhelmingly transcribed into non‐protein coding, or non‐coding, RNAs (ncRNAs). This discovery initially led to the hypothesis that most genomic DNA is “junk”, a term still championed by some geneticists and evolutionary biologists. In (...) contrast, molecular biologists and biochemists studying the vast number of transcripts produced from most of this genome “junk” often surmise that these ncRNAs have biological significance. What gives? This essay contrasts the two opposing, extant viewpoints, aiming to explain their bases, which arise from distinct reference frames of the underlying scientific disciplines. Finally, it aims to reconcile these divergent mindsets in hopes of stimulating synergy between scientific fields. (shrink)

Since the ENCODE project published its final results in a series of articles in 2012, there is no consensus on what its implications are. ENCODE’s central and most controversial claim was that there is essentially no junk DNA: most sections of the human genome believed to be «junk» are functional. This claim was met with many reservations. If researchers disagree about whether there is junk DNA, they have first to agree on a concept of function and how (...) function, given a particular definition, can be discovered. The ENCODE debate centered on a notion of function that assumes a strong dichotomy between evolutionary and non-evolutionary function and causes, prevalent in the Modern Evolutionary Synthesis. In contrast to how the debate is typically portrayed, both sides share a commitment to this distinction. This distinction is, however, much debated in alternative approaches to evolutionary theory, such as the EES. We show that because the ENCODE debate is grounded in a particular notion of function, it is unclear how it connects to broader debates about what is the correct evolutionary frame- work. Furthermore, we show how arguments brought forward in the controversy, particularly arguments from mathematical population genetics, are deeply embedded in their particular disciplinary contexts, and reflect substantive assumptions about the evolution of genomes. With this article, we aim to provide an anatomy of the ENCODE debate that offers a new perspective on the notions of function both sides employed, as well as to situate the ENCODE debate within wider debates regarding the forces operating in evolution. (shrink)

Transposable elements are no longer considered to be “junk” DNA. Here, we review how TEs can impact gene regulation systematically. TEs encode various regulatory elements that enables them to regulate gene expression. RJ Britten and EH Davidson hypothesized that TEs can integrate the function of various transcriptional regulators into gene regulatory networks. Uniquely TEs can deposit regulatory sites across the genome when they transpose, and thereby bring multiple genes under control of the same regulatory logic. Several studies together have (...) robustly established that TEs participate in embryonic development and oncogenesis. We discuss the regulatory characteristics of TEs in context of evolution to understand the extent of their impact on gene networks. Understanding these features of TEs is central to future investigations of TEs in cellular processes and phenotypic presentations, which are applicable to development and disease studies. We re-visit the Britten–Davidson “gene-battery” model and understand the genetic and transcriptional impact of TEs in innovating gene regulatory networks. Transposable elements are exogenous sequences that have either been co-opted or repurposed for host functions. The vast amounts of TE sequence in the genome provides raw material for gene expression regulation, and still remains to be fully understood; the “gene-battery” model provides the basis for understanding this. (shrink)

The concept of inreducible complexity is central to the origins controversy. Ineducible complexity (IC) may be defined as any machine or system that requires two or more parts in order to function. Examples range from molecules to mousetraps, organelles, and organisms such as humans. This essay explores the relationship between IC and complexity, clarifying the levels of IC such as the irreducible core and its mode of function. IC has been used in a wide variety of disciplines for over a (...) century. Objections to irreducibte complexity include co-option, the "junk DNA" theory, and the scaffolding argument. Co-option, a major argument against IC, attempts to explain how IC can be achieved through natural means by utilizing existing parts to construct a new biological machine or structure. Yet examples of IC in both the biological and non-biological wortds show that such common objections do not invalidate the concept. IC is firmly established. (shrink)

This paper applies the conceptual toolkit of Evolutionary Developmental Biology (evo‐devo) to the evolution of the genome and the role of the genome in organism development. This challenges both the Modern Evolutionary Synthesis, the dominant view in evolutionary theory for much of the 20th century, and the typically unreflective analysis of heredity by evo‐devo. First, the history of the marginalization of applying system‐thinking to the genome is described. Next, the suggested framework is presented. Finally, its application to the evolution of (...) genome modularity, the evolution of induced mutations, the junk DNA versus ENCODE debate, the role of drift in genome evolution, and the relationship between genome dynamics and symbiosis with microorganisms are briefly discussed. (shrink)

Within the last decade, thousands of studies have described communication processes in and between organisms. Pragmatic philosophy of biology views communication processes as rule-governed sign-mediated interactions (rsi's). As sign-using individuals exhibit a relationship to following or not-following these rules, the rsi's of living individuals dier fundamentally from cause-and-effect reactions with and between non-living matter, which exclusively underlie natural laws. Umwelt thus becomes a term in investigating physiological influences on organisms that are not components of rsi's. Mitwelt is a term for (...) the investigation of all rsi's of organisms. Living organisms are never solus ipse subjects of semioses, but share common sets of rules and signs. Life depends decisively on symbiotic communities. Serial Endosymbiotic Theory proved that the evolution of the eukaryotic super-kingdom was a merger of anchestral bacteria. The integration of bacterial genomes into eukaryotic genomes was also a step from analog to symbolic genetic codes. Now we know, that so-called ‘junk DNA’ has higher order regulatory functions on genome architecture and protein coding DNA plays only the role of a structural vocabulary. (shrink)

The caliber of recent discourse regarding geneticallymodified organisms (GMOs) has suffered from a lack of consensuson terminology, from the scarcity of evidence upon which toassess risk to health and to the environment, and from valuedifferences between proponents and opponents of GMOs. Towardsaddressing these issues, we present the thesis that GM should bedefined as the forcible insertion of DNA into a host genome,irrespective of the source of the DNA, and exclusive ofconventional or mutation breeding.Some defenders of the commercial use of GMOs (...) have referred to thescientific work of GMO critics as ``junk science.'''' Such a claim isfalse and misleading, given that many papers critical of both theutility and safety of GMOs have been published in peer reviewedjournals by respected scientists. In contrast, there is a dearthof peer reviewed work to substantiate the frequently heardassertions of either safety or utility in GMOs. The polarity,which now characterizes much of the public discourse on GMOs,reflects not simply scientific disagreement, but alsodisagreement in underlying value assumptions. Value differencesstrongly affect the assessment of both benefit and harm fromGMOs. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:The Human Genome ProjectSharon J. Durfy (bio) and Amy E. Grotevant (bio)In recent years, scientists throughout the world have embarked upon a long-term biological investigation that promises to revolutionize the decisions people make about their lives and lifestyles, the way doctors practice medicine, how scientists study biology, and the way we think of ourselves as individuals and as a species. It is called the Human Genome Project, and its (...) ultimate goal is to map and determine the chemical sequence of the three billion nucleotide base pairs that comprise the human genome. The feat is expected to take about fifteen years (see General Surveys).These three billion base pairs include an estimated 50,000 to 100,000 genes. The rest of the genome—perhaps 95 percent of it—is nongenic sequences with unknown function, sometimes called "junk." Determining the order and organization of all this material has been likened to tearing six volumes of the Encyclopaedia Brittanica into pieces, then trying to put it all back together to read the information (Surveys: Hall 1990). The effort could be well worth it, many scientists say, because it is expected to yield major insights into many common and complex diseases, including cancer, cardiovascular disease, and Alzheimer's disease (Debate: Dulbecco 1986; Koshland 1989).The Human Genome Project is not without controversy, however (Debate: Davis 1990; Leder 1990; Rechsteiner 1990). Many scientists fear that funding for it will be diverted from other areas of research, rather than obtained from new funding sources. This has enlivened the debate about the relative value of "big" versus "small" science. Also, the value of undertaking a complete sequencing of the genome has been questioned, especially given the high proportion of non-genic sequences.Advocates of the effort converted many critics by making two alterations in the original plan. Plans were included to simultaneously determine the nucleotide sequence of the genomes of other organisms; this provides comparisons and points of reference for the human sequence (U.S.: NIH/DOE 1990). Second, in response to concerns about the high cost of developing technology to sequence the whole [End Page 347] genome, the focus moved from large-scale sequencing to mapping the genome, which would hasten the search for disease genes (U.S.: NIH/DOE 1990).The ideal map would be both genetic, locating DNA markers, or signposts, at closely spaced intervals along the chromosomes, and physical, indicating the exact distance between these markers (Map: McKusick 1991). Since 1973, Human Gene Mapping workshops (HGM) have been held at least every two years to locate, compare, and compile genetic markers. This information is published and is accessible through Genome Database at Johns Hopkins University (McKusick 1991). The most recent Human Genome Mapping workshop was held in August 1991, at which the Human Genome Organization (HUGO) began to assume increased responsibility for coordination of the international mapping effort (Surveys: Maddox 1991).Historical Background of the United States EffortThe first serious discussions about sequencing the entire human genome occurred at a workshop at the University of California at Santa Cruz in 1985 (U.S.: Sinsheimer 1989). A second workshop, organized by the U.S. Department of Energy (DOE) and held in March 1986, addressed the feasibility of an organized program (U.S.: DOE 1986). Shortly thereafter, DOE instituted its own genome project (U.S.: DOE 1987). Reports in early 1988 from both the National Research Council (NRC) of the National Academy of Sciences (NAS) and Congress' Office of Technology Assessment (OTA) (U.S.: NRC 1988; OTA 1988) served as catalysts, and in fiscal year 1988, the U.S. Congress officially launched the Human Genome Project by appropriating funds to both the Department of Energy and the National Institutes of Health (NIH).To avoid potential congressional "meddling" (U.S.: Roberts 1988), NIH and DOE drafted a memorandum of understanding for interagency coordination in October 1988 (U.S.: NIH/DOE 1990). The agencies then created both separate and joint committees, and working groups to administer the project. NIH established the Office of Human Genome Research in 1988 (directed by James D. Watson) to plan and coordinate NIH genome activities. That office has evolved into the National Center for Human Genome Research (NCHGR... (shrink)

Scientific evidence is often more reliable than other types of evidence commonly used in criminal trials – i.e., eyewitness identifications, confessions, and informant testimony. Nevertheless, despite its obvious value, forensic science has not always merited the term “science.” Three developments in the 1990s focused attention on its shortcomings: the advent of DNA profiling, the Supreme Court's “junk science” decision, and a number of wellpublicized crime laboratory scandals. In light of these developments, and in order to take full advantage of (...) the power of forensic science to aid in the search for truth, a number of reforms are needed: Crime laboratories should be accredited, lab procedures should be standardized, and basic research needs to be conducted on many commonly used techniques. Court procedures also require improvement: Defense experts should be more readily available to indigent defendants, and more comprehensive pretrial disclosure of the substance of expert testimony should be provided. (shrink)

Despite being a major theorist of post-war Marxism in the German-speaking world, Leo Kofler remains largely unknown outside of it. This volume introduces his work and life and presents six of Kofler’s essays in English for the first time.

Ziel des PVS Sonderheftes ist es, die seit einiger Zeit boomende Konjunktur des Verantwortungsbegriffs zu reflektieren, die Relevanz dieses Begriffes zu analysieren und seinen Wandel angesichts gesellschaftlicher und technischer Veranderungen zu erfassen. Eines der wichtigsten Kriterien zur Beurteilung politischer Entscheidungen ist deren Verantwortlichkeit. Der Begriff der Verantwortung bezieht sich auf einen Rahmen normativer Erwartungen, die je nach Politikfeld starker rechtlich oder moralisch ausgepragt sind. Verantwortung bedeutet insbesondere, einem Akteur die Folgen seines Handels zuschreiben zu konnen. Ein Kernproblem aktueller Verantwortungskonzeptionen besteht (...) in der Diffusion von Verantwortung. Einerseits sind immer mehr Akteure an immer mehr Handlungszusammenhangen beteiligt, aber gleichzeitig sind immer weniger Akteure fur ihre Handlungsfolgen allein verantwortlich. Die Beitrage des Heftes diskutieren die Folgen dieser Dilemmata sowohl in ihren theoretischen Konsequenzen als auch empirisch anhand verschiedener Felder lokaler, nationaler und internationaler Politik. Der Band versammelt Expertinnen und Experten aus unterschiedlichen Disziplinen: von der Politikwissenschaft uber die Rechtswissenschaft bis hin zur Soziologie und Philosophie. (shrink)

DNA supercoiling is one of the mechanisms that can help unlinking of newly replicated DNA molecules. Although DNA topoisomerases, which catalyze the strand passing of DNA segments through one another, make the unlinking problem solvable in principle, it remains difficult to complete the process that enables the separation of the sister duplexes. A few different mechanisms were developed by nature to solve the problem. Some of the mechanisms are very intuitive while the others, like topology simplification by type II DNA (...) topoisomerases and DNA supercoiling, are not so evident. A computer simulation and analysis of linked sister plasmids formed inEscherichia colicells with suppressed topoisomerase IV suggests an insight into the latter mechanism. (shrink)

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)

Epistemic consequentialism has been challenged on the grounds that it is overly demanding. According to the Epistemic Junk Problem, this view implies that we are often required to believe junk propositions such as ‘the Great Bear Lake is the largest lake entirely in Canada’ and long disjunctions of things we already believe. According to the Numerosity Problem, this view implies that we are frequently required to have an enormous number of beliefs. This paper puts forward a novel version (...) of epistemic consequentialism which avoids these twin demandingness problems. The key is to recognise, first, that the final epistemic value of a true belief depends at least in part on the duration for which it is retained by the agent and, second, that our cognitive makeup places important constraints on which beliefs are retained and for how long. (shrink)

The recent exchange between Glenn Yago and James W. Brock over the junk?bond buyouts of the 1980s missed the mark on a number of points. In reality, neither the buyouts nor their sudden near?cessation contributed materially to the recession of 1990?91. The buyout wave did not end primarily because of new restrictive regulations. The buyouts had no appreciable effect on real capital formation. And the increased rate of bankruptcies resulting from the buyouts left the economy's overall efficiency unimpaired.

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)

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)

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)

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)

Science; Ethics; Politics; Beyond recombinant dna.

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)

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)

All parts of mereologically ‘gunky’ entities have proper parts. All parts relevant to mereologically ‘junky’ entities *are* proper parts. This essay explores the application of gunk and junk beyond the standard category of material object. One such application yields what is here dubbed ‘deep’ gunk and junk: a material entity x all of whose intrinsic elements from any fundamental ontological category C either have proper parts from C that also are intrinsic elements of x, or are proper parts (...) of entities from C that also are intrinsic elements of x. In addition to being independently interesting, these mereological structures pose a challenge to the bare particular ontology of substance. For bare particulars standardly are assumed to be mereologically simple, yet a deep gunky or junky entity requires any associated bare particulars to be complex. The essay closes by examining the bare particular theorist’s prospects for answering this challenge. (shrink)

In this paper I revisit Gilbert Harman's arguments for a "clutter avoidance" norm. The norm -- which says that we ought to avoid cluttering our minds with trivialities -- is widely endorsed. I argue that it has some fairly dramatic consequences for normative epistemology.

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)

For nearly two decades, nonengineered human DNA was patented without challenge. The US Supreme Court recently agreed that many of those patents do not fit accurately into any currently accepted scheme of intellectual property protection. One should consider: whether DNA fits into other forms of property protection (land, moveables, chattels, etc.); whether DNA warrants a new and unique form of property protection, or whether DNA belongs to the class of objects generally considered to be as “the commons.” Current schemes of (...) patent protection for genes are entirely new, unwarranted by precedent, and utterly aberrant in applying the law of patent. Nonetheless, it bears examining how intellectual property schemes might serve as guidance for new forms of intellectual property protection for genes, if indeed those genes fit into classical dimensions of intellectual property. Private ownership of property has emerged as the dominant legal institution covering modes of possession. (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.

Abstract6‐methyladenine (6mA) is fairly abundant in nuclear DNA of basal fungi, ciliates and green algae. In these organisms, 6mA is maintained near transcription start sites in ApT context by a parental‐strand instruction dependent maintenance methyltransferase and is positively associated with transcription. In animals and plants, 6mA levels are high only in organellar DNA. The 6mA levels in nuclear DNA are very low. They are attributable to nucleotide salvage and the activity of otherwise mitochondrial METTL4, and may be considered as a (...) price that cells pay for adenine methylation in RNA and/or organellar DNA. Cells minimize this price by sanitizing dNTP pools to limit 6mA incorporation, and by converting 6mA that has been incorporated into DNA back to adenine. Hence, 6mA in nuclear DNA should be described as an epigenetic mark only in basal fungi, ciliates and green algae, but not in animals and plants. (shrink)

Many philosophers and psychologists who approach the issue of representation from a computational or measurement theoretical perspective end up having to deny the possibility of junk representations—representations present in an organism's head but that enter into no psychological processes or produce no behaviour. However, I argue, a more functional perspective makes the possibility of junk representations intuitively quite plausible—so much so that we may wish to question those views of representation that preclude the possibility of junk representations. (...) I explore some of the reasons we should care about the possibility of junk representations and conclude with some speculation about whether junk representations are in fact present in our heads. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Noël Carroll THE PARADOX OFJUNK FICTION Perhaps on your way to some academic conference, if you had no papers to grade, you stopped in die airport gift shop for something to read on the plane. You saw racks of novels authored by die likes of Mary Higgins Clark, Michael Crichton, John Grisham, Danielle Steele, Sidney Sheldon, Stephen King, Sue Grafton, Elmore Leonard, Sara Paretsky, Tom Clancy, and so on. (...) These are the kinds of novels that, when you lend them to friends, you don't care, unless you live in Bowling Green, Ohio, whether you ever get them back. They are mass, popular fictions. In another era, they would have been called pulp fictions. Following Thomas Roberts,1 I will call diem junk fictions, under which rubric I will also include things like Harlequin romances; sci-fi, horror, and mystery magazines; comic books; and broadcast narratives on either the radio or TV, as well as commercial movies. There are a number of interesting philosophical questions diat we may ask aboutjunk fiction. We could, for example, attempt to characterize its essential features. However, for the present, I will assume that the preceding examples are enough to provide you with a rough-andready notion of what I am calling junk fiction, and I will attempt to explore anotiier feature of the phenomenon, viz., what I call the paradox ofjunk fiction. Thejunk fictions that I have in mind are all narratives. Indeed, dieir story dimension is die most important thing about diem. Stephen King, for instance, makes diis point by saying that he is primarily a story teller rather than a writer. Junk fictions aspire to be page-turners—the blurb on the cover of Stillwatch by Mary Higgins Clark says that it is "designed to be read at breatiitaking speed"—and what motivates turning die page so quickly is our interest in what happens next. We do not dawdle Philosophy and Literature, © 1994, 18: 225-241 226Philosophy and Literature over Clark's diction as we might over Updike's nor do we savor die complexity of her sentence structure, as we do widi Virginia Woolfs. Radier, we read for story. Moreover, junk fictions are die sort of narratives that commentators are wont to call formulaic. That is, junk fictions generally belong to well-entrenched genres, which diemselves are typified by tiieir possession of an extremely limited repertoire of story-types. For example, as John Cawelti has pointed out, one such recurring Western narrative is diat of the recendy pacifist gunfighter, like Shane, who is forced by circumstances to take up his pistols again, widi altogedier devastating effect.2 Junk fictions tell diese generic stories again and again with minor variations. Sometimes diese variations may be quite clever and unexpected. Agatiia Christie was the master of this; she was able to use the conventions of the mystery genre in order to "hide" her murderers. In TheMurderofRogerAckroyd, she "secrets" the murderer in the personage of the narrator; in Ten Little Indians, die murderer is a "dead man"; while in Murder on the Orient Express, all the suspects did it. In each of these cases, Christie's brilliance hinges upon her playing (and preying) upon conventional expectations. Neverdieless, even diese surprising variations require a well-established background of narrative forms. That is, in order to appreciate diese variations, die reader must in some sense know die standard story already. And with junk fiction, it is generally fair to say that in some sense, the reader—or, at least, the reader who has read around in die genre before—knows in rough oudine how die story is likely to go. Readers and/or viewers of Jurassic Park surmised, once die dinosaur enclosures were described, diat in fairly short order die dinosaurs would trample them down and go on the rampage—after all we had already seen or read The Lost World, King Kong, and their progeny. So, junk fictions are formulaic. They rehearse certain narrative formats again and again. And, furthermore, in some very general sense, the audience already knows die story in question. But this knowledge on die part of die audience provokes a question, specifically, why if the reader, viewer or listener already... (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)

The sciences of genetics and genomics are revealing more all the time regarding our statuses as individuals relative to our particular genomes. Geographical isolation is presumably the greatest factor in allowing for populations of a species to change genetically over time, in response to environmental pressures and genetic drift accelerated by the mechanism of sexual reproduction. In order to develop a robust account of what rights individual members of the human species might have to either their own particular DNA or (...) the human genome in general, one need to explain the relations between individuals and species in regards to deoxyribonucleic acid (DNA). The fact that genes carry over from species to species does not mean that those genes are completely identical across all species. Laws and regulations exist that govern the use of human tissues and property rights over their products. (shrink)

DNA profiling is a well-established technology for use in the criminal justice system, both in courtrooms and elsewhere. The fact that DNA profiles are based on non-coding DNA and do not reveal details about the physical appearance of an individual has contributed to the acceptability of this type of evidence. Its success in criminal investigation, combined with major innovations in the field of genetics, have contributed to a change of role for this type of evidence. Nowadays DNA evidence is not (...) merely about identification, where trace evidence is compared to a sample taken from a suspect. An ever-growing role is anticipated for DNA profiling as an investigative tool, a technique aimed at generating a suspect where there is none. One of these applications is the inference of visible traits. As this article will show, racial classifications are at the heart of this application. The Netherlands and its legal regulation of 'externally visible traits' will serve as an example. It will be shown that, to make this technology work, a large number of actors has to be enrolled and their articulations invited. This indicates that instead of a 'silent witness', a DNA profile should rather be seen as an 'articulate collective'. Based on two cases, I argue that the normativity of visible traits is context-dependent. Taking into account the practices in which technology is put to use alerts us to novel ethical questions raised by their application. (shrink)

Here, the emerging data on DNA G‐quadruplexes (G4s) as epigenetic modulators are reviewed and integrated. This concept has appeared and evolved substantially in recent years. First, persistent G4s (e.g., those stabilized by exogenous ligands) were linked to the loss of the histone code. More recently, transient G4s (i.e., those formed upon replication or transcription and unfolded rapidly by helicases) were implicated in CpG island methylation maintenance and de novo CpG methylation control. The most recent data indicate that there are direct (...) interactions between G4s and chromatin remodeling factors. Finally, multiple findings support the indirect participation of G4s in chromatin reshaping via interactions with remodeling‐related transcription factors (TFs) or damage responders. Here, the links between the above processes are analyzed; also, how further elucidation of these processes may stimulate the progress of epigenetic therapy is discussed, and the remaining open questions are highlighted. (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)

Definition of the problem:The frequency and scope of human genetic banking has increased significantly in recent years and is set to expand still further. Two of the major growth areas in medical research, pharmacogenomics and population genetics, rely on large DNA banks to provide extensive, centralised and standardised genetic information as well as clinical and personal data. This development raises ethical concerns. Arguments and conclusion: Our article focuses on the appropriateness of informed consent as a means to safeguard both research (...) subjects’ rights and their good will. It will be argued that information requirements are extensive, with regard to non-therapeutic research, feedback, type of consent and possible breaches of confidentiality as well as possible implications for third parties. Given the demand of these requirements and the danger that research facilitated by these huge DNA banks may not reflect public priorities, it is argued that the research needs be steered by trustees to ensure that the altruistic act of sample donation contributes to the public good. (shrink)

Under the terms of the UN Convention on the Rights of the Child, which Australia has ratified, children have a right to know who their genetic parents are. As a result, we have a duty to establish these facts and to make this information available for children to access should they wish to know. Introducing mandatory DNA testing of newborns and their alleged genetic parents is one viable option to ensure that this information is available for children to access. Indeed, (...) it may be the only viable option to address childrens' right to the fulfilment of Article 7 of the CRC. There are a number of benefits to obtaining this benefit for children. For one, mandatory DNA testing could solve all disputed paternity cases and finalise them early in the lives of children, thus making life more financially secure for those children in the long term. This could reduce or eliminate the need for fathers to secretly carry out DNA tests in order to disestablish paternity. The large number of benefits gained from identifying genetic parents for children and the small possible risks that they may suffer when this information is withheld give us good reasons to support mandatory DNA testing. (shrink)