Three-legged animals do not exist today and such an animal is not found in the fossil record. Which constraints operate to result in the lack of a triped phenotype? Consideration of animal locomotion and robotic studies suggests that physical constraints would not prevent a triped from being functional or advantageous. As is reviewed here, the strongest constraint on the evolution of a triped is phylogenetic: namely, the early genetic adoption of a bilaterally symmetrical body plan occurring before the advent of (...) limbs. Presumably, this would greatly constrain any three-legged animal from ever evolving. Tripedalism is employed only by a few animals, but many use a tripod stance while engaged in a variety of activities. Because terms are often used interchangeably in the literature, a standardization of locomotion terminology is proposed. Understanding the constraints behind “forbidden” phenotypes forces us to confront gaps in our evolutionary understanding of which we may be unaware. (shrink)

Phenotypic Evolution explicitly recognizes organisms as complex genetic-epigenetic systems developing in response to changing internal and external environments. As a key to a better understanding of how phenotypes evolve, the authors have developed a framework that centers on the concept of the Developmental Reaction Norm. This encompasses their views: (1) that organisms are better considered as integrated units than as disconnected parts (allometry and phenotypic integration); (2) that an understanding of ontogeny is vital for evaluating evolution of adult forms (...) (ontogenetic trajectories, epigenetics, and constraints); and (3) that environmental heterogeneity is ubiquitous and must be acknowledged for its pervasive role in phenotypic expression. (shrink)

Phenotypic plasticity integrates the insights of ecological genetics, developmental biology, and evolutionary theory. Plasticity research asks foundational questions about how living organisms are capable of variation in their genetic makeup and in their responses to environmental factors. For instance, how do novel adaptive phenotypes originate? How do organisms detect and respond to stressful environments? What is the balance between genetic or natural constraints (such as gravity) and natural selection? The author begins by defining phenotypic plasticity and detailing its history, (...) including important experiments and methods of statistical and graphical analysis. He then provides extended examples of the molecular basis of plasticity, the plasticity of development, the ecology of plastic responses, and the role of costs and constraints in the evolution of plasticity. A brief epilogue looks at how plasticity studies shed light on the nature/nurture debate in the popular media. (shrink)

The Forbidden Subject launches from Ed Abbey's affirmation in Desert Solitaire: 'This is the most beautiful place on earth'. How could such a sentiment become construed as problematic, elitist, or worse? How did beauty become, and why does it largely remain, what Emory Elliot dubbed 'the forbidden subject'?

In a now classic paper published in 1991, Alberch introduced the concept of genotype–phenotype (G!P) mapping to provide a framework for a more sophisticated discussion of the integration between genetics and developmental biology that was then available. The advent of evo-devo first and of the genomic era later would seem to have superseded talk of transitions in phenotypic space and the like, central to Alberch’s approach. On the contrary, this paper shows that recent empirical and theoretical advances have only sharpened (...) the need for a different conceptual treat- ment of how phenotypes are produced. Old-fashioned metaphors like genetic blueprint and genetic programme are not only woefully inadequate but positively misleading about the nature of G!P, and are being replaced by an algorithmic approach emerging from the study of a variety of actual G!P maps. These include RNA folding, protein function and the study of evolvable soft- ware. Some generalities are emerging from these disparate fields of analysis, and I suggest that the concept of ‘developmental encoding’ (as opposed to the classical one of genetic encoding) provides a promising computational–theoretical underpinning to coherently integrate ideas on evolvability, modularity and robustness and foster a fruitful framing of the G!P mapping problem. (shrink)

I examine an objection against autonomy-minded liberalism sometimes made by philosophers such as John Rawls and William Galston, that it rules out ways of life which do not themselves value freedom or autonomy. This objection is incorrect, because one need not value autonomy in order to live an autonomous life. Hence autonomy-minded liberalism need not rule out such ways of life. I suggest a modified objection which does work, namely that autonomy-minded liberalism must rule out ways of life that could (...) not develop under an autonomy-promoting education. I conclude by suggesting some reasons why autonomy-minded liberals should bite the bullet and accept this. (shrink)

Phenotype, whether conventional or extended, is defined as a reflectionof an underlying genotype. Adaptation and the natural selection thatfollows from it depends upon a progressively harmonious fit betweenphenotype and environment. There is in Richard Dawkins' notion ofthe extended phenotype a paradox that seems to undercut conventionalviews of adaptation, natural selection and adaptation. In a nutshell, ifthe phenotype includes an organism's environment, how then can theorganism adapt to itself? The paradox is resolvable through aphysiological, as opposed to a genetic, theory of (...) natural selection andadaptation. (shrink)

Certain research strands can yield “forbidden knowledge”. This term refers to knowledge that is considered too sensitive, dangerous or taboo to be produced or shared. Discourses about such publication restrictions are already entrenched in scientific fields like IT security, synthetic biology or nuclear physics research. This paper makes the case for transferring this discourse to machine learning research. Some machine learning applications can very easily be misused and unfold harmful consequences, for instance, with regard to generative video or text (...) synthesis, personality analysis, behavior manipulation, software vulnerability detection and the like. Up till now, the machine learning research community embraces the idea of open access. However, this is opposed to precautionary efforts to prevent the malicious use of machine learning applications. Information about or from such applications may, if improperly disclosed, cause harm to people, organizations or whole societies. Hence, the goal of this work is to outline deliberations on how to deal with questions concerning the dissemination of such information. It proposes a tentative ethical framework for the machine learning community on how to deal with forbidden knowledge and dual-use applications. (shrink)

The book explores the forbidden feelings of beauty, admiration, or satisfaction before instances of terror and human pain from eighteenth-century natural disasters to twenty-first-century terrorist destruction. It explores the fascination felt by the subject witnessing major disasters directly or in a mediated fashion. Emmanouil Aretoulakis' makes the challenging proposition that there is, paradoxically, an ethics in the aesthetic appraisal of terror.

Some claim that digital phenotyping will revolutionize understanding of human psychology and experience and significantly promote human wellbeing. This paper investigates the nature of digital phenotyping in relation to its alleged promise. Unlike most of the literature to date on philosophy and digital phenotyping, which has focused on its ethical aspects, this paper focuses on its epistemic and methodological aspects. The paper advances a tetra-taxonomy involving four scenario types in which knowledge may be acquired from human “digitypes” by digital phenotyping. (...) These scenarios comprise two causal relations and a correlative and constitutive relation that can exist between information generated by digital systems/devices on the one hand and psychological or behavioral phenomena on the other. The paper describes several modes of inference involved in deriving knowledge within these scenarios. After this epistemic mapping, the paper analyzes the possible knowledge potential and limitations of digital phenotyping. It finds that digital phenotyping holds promise of delivering insight into conditions and states as well producing potentially new psychological categories. It also argues that care must be taken that digital phenotyping does not make unwarranted conclusions and is aware of potentially distorting effects in digital sensing and measurement. If digital phenotyping is to truly revolutionize knowledge of human life, it must deliver on a range of fronts, including making accurate forecasts and diagnoses of states and behaviors, providing causal explanations of these phenomena, and revealing important constituents of human conditions, psychology, and experience. (shrink)

Co-creating knowledge takes a new approach to human phenotypic morality as a biologically based, human lineage specific trait. Authors from very different backgrounds first review research on the nature and origins of morality using the social brain network, and studies of individuals who cannot “know good” or think morally because of brain dysfunction. They find these models helpful but insufficient, and turn to paleoanthropology, cognitive science, and neuroscience to understand human moral capacity and its origins long ago, in the genus (...) Homo. An unusual narrative capturing “morality in action” takes the reader back 900,000 years, and then the authors analyze the essential features of moral thinking and behavior as expressed by early and later species on our lineage. In what has primarily been the province of philosophers to date, the authors’ morality model is presented for further scientific testing. (shrink)

An exploration of the nexus between ecology, evolutionary biology and molecular biology, via the concept of phenotypic plasticity.

[Introduction]: Curiosity is now widely regarded, with some justification, as a vital ingredient of the inquiring mind and, more particularly, as a crucial virtue for the practitioner of the pure sciences. We have become accustomed to associate curiosity with innocence and, in its more mature manifestations, with the pursuit of truth for its own sake. It was not always so. The sentiments expressed in Sir John Davies's poem, published on the eve of the seventeenth century, paint a somewhat different picture. (...) To seek knowledge with no particular end in mind was to indulge in "fruitlesse curiositie," while the "desire to know" was associated with those catastrophic events that took place at the dawn of history in the Garden of Eden and with the ensuing curse that fell upon succeeding generations. Davies's poem neatly sets out two of the chief impediments to the advancement of learning in seventeenth-century England: the fact that the Genesis narrative attributes the Fall of the human race to the desire for knowledge, and the moral disapprobation associated with the vice of curiosity. In short, the traditional classification of curiosity amongst the vices and its complicity in the commission of the first sin represented a major obstacle to early modern projects to enlarge human learning. This essay will explore the changing fortunes of curiosity, from its construction as an intellectual vice in the patristic era to its subsequent transformation, over the course of the seventeenth century, to a virtue. Particular attention will be paid to the way in which Francis Bacon dealt with prevailing conceptions of curiosity and forbidden knowledge and how he modified an existing view of the moral legitimacy of knowledge of nature in order to provide rhetorical justification for his proposed instauration of learning. This change in the status of knowledge of nature, initiated by Bacon and promoted by his successors, highlights the morally charged character of early modem debates over the status of natural philosophy and the particular virtues required of its practitioners. As we shall see, the rehabilitation of curiosity was a crucial element in the objectification of scientific knowledge and led to a shift of focus away from the moral qualities of investigators and the propriety of particular objects of knowledge to specific disciplines, procedures, and methods. (shrink)

Let $\mathscr {C}$ be a class of finite and infinite graphs that is closed under induced subgraphs. The well-known Łoś–Tarski Theorem from classical model theory implies that $\mathscr {C}$ is definable in first-order logic by a sentence $\varphi $ if and only if $\mathscr {C}$ has a finite set of forbidden induced finite subgraphs. This result provides a powerful tool to show nontrivial characterizations of graphs of small vertex cover, of bounded tree-depth, of bounded shrub-depth, etc. in terms of (...) forbidden induced finite subgraphs. Furthermore, by the Completeness Theorem, we can compute from $\varphi $ the corresponding forbidden induced subgraphs. This machinery fails on finite graphs as shown by our results: – There is a class $\mathscr {C}$ of finite graphs that is definable in first-order logic and closed under induced subgraphs but has no finite set of forbidden induced subgraphs. – Even if we only consider classes $\mathscr {C}$ of finite graphs that can be characterized by a finite set of forbidden induced subgraphs, such a characterization cannot be computed from a first-order sentence $\varphi $ that defines $\mathscr {C}$ and the size of the characterization cannot be bounded by $f(|\varphi |)$ for any computable function f. Besides their importance in graph theory, the above results also significantly strengthen similar known theorems for arbitrary structures. (shrink)

Since the idea of forbidden knowledge is rooted in the biblical story of Adam and Eve eating from the forbidden tree of knowledge, its meaning today, in particular as a metaphor for scientific knowledge, is not so obvious. We can and should ask questions about the autonomy of science.

The problem of the existence of a universal structure omitting a finite set of forbidden substructures is reducible to the corresponding problem in the category of graphs with a vertex coloring by two colors. It is not known whether this problem reduces further to the category of ordinary graphs. It is also not known whether these problems are decidable.

Phenotypic integration refers to the study of complex patterns of covariation among functionally related traits in a given organism. It has been investigated throughout the 20th century, but has only recently risen to the forefront of evolutionary ecological research. In this essay, I identify the reasons for this late flourishing of studies on integration, and discuss some of the major areas of current endeavour: the interplay of adaptation and constraints, the genetic and molecular bases of integration, the role of phenotypic (...) plasticity, macroevolutionary studies of integration, and statistical and conceptual issues in the study of the evolution of complex phenotypes. I then conclude with a brief discussion of what I see as the major future directions of research on phenotypic integration and how they relate to our more general quest for the understanding of phenotypic evolution within the neo-Darwinian framework. I suggest that studying integration provides a particularly stimulating and truly interdisciplinary convergence of researchers from fields as disparate as molecular genetics, developmental biology, evolutionary ecology, palaeontology and even philosophy of science. (shrink)

A new voice in the nature-nurture debate can be heard at the interface between evolution and development. Phenotypic integration is a major growth area in research.

This chapter considers epistemology to look at the four sorcerers who were once students of the Ancient One: Jonathan Pangborn, Kaecilius, Mordo, and Doctor Stephen Strange. In the 2016 film Doctor Strange, the Book of Cagliostro is a repository of forbidden knowledge of dark magic. The notion of “forbidden knowledge” is deeply ingrained in the collective consciousness. By contrast to the practicality of reliabilism, responsibilism emphasizes the ethical aspect of the acquisition of knowledge, demanding not only that it (...) be acquired well but virtuously. According to contemporary philosopher James Montmarquet, there are three character traits that are conducive to being epistemically virtuous in this sense: impartiality, courage, and the ability to unite these two in proper ways. Though none of the Ancient One's students display perfect intellectual virtue, Doctor Strange ultimately comes closest to the virtues of impartiality and intellectual courage in their proper balance. (shrink)

In addition to considerable debate in the recent evolutionary literature about the limits of the Modern Synthesis of the 1930s and 1940s, there has also been theoretical and empirical interest in a variety of new and not so new concepts such as phenotypic plasticity, genetic assimilation and phenotypic accommodation. Here we consider examples of the arguments and counter- arguments that have shaped this discussion. We suggest that much of the controversy hinges on several misunderstandings, including unwarranted fears of a general (...) attempt at overthrowing the Modern Synthesis paradigm, and some fundamental conceptual confusion about the proper roles of phenotypic plasticity and natural selection within evolutionary theory. (shrink)

This chapter contains section titled: Introduction: What is Phenotypic Plasticity? Developmental Conversion and Developmental Sensitivity: Two Forms of Phenotypic Plasticity Environmental Heterogeneity, Cues, and Plasticity Phenotypic Plasticity and Developmental Buffering The Future of Phenotypic Plasticity Research Acknowledgments References Further Reading.

The great majority of phenotypic characteristics are complex traits, complicating the identification of the genes underlying their expression. However, both methodological and theoretical progress in genome‐wide association studies have resulted in a much better understanding of the underlying genetics of many phenotypic traits, including externally visible characteristics (EVCs) such as eye and hair color. Consequently, it has become possible to predict EVCs from human samples lacking phenotypic information. Predicting EVCs from genetic evidence is clearly appealing for forensic applications involving the (...) personal identification of human remains. Now, a recent paper has reported the genetic determination of eye and hair color in samples up to 800 years old. The ability to predict EVCs from ancient human remains opens up promising perspectives for ancient DNA research, as this could allow studies to directly address archaeological and evolutionary questions related to the temporal and geographical origins of the genetic variants underlying phenotypes. (shrink)

While the field of semiotics has been active since it was started by Peirce, it appears like the last decade has been especially productive with a number of important new concepts being developed within the biosemiotics community. The novel concept of the Semiotic scaffold by Hoffmeyer is an important addition that offers insight into the hardware requirements for bio-semiosis. As any type of semiosis must be dependent upon Semiotic scaffolds, I recently argued that the process of semiosis has to be (...) divided into two separate processes of sign establishment and sign interpretation, and that misalignment between the two processes result in faulty sign interpretation and over-signification. Such faulty signs were forbidden in the sign classification system of Peirce, so I defined them as forbidden signs. Here I present an analysis of the forbidden sign categories with examples from Occult semiotics. I also show that biological semiosis offers examples of forbidden signs, where the faulty interpretation of signs may lead to decimation of whole evolutionary lines of organisms. A new concept of Evolutionary memory which is applicable to both human and biological semiosis is explained as the combination of two processes; one leading to diversity generation within semiotic scaffolds followed by a second process of decimation of faulty signs during selection in specific learning environments. The analysis suggests that forbidden signs are always used as early stages in the iterative sign establishment process during semiosis. (shrink)

Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress (...) that has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility. (shrink)

Hyperplasia and hypertrophy are elements of phenotypic plasticity adjusting organ size and function. Because they are costly, we assume that they are beneficial. In this review, the authors discuss examples of tissue and organ systems that respond with plastic changes to osmotic stress to raise awareness that we do not always have sufficient experimental evidence to conclude that such processes provide fitness advantages. Changes in hydranth architecture in the hydroid Cordylophora caspia or variations in size in the anal papillae of (...) insect larvae upon changes in medium salinity may be adaptive or not. The restructuring of salt glands in ducklings upon salt‐loading is an example of phenotypic plasticity which indeed seems beneficial. As the genomes of model species are recently sequenced and the animals are easy to rear, these species are suitable study objects to investigate the biological significance of phenotypic plasticity and to study potential epigenetic and other mechanisms underlying phenotypic changes. (shrink)

Mathematical modeling can ground communication and reciprocal enrichment among fields of knowledge whose domains are very different. We propose a new mathematical model applicable in biology, specified into ecology and evolutionary biology, and in cultural transmission studies, considered as a branch of economics. Main inspiration for the model are some biological concepts we call “eco-phenotypic” such as development, plasticity, reaction norm, phenotypic heritability, epigenetics, and niche construction. “Physiology” is a core concept we introduce and translate differently in the biological and (...) cultural domains. The model is ecological in that it aims at describing and studying organisms and populations that perform living, intended as a thermodynamic, matter-energy process concerning resources gathering, usage, and depletion in a spatiotemporal context with given characteristics, as well as with multiplication and space occupation. The model also supports evolution, intended as a dynamics including cumulative change in the features of unique organisms that are connected into breeding populations. The model is then applicable to the economics of cultural transmission in which individuals form their attitudes and patterns of behavior under a complex system of influences derived from their “cultural parents”, other members of the society, and the environment. On the side of biology, an innovative goal is to integrate in a single model all the eco-phenotypic concepts as well as both evolution and ecology. On the side of cultural transmission, eco-phenotypic modeling seems more appropriate in capturing some aspects of cultural systems which are modeled away in the earlier framework based on Mendelian population genetics. (shrink)

In recent years philosophers have attempted to clarify the units of selection controversy in evolutionary biology by offering conceptual analyses of the term 'unit of selection'. A common feature of many of these analyses is an emphasis on the claim that units of selection are entities exhibiting heritable variation in fitness. In this paper I argue that the demand that units of selection be characterized in terms of heritability is unnecessary, as well as undesirable, on historical, theoretical, and philosophical grounds. (...) I propose a positive account of the proper referent of the term 'unit of selection', distinguishing between the processes of evolution and phenotypic selection. The main result of this analysis is greater clarity about the conceptual structure of evolutionary theory. (shrink)

The narrative of the digital phenotype as a transformative vector in healthcare is nearly identical to the concept of “data drivenness” in other fields such as law enforcement. We examine the role of a prescription drug monitoring program in California—a computerized law enforcement surveillance program enabled by a landmark Supreme Court case that upheld “broad police powers”—in the interprofessional conflict between physicians and law enforcement over the jurisdiction of drug use. We bring together interview passages, clinical artifacts, and academic and (...) gray literature to investigate the power relations between police, physicians, and patients to show that prescribing data appear to the physician as evidence of problematic patient behavior by the patients, and to law enforcement as evidence of physician misconduct. In turn, physicians have adopted a disciplinary approach to patients, using quasi-legalistic documents to litigate patient behavior. We conclude that police powers have been used to pave data infrastructure through a contested jurisdiction, and law enforcement have used that infrastructure to enroll physicians into the work of disciplining patients. (shrink)

This book examines the concept of "forbidden knowledge" in religion, science, government, and psychology. From the tree of knowledge in the Garden of Eden (forbidden fruit), to world altering scientific research (nuclear power, stem-cells, cloning) to damning government secrets (Abu Ghraib, domestic spying), to traumatic experiences that individuals want to repress (sexual abuse), humanity has encountered knowledge that has been hidden and suppressed. We experience this denial as a loss of control and respect, and we want to know (...) exactly what knowledge has been prohibited and why we cannot have access to it. The author takes the general position that too much material is prohibited, especially today, even while business and government invade individual privacy more and more. A primary assumption in a democracy is that we can have confidence in the people, so information should not be forbidden unless there is a vital and compelling reason to withhold it. (shrink)

The ‘phenotypic gambit,’ the assumption that we can ignore genetics and look at the fitness of phenotypes to determine the expected evolutionary dynamics of a population, is often used in evolutionary game theory. However, as this paper will show, an overlooked genotype to phenotype map can qualitatively affect evolution in ways the phenotypic approach cannot predict or explain. This gives us reason to believe that, even in the long-term, correspondences between phenotypic predictions and dynamical outcomes are not robust for (...) all plausible assumptions regarding the underlying genetics of traits. This paper shows important ways in which the phenotypic gambit can fail and how to proceed with evolutionary game theoretic modeling when it does. (shrink)

In The Selfish Gene, Richard Dawkins crystallized the gene's eye view of evolution developed by W.D. Hamilton and others. The book provoked widespread and heated debate. Written in part as a response, The Extended Phenotype gave a deeper clarification of the central concept of the gene as the unit of selection; but it did much more besides. In it, Dawkins extended the gene's eye view to argue that the genes that sit within an organism have an influence that reaches out (...) beyond the visible traits in that body - the phenotype - to the wider environment, which can include other individuals. So, for instance, the genes of the beaver drive it to gather twigs to produce the substantial physical structure of a dam; and the genes of the cuckoo chick produce effects that manipulate the behaviour of the host bird, making it nurture the intruder as one of its own. This notion of the extended phenotype has proved to be highly influential in the way we understand evolution and the natural world. It represents a key scientific contribution to evolutionary biology, and it continues to play an important role in research in the life sciences. The Extended Phenotype is a conceptually deep book that forms important reading for biologists and students. But Dawkins' clear exposition is accessible to all who are prepared to put in a little effort. Oxford Landmark Science books are 'must-read' classics of modern science writing which have crystallized big ideas, and shaped the way we think. (shrink)

The paper describes the context and the origin of a particular debate that concerns the evolution of phenotypic plasticity. In 1965, British biologist A. D. Bradshaw proposed a widely cited model intended to explain the evolution of norms of reaction, based on his studies of plant populations. Bradshaw’s model went beyond the notion of the “adaptive norm of reaction” discussed before him by Dobzhansky and Schmalhausen by suggesting that “plasticity” the ability of a phenotype to be modified by the environment (...) should be genetically determined. To prove Bradshaw’s hypothesis, it became necessary for some authors to identify the pressures exerted by natural selection on phenotypic plasticity in particular traits, and thus to model its evolution. In this paper, I contrast two different views, based on quantitative genetic models, proposed in the mid-1980s: Russell Lande and Sara Via’s conception of phenotypic plasticity, which assumes that the evolution of plasticity is linked to the evolution of the plastic trait itself, and Samuel Scheiner and Richard Lyman’s view, which assumes that the evolution of plasticity is independent from the evolution of the trait. I show how the origin of this specific debate, and different assumptions about the evolution of phenotypic plasticity, depended on Bradshaw’s definition of plasticity and the context of quantitative genetics. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:The Phenotype/Genotype Distinction and the Disappearance of the BodyGabriel GuddingThe discipline of genetics has long been a rhetorical and heuristic locus for social and political issues. As such, the science has influenced culture through the avenues of law, medicine, warfare, social work, and even, since 1972 in California, the education of kindergarten students. It has affected how we view the body, morality, romance, biography, and agency—not to mention procreation (...) and death.In many ways the delamination of genotype from phenotype was the first cut, so to speak, in this new cosmetics of life. The distinction between structure and expression arose from an interdisciplinary struggle for authority in the biological sciences at the turn of the century. This preceptual split in the organism between structure and expression came over time to fundamentally alter the percepts of the body, in terms of how the body is juridically, medicinally, and otherwise, generally perceived and understood. More importantly and interestingly, this delamination within the organism between its genotype and phenotype eventually led to a sense of the body’s fragility and its eventual “disappearance” as a seat of agency, morality, and identity; and in turn these three groundings of modernity have been redistributed to the gene, the genotype, and the genome. In one sense, then, this paper traces not so much the birth of a new view of the body (the genetic) but the drama of its disappearance, in which the body melts to a silhouette and is replaced by the genotype and its expression, the phenotype.In 1911 Wilhelm Johannsen of the University of Copenhagen published “The Genotype Conception of Heredity,” 1 which introduced to geneticists the ideas of “phenotype” and “genotype.” Johannsen coined these terms in objection to what he considered to be an erroneous conception of heredity, [End Page 525] which he called the “transmission view”: the idea that “personal qualities” (such as honesty or good looks) could themselves be or otherwise influence “the true heritable elements or traits” passed on from one generation to another. He called this transmission view “apparent heredity” and claimed that this idea relied upon an economic-juridical model of the transmission of property—and thereby provided no disciplined or profound understanding of true heredity. He asserted that in factthe transmission-conception of heredity represents exactly the reverse of the real facts, just as the famous Stahlian theory of “phlogiston” was an expression diametrically opposite to the chemical reality. The personal qualities of any individual organism do not at all cause the qualities of its offspring; but the qualities of both ancestor and descendent are in quite the same manner determined by the nature of the “sexual substances”—i.e., the gametes—from which they have developed. Personal qualities are then the reactions of the gametes joining to form a zygote; but the nature of the gametes is not determined by the personal qualities of the parents or ancestors in question. This is the modern view of heredity. 2This was indeed a profoundly new view of heredity: Johannsen quite boldly and deliberately intended his genotype-phenotype distinction to stand as a watershed between the old science of heredity—exemplified by Mendel, Galton, Weismann, and others—and the new science of genetics. He said, “The science of genetics is in a transition period, becoming an exact science just as the chemistry in the times of Lavoisier, who made the balance an indispensable implementation in chemical research.” 3 And he was right: genetics was indeed in a transition period, primarily due to the theoretically accommodating qualities of this new distinction. The science of genetics became radically simplified: the confusion which arose from the attempts to correlate characteristics to their corresponding units of hereditarian influence diminished. Viewing personal qualities and characteristics, in all their variation, as expressions of underlying structures instead of mutual correlates to them drastically simplified the theoretical and experimental aspects of heredity.Not only did this distinction revolutionize the science of heredity, it helped insinuate the new science of genetics into a position of autonomy and authority with respect to the other life sciences. Historians of science, such as Jan Sapp, have suggested that the genotype-phenotype distinction played a... (shrink)

Predicting the phenotype of an organism from its genotype is a central question in genetics. Most importantly, we would like to find out if the perturbation of a single gene may be the cause of a disease. However, our current ability to predict the phenotypic effects of perturbations of individual genes is limited. Network models of genes are one tool for tackling this problem. In a recent study, (Lee et al.) it has been shown that network models covering the majority (...) of genes of an organism can be used for accurately predicting phenotypic effects of gene perturbations in multicellular organisms. BioEssays 30:707–710, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Selection operates at many levels. Some of the most obvious cases are organismic, such as changes in coloration under the influence of predation (cf. Kettlewell 1973; also Endler 1986). It also operates at other levels. Meiotic drive involves selection for a gene, independently of its effect on the organism. At a higher level, there may also be selection for patterns of colony growth in social insects, again under the influence of predation (cf. Wilson 1971). The appropriate level of selection is (...) a matter of the causal patterns exhibited, or the target of selection. It can also be understood as a question of the appropriate level at which to seek explanatory laws.Robert Brandon (1982, 1990) first clearly distinguished the question of the level of selection from debates over the units of selection. In doing so, he argued that the phenotype is commonly the target of selection, whatever the unit of selection might be. (shrink)

Selection operates at many levels. Robert Brandon has distinguished the question of the level of selection from the unit of selection, arguing that the phenotype is commonly the target of selection, whatever the unit of selection might be. He uses "screening off" as a criterion for distinguishing the level of selection. Cave animals show a common morphological pattern which includes hypertrophy of some structures and reduction or loss of others. In a study of a cave dwelling crustacean, Gammarus minus, we (...) find evidence for selection for both increased antennal size and reduction of eyes. The genetic structure of the population does not support the view that the phenotype screens off the genotype in explaining the differences in fitness. Nonetheless, the results do indicate that the level of selection is at least at the level of the phenotype in both cases. (shrink)

Autism Spectrum Disorder (ASD) is extremely heterogeneous clinically and genetically. There is a pressing need for a better understanding of the heterogeneity of ASD based on scientifically rigorous approaches centered on systematic evaluation of the clinical and research utility of both phenotype and genotype markers. This paper presents a holistic PheWAS-inspired method to identify meaningful associations between ASD phenotypes and genotypes. We generate two types of phenotype-phenotype (p-p) graphs: a direct graph that utilizes only phenotype data, and an indirect (...) graph that incorporates genotype as well as phenotype data. We introduce a novel methodology for fusing the direct and indirect p-p networks in which the genotype data is incorporated into the phenotype data in varying degrees. The hypothesis is that the heterogeneity of ASD can be distinguished by clustering the p-p graph. The obtained graphs are clustered using network-oriented clustering techniques, and results are evaluated. The most promising clusterings are subsequently analyzed for biological and domain-based relevance. Clusters obtained delineated different aspects of ASD, including differentiating ASD-specific symptoms, cognitive, adaptive, language and communication functions, and behavioral problems. Some of the important genes associated with the clusters have previous known associations to ASD. We found that clusters based on integrated genetic and phenotype data were more effective at identifying relevant genes than clusters constructed from phenotype information alone. These genes included five with suggestive evidence of ASD association and one known to be a strong candidate. (shrink)