The logic of genetic discovery has changed little over time, but the focus of biology is shifting from simple genotype–phenotype relationships to complex metabolic, physiological, developmental, and behavioral traits. In light of this, the traditional reductionist view of individual genes as privileged difference‐making causes of phenotypes is re‐examined. The scope and nature of genetic effects in complex regulatory systems, in which dynamics are driven by regulatory feedback and hierarchical interactions across levels of organization are considered. This review (...) argues that it is appropriate to treat genes as specific actual difference‐makers for the molecular regulation of gene expression. However, they are often neither stable, proportional, nor specific as causes of the overall dynamic behavior of regulatory networks. Dynamical models, properly formulated and validated, provide the tools to probe cause‐and‐effect relationships in complex biological systems, allowing to go beyond the limitations of genetic reductionism to gain an integrative understanding of the causal processes underlying complex phenotypes. (shrink)

Networks for the exchange and/or sharing of genetic data are developing in many countries. We focus here on the situations in the US and France. We highlight some recent and remarkable differences between these two countries concerning the mode of access to, and the storage and use of genetic data, particularly as concerns two-sided markets and dynamic consent or dynamic electronic informed consent. This brief overview suggests that, even though the organization and function of these two-sided markets remain (...) open to criticism, dynamic e-IC should be more widely used, especially in France, if only to determine its real effectiveness. (shrink)

People respond to metaphors as much with regard to the emotions that they generate as to their referential, comparative contents. Interviews with non-geneticists about preferred metaphors for gene-environment interaction that illustrate this tendency are reported. These interviews also reveal the dynamic tendency of such emotional responses. A second set of interviews shows that lay people may preferentially use a metaphor of "virus" or "disease" for talking about genes, as opposed to the coding metaphors transmitted through the mass media and reportedly (...) preferred by geneticists. An explanation based on the differently situated emotions of these groups is proposed. It is proposed that the prominence of emotions in responding to genetics indicates the importance of incorporating analyses of emotions instead of simple principles into policy formulation about genetics. (shrink)

A substantial portion of the human genome has been found to consist of simple sequence repeats, including microsatellites and minisatellites. Microsatellites, tandem repeats of 1–6 nucleotides, form the template for dynamic mutations, which involve heritable changes in the lengths of repeat sequences. In recent years, a large number of human disorders have been found to be caused by dynamic mutations, the most common of which are trinucleotide repeat expansion diseases. Dynamic mutations are common to numerous nervous system disorders, including Huntington's (...) disease, various spinocerebellar ataxias, fragile X syndrome, fragile X tremor/ataxia syndrome, Friedreich ataxia and other neurodegenerative disorders. The involvement of dynamic mutations in brain disorders will be reviewed, with a focus on the large group caused by CAG/glutamine repeat expansions. We will also outline a proposed role of tandem repeat polymorphisms (TRPs), with unique ‘digital’ genetic distributions, in modulating brain development and normal function, so as to generate additional mutational diversity upon which natural selection may act. BioEssays 29:525–535, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

How do common and rare genetic polymorphisms contribute to quantitative traits or disease risk and progression? Multiple human traits have been extensively characterized at the genomic level, revealing their complex genetic architecture. However, it is difficult to resolve the mechanisms by which specific variants contribute to a phenotype. Recently, analyses of variant effects on molecular traits have uncovered intermediate mechanisms that link sequence variation to phenotypic changes. Yet, these methods only capture a fraction of genetic contributions to (...) phenotype. Here, in reviewing the field, it is proposed that complex traits can be understood by characterizing the dynamics of biochemical networks within living cells, and that the effects of genetic variation can be captured on these networks by using protein–protein interaction (PPI) methodologies. This synergy between PPI methodologies and the genetics of complex traits opens new avenues to investigate the molecular etiology of human diseases and to facilitate their prevention or treatment. (shrink)

As emphasized in early cultural evolutionary theory, understanding heritability of human traits – especially, behavioural traits – is difficult. The target article describes important ways that culture can enhance, or obscure, signatures of heritability in genetic studies. Here, we discuss the utility of calculating heritability for behavioural traits influenced by cultural evolution and point to conceptual and technical complications to consider in future models.

The advent of CRISPR has drastically moved the possibility of genetically modifying human genomes from the space of science fiction into nearby reality. Whether one considers the positive results f...

Dynamic Consent is both a model and a specific web-based tool that enables clear, granular communication and recording of participant consent choices over time. The DC model enables individuals to know and to decide how personal research information is being used and provides a way in which to exercise legal rights provided in privacy and data protection law. The DC tool is flexible and responsive, enabling legal and ethical requirements in research data sharing to be met and for online health (...) information to be maintained. DC has been used in rare diseases and genomics, to enable people to control and express their preferences regarding their own data. However, DC has never been explored in relationship to historical collections of bioscientific and genetic heritage or to contexts involving Aboriginal and Torres Strait Islander people.In response to the growing interest by First Peoples throughout Australia in genetic and genomic research, and the increasing number of invitations from researchers to participate in community health and wellbeing projects, this article examines the legal and ethical attributes and challenges of DC in these contexts. It also explores opportunities for including First Peoples' cultural perspectives, governance, and leadership as a method for defining DC on cultural terms that engage best practice research and data analysis as well as respect for meaningful and longitudinal individual and family participation. (shrink)

Participatory Technology Assessment initiatives have usually been analyzed as if they existed in a social and political vacuum. This article analyzes the linkages that occur, in both directions, between the microcosm set up by a pTA exercise and the real world outside. This dual-dynamics perspective leads to a new way of understanding the function and significance of pTA initiatives. Rather than viewing them as a means to create the ideal conditions for real public debate, they are viewed here as (...) an additional public arena in which sociotechnical controversies are played out. This perspective is developed from the analysis of an interactive technology assessment exercise conducted by the French National Institute for Agricultural Research, on the topic of genetically modified vines. (shrink)

Communicating genetic information to family members has been the subject of an extensive debate recently in bioethics and law. In this context, the extent of the relatives’ right to know and not to know is examined. The mainstream in the bioethical literature adopts a liberal perception of patient autonomy and offers a utilitarian mechanism for solving familial tensions over genetic information. This reflects a patient-centred approach in which disclosure without consent is justified only to prevent serious harm or (...) death to others. Based on a legal and bioethical analysis on the one hand, and an examination of empirical studies on the other, this paper advocates the adoption of a relational perception of autonomy, which, in the context of genetics, takes into account the effect that any decision—whether to disclose or not to disclose—will have on the familial relationship and the dynamics of the particular family. Adding this factor to the criteria usually advocated by lawyers and ethicists will facilitate reaching a sensitive decision, which recognises the various interests of family members beyond the risk to physical health. Taking this factor into account will require a process of deliberation both between doctors and patients, and in the family. It will also require a relaxation of medical confidentiality, as the family rather than the patient is gradually perceived as the unit of care. Moreover, adopting such a relational approach will accord with current views of doctors and patients who base their decision primarily on the nature of the familial relationship. (shrink)

Beyond belief change and meme adoption, both genetics and infection have been spoken of in terms of information transfer. What we examine here, concentrating on the specific case of transfer between sub-networks, are the differences in network dynamics in these cases: the different network dynamics of germs, genes, and memes. Germs and memes, it turns out, exhibit a very different dynamics across networks. For infection, measured in terms of time to total infection, it is network type rather (...) than degree of linkage between sub-networks that is of primary importance. For belief transfer, measured in terms of time to consensus, it is degree of linkage rather than network type that is crucial. Genes model each of these other dynamics in part, but match neither in full. For genetics, like belief transfer and unlike infection, network type makes little difference. Like infection and unlike belief, on the other hand, the dynamics of genetic information transfer within single and between linked networks are much the same. In ways both surprising and intriguing, transfer of genetic information seems to be robust across network differences crucial for the other two. (shrink)

This paper presents the architecture and initial feasibility results of a proto-type communication network that utilizes genetic programming to evolve services and protocols as part of network operation. The network evolves responses to environmental conditions in a manner that could not be preprogrammed within legacy network nodes a priori. A priori in this case means before network operation has begun. Genetic material is exchanged, loaded, and run dynamically within an active network. The transfer and execution of code in (...) support of the evolution of network protocols and services would not be possible without the active network environment. Rapid generation of network service code occurs via a genetic programming paradigm. Complexity and Algorithmic Information Theory play a key role in understanding and guiding code evolution within the network. (shrink)

The study of mental illness by the methods of molecular genetics is still in its infancy, but the use of genetic markers in psychiatry may potentially lead to a Virchowian revolution in the conception of mental illness. Genetic markers may define novel clusters of patients having diverse clinical presentations but sharing a common genetic and mechanistic basis. Such clusters may differ radically from the conventional classification schemes of psychiatric illness. However, the reduction of even relatively simple Mendelian (...) phenomena to molecular genetics has been shown to be a surprisingly complex and problematic enterprise. Mental illnesses exist at many levels of including social, environmental, and developmental interactions. Reductionistic shifts in the classification of such a disease entity will have to address the interlevel dynamics that take place within the structure of theories of mental illness. The question of how molecular analysis of psychiatric disease will impact on the structure of existing theories and classification systems is the central topic of this paper. (shrink)

Behavioral genetics and cultural evolution have both revolutionized our understanding of human behavior – largely independent of each other. Here, we reconcile these two fields under a dual inheritance framework, offering a more nuanced understanding of the interaction between genes and culture. Going beyond typical analyses of gene–environment interactions, we describe the cultural dynamics that shape these interactions by shaping the environment and population structure. A cultural evolutionary approach can explain, for example, how factors such as rates of innovation (...) and diffusion, density of cultural subgroups, and tolerance for behavioral diversity impact heritability estimates, thus yielding predictions for different social contexts. Moreover, when cumulative culture functionally overlaps with genes, genetic effects become masked, unmasked, or even reversed, and the causal effects of an identified gene become confounded with features of the cultural environment. The manner of confounding is specific to a particular society at a particular time, but a WEIRD (western, educated, industrialized, rich, and democratic) sampling problem obscures this boundedness. Cultural evolutionary dynamics are typically missing from models of gene-to-phenotype causality, hindering generalizability of genetic effects across societies and across time. We lay out a reconciled framework and use it to predict the ways in which heritability should differ between societies, between socioeconomic levels, and other groupings within some societies but not others, and over the life course. An integrated cultural evolutionary behavioral genetic approach cuts through the nature–nurture debate and helps resolve controversies in topics such as IQ. (shrink)

Behaviors are quantitative traits determined through actions of multiple genes and subject to genome–environment interactions. Early studies concentrated on analyzing the effects of single genes on behaviors, often generating views of simplified linear genetic pathways. The genome era has generated a profound paradigm shift enabling us to identify all the genes that contribute to expression of a behavioral phenotype, to investigate how they are organized as functional ensembles and to begin to identify polymorphisms that contribute to phenotypic variation and (...) are targets for natural selection. Recent studies show that the genetic architecture of behavior is determined by dynamic and plastic modular networks of pleiotropic genes and that the behavioral phenotype manifests itself as an emergent property of such networks. Such networks are exquisitely sensitive to genetic background and sex effects. This review describes how Drosophila can serve as a model for uncovering fundamental principles of the genetic architecture of behavior. BioEssays 26:1299–1306, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Recent advances in genomic and imaging techniques have revealed the complex manner of organizing billions of base pairs of DNA necessary for maintaining their functionality and ensuring the proper expression of genetic information. The SMC proteins and cohesin complex primarily contribute to forming higher‐order chromatin structures, such as chromosomal territories, compartments, topologically associating domains (TADs) and chromatin loops anchored by CCCTC‐binding factor (CTCF) protein or other genome organizers. Cohesin plays a fundamental role in chromatin organization, gene expression and regulation. (...) This review aims to describe the current understanding of the dynamic nature of the cohesin‐DNA complex and its dependence on cohesin for genome maintenance. We discuss the current 3C technique and numerous bioinformatics pipelines used to comprehend structural genomics and epigenetics focusing on the analysis of Cohesin‐centred interactions. We also incorporate our present comprehension of Loop Extrusion (LE) and insights from stochastic modelling. (shrink)

The chapter explains why evolutionary genetics – a mathematical body of theory developed since the 1910s – eventually got to deal with culture: the frequency dynamics of genes like “the lactase gene” in populations cannot be correctly modeled without including social transmission. While the body of theory requires specific justifications, for example meticulous legitimations of describing culture in terms of traits, the body of theory is an immensely valuable scientific instrument, not only for its modeling power but also for (...) the amount of work that has been necessary to build, maintain, and expand it. A brief history of evolutionary genetics is told to demonstrate such patrimony, and to emphasize the importance and accumulation of statistical knowledge therein. The probabilistic nature of genotypes, phenogenotypes and population phenomena is also touched upon. Although evolutionary genetics is actually composed by distinct and partially independent traditions, the most important mathematical object of evolutionary genetics is the Mendelian space, and evolutionary genetics is mostly the daring study of trajectories of alleles in a population that explores that space. The ‘body’ is scientific wealth that can be invested in studying every situation that happens to turn out suitable to be modeled as a Mendelian population, or as a modified Mendelian population, or as a population of continuously varying individuals with an underlying Mendelian basis. Mathematical tinkering and justification are two halves of the mutual adjustment between the body of theory and the new domain of culture. Some works in current literature overstate justification, misrepresenting the relationship between body of theory and domain, and hindering interdisciplinary dialogue. (shrink)

The acquisition and evolution of speech production, discourse and communication can be negatively impacted by brain malformations. We describe, for the first time, a case of developmental dynamic dysphasia (DDD) in a right-handed adolescent boy (subject D) with cortical malformations involving language-eloquent regions (inferior frontal gyrus) in both the left and the right hemispheres. Language evaluation revealed a markedly reduced verbal output affecting phonemic and semantic fluency, phrase and sentence generation and verbal communication in everyday life. Auditory comprehension, repetition, naming, (...) reading and spelling were relatively preserved, but executive function was impaired. Multimodal neuroimaging showed a malformed cerebral cortex with atypical configuration and placement of white matter tracts bilaterally and abnormal callosal fibers. Dichotic listening showed right hemisphere dominance for language and functional magnetic resonance imaging (fMRI) additionally revealed dissociated hemispheric language representation with right frontal activation for phonology and bilateral dominance for semantic processing. Moreover, subject D also had congenital mirror movements (CMM), defined as involuntary movements of one side of the body that mirror intentional movements of the other side. Transcranial magnetic stimulation and fMRI during voluntary unimanual (left and right) hand movements showed bilateral motor cortex recruitment and tractography revealed a lack of decussation of bilateral corticospinal tracts. Genetic testing aimed to detect mutations that disrupt the development of commissural tracts correlating with CMM (e.g., Germline DCC mutations) was negative. Overall, our findings suggest that DDD in subject D resulted from the underdevelopment of the left inferior frontal gyrus with limited capacity for plastic reorganization by its homologous counterpart in the right hemisphere. Corpus callosum anomalies probably contributed to hinder interhemispheric connectivity necessary to compensate language and communication deficits after left frontal involvement. (shrink)

The emergence of the genetic counseling profession has allowed laypeople to understand and benefit from biological advances, and to make critical decisions about their application. The discipline of genetic counseling has been criticized from its very beginning, in particular because of its early association with the eugenics movement. This paper presents a critical and reflective overview of how genetic counseling is implicitly embedded in the history of eugenics but also counteracts past eugenic practices and ideas. After World (...) War II, attempts were made to distance genetic counseling from eugenics. The first definition of genetic counseling did not position this field as a medical encounter but "as a kind of genetic social work aimed primarily to provide people with an understanding of their family's genetics problems." This approach was a reaction to the genetic and social evolutionary ideas that informed eugenic theories during the first half of the 20th century. Professionals engaged in genetic counseling during the 1940s and1950s rejected eugenic practices, but there was still support for eugenics’ goals of improving heredity and eliminating disease. From the 1960s, genetic counseling underwent professionalization alongside feminization and a definition of core values. Among these values were nondirectiveness counseling and the autonomy of the counselee. The dark shadow of Nazi ideology and other eugenic practices, attempts to employ the historical responsibility of geneticists, and the dynamic medical, social, political, and educational changes of the 1960s and 1970s helped to frame approaches and delineate the goals and limits of the new profession of “genetic counseling.”. (shrink)

I begin with a discussion of the value of privacy and what we lose without it. I then turn to the difficulties of preserving privacy for genetic information and other medical records in the face of advanced information technology. I suggest three alternative public policy approaches to the problem of protecting individual privacy and also preserving databases for genetic research:(1) governmental guidelines and centralized databases, (2) corporate self-regulation, and (3) my hybrid approach. None of these are unproblematic; I (...) discuss strengths and drawbacks of each, emphasizing the importance of protecting the privacy of sensitive medical and genetic information as well as letting information technology flourish to aid patient care, public health and scientific research. (shrink)

No longer viewed by scientists as the cell’s fixed master molecule, DNA is a dynamic script that is ad-libbed at each stage of development. What our parents hand down to us is just the beginning. Genetic Explanations urges us to replace our faith in genetic determinism with scientific knowledge about genetic plasticity and epigenetic inheritance.

We show how a simple nonlinear dynamical system (the discrete quadratic iteration on the unit segment) can be the basis for modelling the embryogenesis process. Such an approach, even though being crude, can nevertheless prove to be useful when looking with the two main involved processes:i) on one hand the cell proliferation under successive divisions ii) on the other hand, the differentiation between cell lineages. We illustrate this new approach in the case of Caenorhabditis elegans by looking at the early (...) stages of embryogenesis, up to several hundreds of cells (lima bean larval stage). We show how the many results that have been obtained by several groups can be interpreted in terms of values for the parameters controlling the dynamical system. Furthermore, we can extend the model to the cases of genetic mutations. More precisely the teratogenetic and lethal effects are associated with abnormal variation of the control parameters with time. (shrink)

While prior models of the evolution of altruism have assumed that organisms reproduce asexually, this paper presents a model of the evolution of altruism for sexually reproducing organisms using Hardy–Weinberg dynamics. In this model, the presence of reciprocal altruists allows the population to evolve to a stable polymorphic population where the majority of organisms are altruistic. Further, adding stochasticity leads to even larger numbers of altruists, while adding stochasticity to an analogous asexual model leads to more selfish organisms. The (...) contrast between these outcomes demonstrates why it may be important to pay attention to the underlying genetics of a population. (shrink)

Since the 1970s, the origin of cancer is being explored from the point of view of the Somatic Mutation Theory (SMT), focusing on genetic mutations and clonal expansion of somatic cells. As cancer research expanded in several directions, the dominant focus on cells remained steady, but the classes of genes and the kinds of extra-genetic factors that were shown to have causal relevance in the onset of cancer multiplied. The wild heterogeneity of cancer-related mutations and phenotypes, along with (...) the increasing complication of models, led to an oscillation between the hectic search of 'the' few key factors that cause cancer and the discouragement in face of a seeming 'endless complexity'. To tame this complexity, cancer research started to avail itself of the tools that were being developed by Systems Biology. At the same time, anti-reductionist voices began claiming that cancer research was stuck in a sterile research paradigm. This alternative discourse even gave birth to an alternative theory: the Tissue Organization Field Theory (TOFT). A deeper philosophical analysis shows the serious limits of both reductionist and anti-reductionist positions and of their polarization. This book demonstrates that a radical philosophical reflection is necessary to drive cancer research out of its impasses. At the very least, this will be a reflection on the assumptions of different kinds of cancer research, on the implications of what cancer research has been discovering over 40 years and more, on a view of scientific practice that is most able to make sense of the cognitive and social conflicts that are seen in the scientific community (and in its results), and, finally, on the nature of living entities with which we entertain this fascinating epistemological dance that we call scientific research. The proposed Dynamic and Relational View of carcinogenesis is a starting point in all these directions. (shrink)

This essay analyzes one of Germany's former premier research institutions for biomedical research, the Kaiser Wilhelm Institute for Anthropology, Human Heredity and Eugenics (KWIA) as a test case for the way in which politics and human heredity served as resources for each other during the Third Reich. Examining the KWIA from this perspective brings us a step closer to answering the questions at the heart of most recent scholarship concerning the biomedical community under the swastika: (1) How do we explain (...) why the vast majority of German human geneticists and eugenicists were willing to work for the National Socialist state and, at the very least, legitimized its exterminationist racial policy; and (2) what accounts for at least some of Germany's most renowned medically trained professionals' involvement in forms of morally compromised science that wholly transcend the bounds of normal scientific practice? Although a complete answer to this question must await an examination of other German biological research centers, the present study suggests that during the Nazi period the symbiotic relationship between human genetics and politics served to radicalize both. The dynamic between the science of human heredity and Nazi politics changed the research practice of some of the biomedical sciences housed at the KWIA. It also simultaneously made it easier for the Nazi state to carry out its barbaric racial program leading, finally, to the extermination of millions of so-called racial undesirables. (shrink)

How we age and what we can do about it have been uppermost in human thought since antiquity. The many false starts have frustrated experimentalists and theoretical arguments pronouncing the inevitability of the process have created a nihilistic climate among scientists and the public. The identification of single gene alterations that substantially extend life span in nematodes and flies however, have begun to reinvigorate the field. Drosophila's long history of contributions to aging research, rich storehouse of genetic information, and (...) powerful molecular techniques make it an excellent system for studying the molecular mechanisms underlying the process of aging. In recent years, Drosophila has been used to test current theories on aging and explore new directions of potential importance to the biology of aging. One such example is the surprising finding that, as opposed to the commonly held assumption that adult life is a period of random passive decline in which all things are thought to fall apart, the molecular life of the adult fly appears to be a state of dynamic well‐regulated change. In the fly, the level of expression of many different genes changes in an invariant, often age‐dependent, manner. These as well as other molecular genetic studies and demographic analyses using the fly have begun to challenge widely held ideas about aging providing evidence that aging may be a much more dynamic and malleable process than anticipated. With the enormous success that Drosophila molecular genetics has demonstrated in helping understand complex biological phenomena such as development there is much optimism that similar approaches can be adapted to assist in understanding the process of aging. BioEssays 25:134–141, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

M. xanthus has a complex multicellular lifestyle including swarming, predation and development. These behaviors depend on the ability of the cells to achieve directed motility across solid surfaces. M. xanthus cells have evolved two motility systems including Type‐IV pili that act as grappling hooks and a controversial engine involving mucus secretion and fixed focal adhesion sites. The necessity for cells to coordinate the motility systems and to respond rapidly to environmental cues is reflected by a complex genetic network involving (...) at least three complete sets of chemosensory systems and eukaryotic‐like signaling proteins. In this review, we discuss recent advances suggesting that motor synchronization results from spatial oscillations of motility proteins. We further propose that these dynamics are modulated by the action of multiple upstream complementary signaling systems. M. xanthus is thus an exciting emerging model system to study the intricate processes of directed cell migration. BioEssays 30:733–743, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

The dynamic developmental theory (DDT) has benefited from the insights of the commentators, particularly in terms of the implications for the proposed steepened delay gradients in attention-deficit/hyperactivity disorder (ADHD). The introduction of modified memory processes as a basis for the delay gradients improved the links to aspects of ADHD. However, it remains unclear whether the hyperactive-impulsive and inattentive subtypes are separate subgroups or may be explained as different outcomes of the same genetic factors and thus explicable by the same (...) principles. The DDT suggests that altered reinforcement and extinction processes define an endophenotype in ADHD that can be related dimensionally to inattention, hyperactivity, and impulsivity. The relation between the suggested endophenotype, characterized by changes in basic learning mechanisms, and other endophenotypes characterized by delay aversion or response disinhibition, needs to be tested in future studies. (shrink)

The dynamics of eukaryotic DNA polymerases has been difficult to establish because of the difficulty of tracking them along the chromosomes during DNA replication. Recent work has addressed this problem in the yeasts Schizosaccharomyces pombe and Saccharomyces cerevisiae through the engineering of replicative polymerases to render them prone to incorporating ribonucleotides at high rates. Their use as tracers of the passage of each polymerase has provided a picture of unprecedented resolution of the organization of replicons and replication origins in (...) the two yeasts and has uncovered important differences between them. Additional studies have found an overlapping distribution of DNA polymorphisms and the junctions of Okazaki fragments along mononucleosomal DNA. This sequence instability is caused by the premature release of polymerase δ and the retention of non proof‐read DNA tracts replicated by polymerase α. The possible implementation of these new experimental approaches in multicellular organisms opens the door to the analysis of replication dynamics under a broad range of genetic backgrounds and physiological or pathological conditions. (shrink)

Cover Photograph: Resolving developmental genetics in the fourth dimension: an illustration (by Kwang‐Hyun Cho himself) of the principle of dynamic network motifs in Drosophila development. Hitherto largely considered in terms of time‐invariant networks, drosophila development is viewed in the article by Man‐Sun Kim, Jeong‐Rae Kim, and Kwang‐Hyun Cho as the result of networks of gene interactions that change during the course of development. Using this paradigm, pivotal developmental events can be correlated with particular changes from one constellation of gene interactions (...) to a different one, and the method allows the identification of certain network motifs that are not identifiable using static approaches. Features article: “Dynamic network rewiring determines temporal regulatory functions in the Drosophila melanogaster development processes”, see pages 505 – 513. (shrink)

This paper explores how an evolutionary process can produce systems that learn. A general framework for the evolution of learning is outlined, and is applied to the task of evolving mechanisms suitable for supervised learning in single-layer neural networks. Dynamic properties of a network’s information-processing capacity are encoded genetically, and these properties are subjected to selective pressure based on their success in producing adaptive behavior in diverse environments. As a result of selection and genetic recombination, various successful learning mechanisms (...) evolve, including the well-known delta rule. The effect of environmental diversity on the evolution of learning is investigated, and the role of different kinds of emergent phenomena in genetic and connectionist systems is discussed. (shrink)

One of the most profound insights of the dynamic systems perspective is that new structures resulting from the developmental process do not need to be planned in advance, nor is it necessary to have these structures represented in genetic or neurological templates prior to their emergence. Rather, new structures can emerge as components of the individual and the environment self-organize; that is, as they mutually constrain each other's actions, new patterns and structures may arise. This theoretical possibility brings into (...) developmental theory the important concept of indeterminism--the possibility that developmental outcomes may not be predictable in any simple linear causal way from their antecedents. This is the first book to take a critical and serious look at the role of indeterminism in psychological and behavioral development. * What is the source of this indeterminism? * What is its role in developmental change? * Is it merely the result of incomplete observational data or error in measurement? It reviews the concepts of indeterminism and determinism in their historical, philosophical, and theoretical perspectives--particularly in relation to dynamic systems thinking--and applies these general ideas to systems of nonverbal communication. Stressing the indeterminacy inherent to symbols and meaning making in social systems, several chapters address the issue of indeterminism from metaphorical, modeling, and narrative perspectives. Others discuss those indeterministic processes within the individual related to emotional, social, and cognitive development. (shrink)

Polo‐like kinase 1 (PLK1) is a serine/threonine kinase that plays multiple and essential roles during the cell division cycle. Its inhibition in cultured cells leads to severe mitotic aberrancies and cell death. Whereas previous reports suggested that Plk1 depletion in mice leads to a non‐mitotic arrest in early embryos, we show here that the bi‐allelic Plk1 depletion in mice certainly results in embryonic lethality due to extensive mitotic aberrations at the morula stage, including multi‐ and mono‐polar spindles, impaired chromosome segregation (...) and cytokinesis failure. In addition, the conditional depletion of Plk1 during mid‐gestation leads also to severe mitotic aberrancies. Our data also confirms that Plk1 is completely dispensable for mitotic entry in vivo. On the other hand, Plk1 haploinsufficient mice are viable, and Plk1‐heterozygous fibroblasts do not harbor any cell cycle alterations. Plk1 is overexpressed in many human tumors, suggesting a therapeutic benefit of inhibiting Plk1, and specific small‐molecule inhibitors for this kinase are now being evaluated in clinical trials. Therefore, the different Plk1 mouse models here presented are a valuable tool to reexamine the relevance of the mitotic kinase Plk1 during mammalian development and animal physiology. (shrink)

There is growing interest in the evolutionary dynamics of molecular genetic pathways and networks, and the extent to which the molecular evolution of a gene depends on its position within a pathway or network, as well as over‐all network topology. Investigations on the relationships between network organization, topological architecture and evolutionary dynamics provide intriguing hints as to how networks evolve. Recent studies also suggest that genetic pathway and network structures may influence the action of evolutionary forces, (...) and may play a role in maintaining phenotypic robustness in organisms. BioEssays 26:479–484, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Actin is a key protein in numerous cellular functions. One recent study has identified a large set of genes, associated with the actin cytoskeleton, which could be grouped into a wide spectrum of cytoplasmic and nuclear functions, such as protein biosynthesis and gene transcription.1 Deletions of many of the identified genes affected cellular actin organization,1 suggesting a functional link between different actin fractions probably regulated through changes in actin dynamics. The data are very exciting; speculations on the crosstalk between (...) cytoplasmic and nuclear actin fractions in different cellular contexts may help placing the results in perspective to further understand how actin‐mediated signalling affects cellular functions, such as gene expression. BioEssays 29:407–411, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

It is widely accepted that the way information transfers across networks depends importantly on the structure of the network. Here, we show that the mechanism of information transfer is crucial: in many respects the effect of the specific transfer mechanism swamps network effects. Results are demonstrated in terms of three different types of transfer mechanism: germs, genes, and memes. With an emphasis on the specific case of transfer between sub-networks, we explore both the dynamics of each of these across (...) networks and a measure of their comparative fitness. Germ and meme transfer exhibit very different dynamics across linked networks. For germs, measured in terms of time to total infection, network type rather than degree of linkage between sub-networks is the primary factor. For memes or belief transfer, measured in terms of time to consensus, it is the opposite: degree of linkage trumps network type in importance. The dynamics of genetic information transfer is unlike either germs or memes. Transfer of genetic information is robust across network differences to which both germs and memes prove sensitive. We also consider function: how well germ, gene, and meme transfer mechanisms can meet their respective objectives of infecting the population, mixing and transferring genetic information, and spreading a message. A shared formal measure of fitness is introduced for purposes of comparison, again with an emphasis on linked sub-networks. Meme transfer proves superior to transfer by genetic reproduction on that measure, with both memes and genes superior to infection dynamics across all networks types. What kinds of network structure optimize fitness also differ among the three. Both germs and genes show fairly stable fitness with added links between sub-networks, but genes show greater sensitivity to the structure of sub-networks at issue. Belief transfer, in contrast to the other two, shows a clear decline in fitness with increasingly connected networks. When it comes to understanding how information moves on networks, our results indicate that questions of information dynamics on networks cannot be answered in terms of networks alone. A primary role is played by the specific mechanism of information transfer at issue. We must first ask about how a particular type of information moves. (shrink)

How will the adoption of genetically modified staple crops reconfigure labor processes in Sub-Saharan Africa? This article focuses on Uganda, where GM varieties of matooke, the country’s primary carbohydrate staple, are expected to be commercialized within the next few years. The paper draws on survey data and focus groups with a random sample of over one hundred and fifty growers to investigate the potential ways a variety engineered to be resistant to banana bacterial wilt might impact labor dynamics. A (...) BBW resistant GM variety will displace labor currently allocated to disease prevention and control, and increase the labor required for harvesting higher yields. How farmers can address the need for more harvesting labor varies significantly according to region. In the southwestern highlands, producers can increase their portion of hired labor. In the central and eastern regions, where farms tend to be smaller and subsistence-oriented, farmers are more likely to intensify their use of unpaid family labor, particularly that of wives. Hence, while GM technology may result in increased yields for small-scale farmers in Uganda, this is likely to come at the cost of intensifying the agricultural labor burdens of women in the central and eastern region. (shrink)

The recent expansion of online genetic-genealogical networks has been hailed as a development that could break racial taboos in the United States by providing irrefutable evidence of the myriad historical and genetic links—many originating in slavery—connecting white and black families. These predictions are countered, however, by a scholarly literature on “white ignorance,” defined as an active historical project that works to prevent privileged groups from apprehending their links to, and positionality within, systems of racial oppression. This paper mobilizes (...) concepts from the fields of agnotology and epistemic ethics to assess how far genetic-genealogical technologies can contribute to redressing racialized epistemic inequities between slave and slaveholder descendants, by inducing the latter to respond to the former’s kinship claims and give access to data that could help reconstruct their linked family histories. Drawing on ethnographic and interview data that foreground the experiences of African American genealogists, the study outlines the structural and affective dimensions that have converged to enable white ignorance regarding genealogies of slavery and discusses ethical and technical solutions proposed by genealogical practitioners to redress the racialized power dynamics that continue to condition access to, and public acceptance of, family history knowledge relating to slavery. (shrink)

This paper presents methods to visualize the structure of trees that occur in genetic programming. These methods allow for the inspection of structure of entire trees even though several thousands of nodes may be involved. The methods also scale to allow for the inspection of structure for entire populations and for complete trials even though millions of nodes may be involved. Examples are given that demonstrate how this new way of “seeing” can afford a potentially rich way of understanding (...) dynamics that underpin genetic programming. The examples indicate further studies that might be enabled by visualizing structure at these scales. (shrink)

This volume reflects on the effects of recent discoveries in genetics on a broad range of scientific fields. In addition to neuroscience, evolutionary biology, anthropology and medicine, contributors analyze the effects of genetics on theories of health, law, epistemology and philosophy of biology. Social and moral concerns about the relationship between genetics, society and the individual also figure prominently. Genetic discoveries fuel central contemporary public policy debates concerning, for example, human cloning, equitable access to healthcare or the role of (...) genetics in medicine. Perhaps more fundamentally, advances in genetics are altering our perception of human life and death. An interview with François Jacob by Anne Fagot-Largeault opens the volume. In this interview, Jacob, who shared a Nobel Prize with André Lwoff and Jacques Monod for their discoveries concerning genetic control of enzyme and virus synthesis, addresses many of the central methodological epistemological and ethical questions covered in the volume. The dynamic interdisciplinary character of this volume makes it relevant to scholars from many disciplines, from biology, philosophy and the social sciences. (shrink)

We formulate the following hypothesis: Life's origin may have occurred during the lower Archaean at a time when the environmental temperature was higher than it is at present. Preliminary consequences of this hypothesis are studied from the point of view of molecular evolution. We restrict our attention to implications regarding the genetic code. We conclude that alternative assignment of termination codons may be understood in terms of: (a) the elevated temperatures to which the progenote may initially have been exposed; (...) and (b) the subsequent response of its genome to the opportunity provided by the eventual loss of hyperthermal genetic expression during a thermal transition (TT) period, which was triggered off by the evolution of the dynamic Earth. (shrink)

This paper provides a marketing ethics analysis that addresses the practice of selling genetic tests directly to the consumer. It details the complexity of this emergent sector by articulating the panoply of evolving ethical/social questions raised by this development. It advances the conversation about DTC genetic testing by reviewing the business and healthcare literature concerning this topic and by laying out the inherent ethical complications for consumers, marketers, and regulators. It also points to several possible public and company (...) policy adjustments. Because this area is relatively new and incredibly dynamic, its current discussion is necessarily an exercise in the “logic of discovery” rather than the “protocol of validation”. The paper serves as a primer for the types of GT being promoted. It also calls for a public discourse in the academic and general community to uncover and define the ethical guidelines and systemic adjustments necessary to create fairness in the various DTC transactions occurring between genetic test sellers and the buyers/clients of their services. (shrink)

We present a new viable nonlinear chaotic paradigm. This paradigm has four nonlinear terms. The essential features of the new paradigm have been investigated. Our new system is confirmed to have chaotic behaviors by calculating its Lyapunov exponents. The relations of the system states are displayed by a suggested new signal flow graph. The proposed SFG is discussed via some graph theory tools, and some of its hidden features are calculated. In addition, the system is realized via constructing its electronic (...) circuit which helps in the real applications. Also, a robust controller for the system is designed with the aid of a genetic algorithm. (shrink)

How did molecules become signs? First, according to Deacon, there had to be an interpreter, a physical process capable of making use of some property of a molecule that offered a “semiotic affordance.” He proposes the model of an “autogenic virus,” the most primitive conceivable recursively self-maintaining kind of molecular system that could broach the boundary between physico-chemical process and “interpretive competence.” In this comment I work up to the question of how Deacon introduces concepts such as “representation” and “record” (...) into his account, to argue that the autogen can pass on its lineage without a genetic template. (shrink)