Here, we propose that the heterogeneity of mutational types in populations underpins alternative pathways of evolutionary adaptation. Point mutations, deletions, insertions, transpositions and duplications cause different biological effects and provide distinct adaptive possibilities. Experimental evidence for this notion comes from the mutational origins of adaptive radiations in large, clonal bacterial populations. Independent sympatric lineages with different phenotypes arise from distinct genetic events including gene duplication, different insertion sequence movements and several independent point mutations. The breadth of the mutational spectrum in (...) the ancestral population should be viewed as a form of bet‐hedging, reducing the risk of evolutionary dead ends and complementing the phenotypic and epigenetic heterogeneities that improve the survival capabilities of a population. Different mutational events arise from distinct cellular processes and are subject to separate environmental impacts, so the availability of any particular type of mutation may constrain or promote adaptive pathways in populations. (shrink)

:Masculinity studies recognizes that masculinity is culturally variable, historically specific, multidimensional, and multiple. This mutability is reflected in concepts like hegemonic masculinity, hybrid masculinity, mosaic masculinities, personalized masculinities, sensual masculinity, and inclusive masculinity. Building on this idea of mutating masculinity, this paper addresses a theoretical problem acknowledged by many scholars: how to account for both the singular intimacy of lived experience and the commonality of shared social norms. In order to build a mutable model that encompasses both experience and norms (...) the paper borrows from Félix Guattari's technique of schizoanalytic cartography, which maps assemblages. This new approach to theorizing masculinity is illustrated by diagrams which map its institutional, discursive, cultural, existential, bodily, and biological aspects. (shrink)

The Polycomb group of proteins (PcGs) are transcriptional repressor complexes that regulate important biological processes and play critical roles in cancer. Mutating or deleting EZH2 can have both oncogenic and tumor suppressive functions by increasing or decreasing H3K27me3. In contrast, mutations of SUZ12 and EED are reported to have tumor suppressive functions. EZH2 is overexpressed in many cancers, including prostate cancer, which can lead to silencing of tumor suppressors, genes regulating epithelial to mesenchymal transition (EMT), and interferon signaling. In some (...) cases, EZH2 overexpression also leads to its use of non‐histone substrates. Lastly, PRC2 associated factors can influence the progression of cancer through progressive mutations or by specific binding to certain target genes. Here, we discuss which mutations and deletions of the PRC2 complex have been detected in different cancers, with a specific focus on the overexpression of EZH2 in prostate cancer. (shrink)

One central tenet of the Modern Evolutionary Synthesis , and the consensus view among biologists until now, is that all genetic mutations occur by “chance” or at “random” with respect to adaptation. However, the discovery of some molecular mechanisms enhancing mutation rate in response to environmental conditions has given rise to discussions among biologists, historians and philosophers of biology about the “chance” vs “directed” character of mutations . In fact, some argue that mutations due to a particular kind (...) of mutator mechanisms challenge the Modern Synthesis because they are produced when and where needed by the organisms concerned. This paper provides a defense of the Modern Synthesis’ consensus view about the chance nature of all genetic mutations by reacting to Jablonka and Lamb’s analysis of genetic mutations and the explicit Lamarckian flavor of their arguments. I argue that biologists can continue to talk about chance mutations according to what I call and define as the notion of “evolutionary chance,” which I claim is the Modern Synthesis’ consensus view and a reformulation of Darwin’s most influential idea of “chance” variation. Advances in molecular genetics are therefore significant but not revolutionary with respect to the Modern Synthesis’ paradigm. (shrink)

A widely accepted tenet of evolutionary biology is that spontaneous mutations occur randomly with regard to their fitness effect. However, since the mutation rate varies along a genome and this variation can be subject to selection, organisms might evolve lower mutation rates at loci where mutations are most deleterious or increased rates where mutations are most needed. In fact, mechanisms of targeted hypermutation are known in organisms ranging from bacteria to humans. Here we review the main forces (...) driving the evolution of local mutation rates and identify the main limiting factors. Both targeted hyper‐ and hypomutation can evolve, although the former is restricted to loci under very frequent positive selection and the latter is severely limited by genetic drift. Nevertheless, we show how an association of repair with transcription or chromatin‐associated proteins could overcome the drift limit and lead to non‐random hypomutation along the genome in most organisms.Editor's suggested further reading in BioEssays Stress‐induced mutation via DNA breaks in Escherichia coli: A molecular mechanism with implications for evolution and medicine Abstract. (shrink)

Port-wine birthmarks (PWBs) are caused by somatic, mosaic mutations in the G protein guanine nucleotide binding protein alpha subunit q (GNAQ) and are characterized by the formation of dilated, dysfunctional blood vessels in the dermis, eyes, and/or brain. Cutaneous PWBs can be treated by current dermatologic therapy, like laser intervention, to lighten the lesions and diminish nodules that occur in the lesion. Involvement of the eyes and/or brain can result in serious complications and this variation is termed Sturge-Weber syndrome (SWS). (...) Some of the biggest hurdles preventing development of new therapeutics are unanswered questions regarding disease biology and lack of models for drug screening. In this review, we discuss the current understanding of GNAQ signaling, the standard of care for patients, overlap with other GNAQ-associated or phenotypically similar diseases, as well as deficiencies in current in vivo and in vitro vascular malformation models. (shrink)

A cell contains many copies of mitochondrial DNA. The distribution of a mitochondrial gene mutation in a cell culture is governed by the way in which the mtDNA molecules of a cell are replicated and partitioned between the two daughter cells during mitosis. Assuming that this partition process is random, we describe the evolution of the mitochondrial genetic state of a cell culture. The mutated mtDNA is ultimately segregated and the rate of the trend to segregation is relatively slow. (...) It is nevertheless greatly accelerated if the model takes into account the spatial mtDNA partition by the mitochondrial compartments. (shrink)

Biological modalities (e.g., biological possibility, necessity and counterfactuality) play an important explanatory role in biological practice. However, biological modalities lack truth conditions and the inferential relationship between biological and other modalities is unclear. This thesis addresses these problems, first, by improving upon Daniel Dennett's Library of Mendel. Second, a family of modal logics is introduced. In the simplest model, states are interpreted as codons, the binary relation is interpreted as single substitution mutation and the valuation induces a partition of (...) blocks of codons that code for some amino acid. In addition, the proposed framework allows for a grading of biological possibility and captures various competing notions of biological possibility. Applications include a model checker and a lawless Lewis-style semantics for biological counterfactuals. In short, this thesis lays the groundwork for a theory of biological modalities. (shrink)

De Vries' mutation theory has not stood the test of time. The supposed mutations of Oenothera were in reality complex recombination phenomena, ultimately explicable in Mendelian terms, while instances of large-scale mutations were found wanting in other species. By 1915 the mutation theory had begun to lose its grip on the biological community; by de Vries' death in 1935 it was almost completely abandoned. Yet, as we have seen, during the first decade of the present century it achieved (...) an enormous popularity. As this paper has tried to suggest, one of the principal reasons for this was that de Vries' theory served as a banner around which a whole crowd of disaffected Darwinians or anti-Darwinians could rally. However, not all of those who favored de Vries did so for quite the same reasons. Underlying the multitude of views ran several common threads: a dissatisfaction with current Darwinian theory born out of misunderstanding natural selection, a general misunderstanding of the nature of species, and a prejudice against speculative, nontestable theories in biology.Supporters of de Vries were not the only opponents of Darwinism, nor was the mutation theory the only alternative to natural selection. In the early twentieth century a number of theories had been proposed to explain away the problems which Darwin had left unsolved. There was the idea of orthogenesis, championed by the American paleontologists Cope, Osborn and others; organic selection (or orthoplasy) was championed by M. M. Baldwin and C. Lloyd Morgan; there were the concepts of convergent evolution proposed by Hermann Friedmann, the theory of physiological selection by John George Romanes, and the concepts of reproductive divergence by H. M. Vernon. Virtually none of these men either accepted or were strong supporters of the de Vriesian theory, for each had his own particular ‘ism” to advocate as the major factor in evolution. The existence of a large number of such theories, each purporting to be the explanation, was characteristic of evolutionary theory at the turn of the century. It is to a large extent the emphasis on such fragmentary concepts that retarded development of the comprehensive theory of evolution which emerged in the 1920's and 1930's. For the historian, however, a study of these alternative theories is instructive in trying to understand the inherent difficulties which Dawwinian theory posed to biologists at the time. De Vries' mutation theory serves historically as a mirror to reflect the critical mood of a generation hostile to the theory of natural selection.It has often been claimed that it was impossible to understand the mechanism of natural selection until it could be placed in genetic and mathematical terms. It is certainly true that great strides have been made in population genetics and the treatment of evolutionary concepts with mathematical tools in the last forty years. But the very people who developed the genetical and mathematical approach to evolution were already convinced of the essential correctness of Darwinian theory before they started. Advances in an understanding of Mendelian heredity aided greatly in solving one important issue for evolutionists: the origin of variations. And the rigor with which selection acted could best be studied by observing changes in gene frequencies (calculated mathematically) over a number of generations. But as this paper has shown, two of the basic problems which biologists faced in evaluating Darwinian theory at the turn of the century-the nature of species, and the criteria of what constituted an acceptable explanation in biological science-could not be answered directly by mathematics. What mathematical and genetical theory did do was to help convince the skeptics of the validity of the Darwinian proposition.The change in explanatory criteria which many hailed as de Vries' most important contribution to evolutionary theory seems to have been part of a general emergence of twentieth-century biology from the domination of theorizers in the nineteenth. It also marked the emergence of America from the domination of biological, and particularly evolutionary, influence of Europeans. The change occurred in three areas: in the kinds of questions asked: testable versus non-testable; in the kind of data sought: quantitative versus qualitative; and in the kinds of theories proposed: analytical and reductive—the attempt to see complex processes in terms of simpler components-as opposed to synthetic and speculative. Although ultimately wrong in his idea, de Vries and his theories rode high on the wave of “experimentalism” which was the harbinger of a new era in evolutionary theory. (shrink)

Since more than hundred years the attempts to explain biological adaptations constitute the main current of evolutionary thinking. In 1901 C. LI. Morgan wrote: „The doctrine of evolution has rendered the study of adaptation of scientific importance. Before that doctrine was formulated, natural adaptations formed part of the mystery of special creation, and played a great role in natural theology through the use of the argument from 'design in nature’". The modem doctrine of biology stresses the importance of the (...) environment in „shaping" the inner properties of every living being. This means an obvious although tacit refusal to assume or recognize any single, integrated agent in the origin of main functional biological traits and in the genesis of new kinds of life. The role ascribed to random mutations, and to „pressures of the environment" is just one aspect of the neodarwinian theory. Another aspect of this doctrine is the widespread conviction that all phenomena of life are a natural, both random and necessary result of interactions between constantly changing material objects. (shrink)

A biological explanation for the dependence of genome-wide mutation-rate variation on local base context is now becoming clearer. The proportions of G + C relative to A + T—expressed as GC%—is a species-specific DNA character. The frequencies of these single bases correlate with frequencies of corresponding oligonucleotides that are more-sensitive indicators of species specificity. Thus, when k = 3 there are 64 possible trinucleotide sequences and a GC%-rich species has a high frequency of GC-rich 3-mers. Closely related species have (...) similar k-mer patterns. For distantly related species, even if happening to have the same GC% values, k-mer patterns are widely discordant. Conventionally, a base substitution mutation is viewed as a chemical 1-mer phenomenon. However, the selective difference by which the corresponding mutation is scored usually relates to context. Thus, an A to U codon mutation in sickle cell anemia, rather than attracting an anticodon in a structural loop of glutamate tRNA, pairs with the more complementary anticodon loop of valine tRNA. Likewise, a recent statistical analysis of genome-wide mutation-rate variation supports the view that a failure of discordant DNA loops to pair at meiosis can initiate and/or sustain the speciation process. Such disharmony among base patterns may have unknowingly been hinted at by geneticist William Bateson who invoked a music metaphor when considering speciation mechanisms. (shrink)

Evolutionary gradualism, the randomness of mutations, and the hypothesis that natural selection exerts a pervasive and substantial influence on evolutionary outcomes are pair-wise logically independent. Can the claims about selection and mutation be used to formulate an argument for gradualism? In his Genetical Theory of Natural Selection, R.A. Fisher made an important start at this project in his famous “geometric argument” by showing that a random mutation that has a smaller effect on two or more phenotypes will have (...) a higher average fitness than a random mutation that has a larger phenotypic effect. Motoo Kimura’s demonstration that a gene’s probability of fixation depends on both the selection coefficient and the effective population size shows that Fisher’s argument for gradualism was mistaken. Here we analyze Fisher’s argument and explain how Kimura’s theory leads to a conclusion that Fisher did not anticipate. We identify a fallacy that reasoning about fitness differences and their evolutionary consequences should avoid. We then distinguish forward-directed from backward-directed versions of gradualism. The backward-directed thesis about a single mutation may be correct, but the forward-directed thesis is not. After that we consider a sequence of random mutations that all affect the same cluster of phenotypes and Allen Orr’s idea that there is an optimal sequence of mutation sizes, moving from larger to smaller as the population approaches a fixed optimum. This provides a likelihood justification for a forward-directed version of gradualism when there is a fixed optimum, but it also provides an argument against forward-directed gradualism if the optimum shifts substantially as the population evolves. Finally, we consider whether genome-wide association studies (GWASs) can furnish empirical evidence that bears on the truth of gradualism. The version of gradualism that GWASs directly bear on concerns the phenotypic effect size of a gene after it arises by mutation and has reached an appreciable frequency, not the phenotypic size of the mutation event itself. (shrink)

The proliferation of mitochondrial DNA (mtDNA) with deletion mutations has been linked to aging and age related neurodegenerative conditions. In this study we model the effect of mtDNA half-life on mtDNA competition and selection. It has been proposed that mutation deletions (mtDNAdel\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {mtDNA}_{del}$$\end{document}) have a replicative advantage over wild-type (mtDNAwild\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {mtDNA}_{wild}$$\end{document}) and that this is detrimental to the host cell, especially in (...) post-mitotic cells. An individual cell can be viewed as forming a closed ecosystem containing a large population of independently replicating mtDNA. Within this enclosed environment a selfishly replicating mtDNAdel\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {mtDNA}_{del}$$\end{document} would compete with the mtDNAwild\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {mtDNA}_{wild}$$\end{document} for space and resources to the detriment of the host cell. In this paper, we use a computer simulation to model cell survival in an environment where mtDNAwild\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {mtDNA}_{wild}$$\end{document} compete with mtDNAdel\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {mtDNA}_{del}$$\end{document} such that the cell expires upon mtDNAwild\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {mtDNA}_{wild}$$\end{document} extinction. We focus on the survival time for long lived post-mitotic cells, such as neurons. We confirm previous observations that mtDNAdel\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {mtDNA}_{del}$$\end{document} do have a replicative advantage over mtDNAwild\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {mtDNA}_{wild}$$\end{document}. As expected, cell survival times diminished with increased mutation probabilities, however, the relationship between survival time and mutation rate was non-linear, that is, a ten-fold increase in mutation probability only halved the survival time. The results of our model also showed that a modest increase in half-life had a profound affect on extending cell survival time, thereby, mitigating the replicative advantage of mtDNAdel\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text {mtDNA}_{del}$$\end{document}. Given the relevance of mitochondrial dysfunction to various neurodegenerative conditions, we propose that therapies to increase mtDNA half-life could significantly delay their onset. (shrink)

Ageing is a complex phenomenon which remains a major challenge to modern biology. Although the evolutionary biology of ageing is well understood, the mechanisms that limit lifespan are unknown. The isolation and analysis of single‐gene mutations which extend lifespan (Age mutations) is likely to reveal processes which influence ageing. Caenorhabditis elegans is the only metazoan in which Age mutations have been identified. The Age mutations not only prolong life, but also confer a complex array of other phenotypes. Some (...) of these phenotypes provide clues to the evolutionary origins of these genes while others allude to mechanisms of lifespan‐extension. Many of the Age genes interact and share a second common phenotype, that of stress resistance. Rather than invertebrate ageing being determined by a ‘clock mechanism’, a picture is emerging of ageing as a non‐adaptive process determined, in part, by resistance to intrinsic stress mediated by stress‐response genes. (shrink)

Pleiotropy, in which one mutation causes multiple phenotypes, has traditionally been seen as a deviation from the conventional observation in which one gene affects one phenotype. Epistasis, or gene–gene interaction, has also been treated as an exception to the Mendelian one gene–one phenotype paradigm. This simplified perspective belies the pervasive complexity of biology and hinders progress toward a deeper understanding of biological systems. We assert that epistasis and pleiotropy are not isolated occurrences, but ubiquitous and inherent properties of (...) biomolecular networks. These phenomena should not be treated as exceptions, but rather as fundamental components of genetic analyses. A systems level understanding of epistasis and pleiotropy is, therefore, critical to furthering our understanding of human genetics and its contribution to common human disease. Finally, graph theory offers an intuitive and powerful set of tools with which to study the network bases of these important genetic phenomena. (shrink)

Theorists have oversold the usefulness of predicate logic and generative grammar to the study of language origins. They have searched for models that correspond to semantic properties, such as truth, when what is needed is an empirically testable model of evolution. Such a model is required if we are to explain the origins of linguistic properties by appealing to general properties of linguistic engendering, rather than to the advent of genotypes with the propensity to produce certain brain mechanisms. While the (...) latter sort of explanation has a place, no theory can be considered an ‘evolutionary’ theory without the former. We introduce a general notion of engendering, whose primary virtue is its freedom from assumptions regarding the nature of colloquial change. We use it to frame a conjecture about the evolution of centre embedded clauses; one which makes the fewest possible assumptions about the neural requirements upon individual brains. Keywords: biology of language; epigenesis; engendering; evolution; mutation; population; recursion. (shrink)

In the case of synthetic biology, the responsibility of humanity for the creation of new technologies that interfere with the processes of natural selection and evolution of species can be invoked, thus annihilating the complex ecological balances and possibly leading to uncontrollable genetic mutations. The big ethical questions are raised by the fact that viral genetic material is hybridized with synthetic genetic material, as well as with the genetic material that underlies the DNA of various living cells, that might (...) interfere with synthetic genetic material - either due to errors in the handling of genetic content or the inability to predict the evolution of synthetic biological systems, an evolution beyond any mathematical modeling that would allow the estimation of biological risks given by the appearance of new species - partially or totally synthetic - and especially by their spread in ecosystems. In this article we will plead for an ethical modeling of technology and a wider communication between ethicist and bio-engineers in order to estimate the directions of technological evolution, especially in the case of synthetic biology. (shrink)

In 1935 geneticist Nikolai Timoféeff-Ressovsky, radiation physicist Karl G. Zimmer, and quantum physicist Max Delbrück published “On the Nature of Gene Mutation and Gene Structure,” known subsequently as the “Three-Man Paper.” This seminal paper advanced work on the physical exploration of the structure of the gene through radiation physics and suggested ways in which physics could reveal definite information about gene structure, mutation, and action. Representing a new level of collaboration between physics and biology, it played an (...) important role in the birth of the new field of molecular biology. The paper’s results were popularized for a wide audience in the What is Life? lectures of physicist Erwin Schrödinger in 1944. Despite its historical impact on the biological sciences, the paper has remained largely inaccessible because it was only published in a short-lived German periodical. Creating a Physical Biology makes the Three Man Paper available in English for the first time. Brandon Fogel’s translation is accompanied by an introductory essay by Fogel and Phillip Sloan and a set of essays by leading historians and philosophers of biology that explore the context, contents, and subsequent influence of the paper, as well as its importance for the wider philosophical analysis of biological reductionism. (shrink)

Fanconi anaemia (FA) comprises a group of autosomal recessive disorders resulting from mutations in one of eight genes (FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF and FANCG). Although caused by relatively simple mutations, the disease shows a complex phenotype, with a variety of features including developmental abnormalities and ultimately severe anaemia and/or leukemia leading to death in the mid teens. Since 1992 all but two of the genes have been identified, and molecular analysis of their products has revealed a complex (...) mode of action. Many of the proteins form a nuclear multisubunit complex that appears to be involved in the repair of double‐strand DNA breaks. Additionally, at least one of the proteins, FANCC, influences apoptotic pathways in response to oxidative damage. Further analysis of the FANC proteins will provide vital information on normal cell responses to damage and allow therapeutic strategies to be developed that will hopefully supplant bone marrow transplantation. BioEssays 24:439–448, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

The gain of a selective advantage in cancer as well as the establishment of complex traits during evolution require multiple genetic alterations, but how these mutations accumulate over time is currently unclear. There is increasing evidence that a mutator phenotype perpetuates the development of many human cancers. While in some cases the increased mutation rate is the result of a genetic disruption of DNA repair and replication or environmental exposures, other evidence suggests that endogenous DNA damage induced by AID/APOBEC (...) cytidine deaminases can result in transient localized hypermutation generating simultaneous, closely spaced (i.e. “clustered”) multiple mutations. Here, we discuss mechanisms that lead to mutation cluster formation, the biological consequences of their formation in cancer and evidence suggesting that APOBEC mutagenesis can also occur genome‐wide. This raises the possibility that dysregulation of these enzymes may enable rapid malignant transformation by increasing mutation rates without the loss of fitness associated with permanent mutators. (shrink)

Since more than hundred years the attempts to explain biological adaptations constitute the main current of evolutionary thinking. In 1901 C. LI. Morgan wrote: „The doctrine of evolution has rendered the study of adaptation of scientific importance. Before that doctrine was formulated, natural adaptations formed part of the mystery of special creation, and played a great role in natural theology through the use of the argument from 'design in nature’". The modem doctrine of biology stresses the importance of the (...) environment in „shaping" the inner properties of every living being. This means an obvious although tacit refusal to assume or recognize any single, integrated agent in the origin of main functional biological traits and in the genesis of new kinds of life. The role ascribed to random mutations, and to „pressures of the environment" is just one aspect of the neodarwinian theory. Another aspect of this doctrine is the widespread conviction that all phenomena of life are a natural, both random and necessary result of interactions between constantly changing material objects. (shrink)

The use of a reporter gene in transgenic mice indicates that there are many local mutations and large genomic rearrangements per somatic cell that accumulate with age at different rates per organ and without visible effects. Dissociation of the cells for monolayer culture brings out great heterogeneity of size and loss of function among cells that presumably reflect genetic and epigenetic differences among the cells, but are masked in organized tissue. The regulatory power of a mass of contiguous normal cells (...) is expressed in its capacity to normalize the appearance and growth behavior of solitary homophilic neoplastic cells, and to redirect differentiation of solitary heterophilic stem‐like cells. Intimate contact between the interacting cells is required to induce these changes. The normalization of the neoplastic phenotype does not require gap junctional communication between cells, though transdifferentiation might. These varied relationships are manifestations of the unifying biological principle of “order in the large over heterogeneity in the small”. BioEssays 28: 515–524, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Thomas Kuhn described the progress of science as comprising occasional paradigm shifts separated by interludes of ‘normal science’. The paradigm that has held sway since the inception of molecular biology is that genes (mainly) encode proteins. In parallel, theoreticians posited that mutation is random, inferred that most of the genome in complex organisms is non‐functional, and asserted that somatic information is not communicated to the germline. However, many anomalies appeared, particularly in plants and animals: the strange genetic phenomena (...) of paramutation and transvection; introns; repetitive sequences; a complex epigenome; lack of scaling of (protein‐coding) genes and increase in ‘noncoding’ sequences with developmental complexity; genetic loci termed ‘enhancers’ that control spatiotemporal gene expression patterns during development; and a plethora of ‘intergenic’, overlapping, antisense and intronic transcripts. These observations suggest that the original conception of genetic information was deficient and that most genes in complex organisms specify regulatory RNAs, some of which convey intergenerational information. Also see the video abstract here: https://youtu.be/qxeGwahBANw. (shrink)

Theorists have oversold the usefulness of predicate logic and generative grammar to the study of language origins. They have searched for models that correspond to semantic properties, such as truth, when what is needed is an empirically testable model of evolution. Such a model is required if we are to explain the origins of linguistic properties by appealing to general properties of linguistic engendering, rather than to the advent of genotypes with the propensity to produce certain brain mechanisms. While the (...) latter sort of explanation has a place, no theory can be considered an `evolutionary' theory without the former. We introduce a general notion of engendering, whose primary virtue is its freedom from assumptions regarding the nature of colloquial change. We use it to frame a conjecture about the evolution of centre embedded clauses; one which makes the fewest possible assumptions about the neural requirements upon individual brains. Keywords: biology of language; epigenesis; engendering; evolution; mutation; population; recursion. (shrink)

Erect posture and large brain are two of the most significant anatomical traits that distinguish us from nonhuman primates. But humans are also different from chimpanzees and other animals, and no less importantly, in their behavior, both as individuals and socially. Distinctive human behavioral attributes include tool-making and technology; abstract thinking, categorizing, and reasoning; symbolic (creative) language; self-awareness and death-awareness; science, literature, and art; legal codes, ethics and religion; complex social organization and political institutions. These traits may all be said (...) to be components of human culture, a distinctively human mode of adaptation to the environment that is far more versatile and successful than the biological mode. Cultural adaptation is more effective than biological adaptation because its innovations are directed, rather than random mutations; because it can be transmitted "horizontally", rather than only "vertically", to descendants; and because cultural heredity is Lamarckian, rather than Mendelian, so that acquired characteristics can be inherited. I explore ethics as a distinctive human trait. The question whether ethical behavior is biologically determined may refer either to the capacity for ethics (i.e., the proclivity to judge human actions as either right or wrong), or to the moral norms accepted by human beings for guiding their actions. I will propose: (1) that the capacity for ethics is a necessary attribute of human nature; and (2) that moral norms are products of cultural evolution, not of biological evolution. (shrink)

While Darwin pictured organismal evolution as “descent with modification” more than 150 years ago, a detailed reconstruction of the basic evolutionary transitions at the molecular level is only emerging now. In particular, the evolution of today's protein structures and their concurrent functions has remained largely mysterious, as the destruction of these structures by mutation seems far easier than their construction. While the accumulation of genomic and structural data has indicated that proteins are related via common ancestors, naturally occurring protein (...) structures are often considered to be evolutionarily robust, thus leaving open the question of how protein structures can be remodelled while selective pressure forces them to function. New information on the proteome, however, increasingly explains the nature of local and global conformational diversity in protein evolution, which allows the acquisition of novel functions via molecular transition forms containing ancestral and novel structures in dynamic equilibrium. Such structural plasticity may permit the evolution of new protein folds and help account for both the origins of new biological functions and the nature of molecular defects. BioEssays 29:1095–1104, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Mutations that disrupt biological rhythms have existed in microbial and metazoan eukaryotes for some time. They have recently begun to be studied with increasing intensity, both in terms of phenotypic effects of the relevant genetic variants, and with regard to molecular isolation and analysis of the genes defined by two of the ‘clock mutations’. These genetic loci, called period (per) in Drosophila and frequency (frq) in Neurospora, influence not only the basic characteristics of circadian rhythmicity, but also temperature compensation of (...) such daily cycle durations, ‘re‐setting’ of the rhythms' phases, and (for the per mutants) behavioral oscillations associated with much shorter than circadian periodicities. Molecular cloning of Drosophila's per gene, accompanied crucially by the locus's identification in germ‐line transformants, has led to information on its expression ‐ temporally, spatially, and in regard to heterogeneity of mRNA types. Nucleotide‐sequencing analyses of genomic DNA (and/or cDNA) from normal and mutated per alleles have (1) led to the suggestion that this clock gene encodes a family of proteoglycans (which was further indicated by application of antibody reagents obtained by manipulation of one of the gene's exons); and (2) shown that the three types of per mutations ‐ which shorten or lengthen rhythm periodicities or appear to eliminate them ‐ are associated with interesting amino‐acid substitutions or a stop codon, respectively. Analogous molecular findings are awaited from Neurospora, whose frq gene has very recently been cloned and definitively identified, in part via transformation experiments. (shrink)

Evolutionary epistemology has experienced a continuous rise over the last decades. Important new theoretical considerations and novel empirical findings have been integrated into the existing framework. In this paper, I would like to suggest three lines of research that I believe will significantly contribute to further advance EE: ontogenetic considerations, key ideas from cognitive biology, and the framework of the Extended Evolutionary Synthesis. EE, in particular the program of the evolution of epistemological mechanisms, seeks to provide a phylogenetic account (...) of the generation of cognitive processes underlying knowledge creation. Traditionally, EE and EEM have been oriented towards an account of evolutionary theory that mainly drew from the tenets of the Modern Synthesis. The Modern Synthesis largely dismisses ontogenetic processes and considers them irrelevant for evolutionary explanations. If anything, the role of development in evolution is believed to be that of a constraint. There is, however, ample evidence for a tight intertwinement of developmental and evolutionary processes. Organisms employ their cognitive apparatus to interact with the environment in order to achieve a fully functioning perceptual and cognitive nervous system. Also, ontogeny provides generative potentials to enable variations that natural selection can act upon. EEM’s agenda may, therefore, strongly benefit from bringing together ontogenetic and phylogenetic approaches. To grapple with this challenge, an alternative vision of the evolutionary theory termed Extended Evolutionary Synthesis could be used. This extended evolutionary theory explores relationships between the processes of individual development and phenotypic change during evolution and can provide a more suitable framework for EEM to draw from. In recent years, cognitive biology has gained momentum as an independent research field. Cognitive biology builds on the concepts of EEM and understands knowledge as a biogenic phenomenon. Its main objective is also the formulation of substantiated interrelations between cognition and evolution but it focuses on cognitive functionality at all levels of biological organization. It thus employs a “vertical” approach that encompasses nested hierarchies which span from single molecules, cells, and tissues to the organismal level, communities, and societies. In contrast to cognitive biology, EEM is here understood to adopt a “horizontal” approach that focuses on phylogenetic explanations of cognition and knowledge acquisition. Linking EEM with the key ideas of cognitive biology could make EEM’s research program stronger as it can more easily accommodate phylogenetic and ontogenetic questions within a hierarchical, multilevel perspective. This is of particular importance for a more comprehensive account of cognition since living systems are subject to context-dependent causal influences from different organizational levels. In addition to EEM, there is a second program of EE. This program has been labeled evolutionary epistemology of theories and understands the increase in human knowledge, such as scientific theories, as naturalistic accounts of evolution. Both, EEM and EET initially drew from the core concepts of the Modern Synthesis. Several scholars have severely criticized the analogies made between EET and the Neo-Darwinian key processes of evolution. In particular processes of random mutation, the rate of variation, natural selection as the unique driving force, and the adaptationist agenda are believed to reveal disanalogies. In contrast to the Modern Synthesis, the Extended Evolutionary Synthesis not only recognizes developmental processes but also ecological interactions and systems dynamics as well as social and cultural evolutionary reciprocity as important evolutionary processes. Concepts of the Extended Evolutionary Synthesis are therefore expected to be more fruitful for re-conceptualizing parallels between scientific theorizing and biological evolution. (shrink)

Here we discuss the challenge posed by self-organization to the Darwinian conception of evolution. As we point out, natural selection can only be the major creative agency in evolution if all or most of the adaptive complexity manifest in living organisms is built up over many generations by the cumulative selection of naturally occurring small, random mutations or variants, i.e., additive, incremental steps over an extended period of time. Biological self-organization—witnessed classically in the folding of a protein, or in the (...) formation of the cell membrane—is a fundamentally different means of generating complexity. We agree that self-organizing systems may be fine-tuned by selection and that self-organization may be therefore considered a complementary mechanism to natural selection as a causal agency in the evolution of life. But we argue that if self-organization proves to be a common mechanism for the generation of adaptive order from the molecular to the organismic level, then this will greatly undermine the Darwinian claim that natural selection is the major creative agency in evolution. We also point out that although complex self-organizing systems are easy to create in the electronic realm of cellular automata, to date translating in silico simulations into real material structures that self-organize into complex forms from local interactions between their constituents has not proved easy. This suggests that self-organizing systems analogous to those utilized by biological systems are at least rare and may indeed represent, as pre-Darwinists believed, a unique ascending hierarchy of natural forms. Such a unique adaptive hierarchy would pose another major challenge to the current Darwinian view of evolution, as it would mean the basic forms of life are necessary features of the order of nature and that the major pathways of evolution are determined by physical law, or more specifically by the self-organizing properties of biomatter, rather than natural selection. (shrink)

There is an argument that has recently been deployed in favor of thinking that the mind is mostly (or even exclusively) composed of cognitive modules; an argument that draws from some ideas and concepts of evolutionary and of developmental biology. In a nutshell, the argument concludes that a mind that is massively composed of cognitive mechanisms that are cognitively modular (henceforth, c-modular) is more evolvable than a mind that is not c-modular (or that is scarcely c-modular), since a cognitive (...) mechanism that is c-modular is likely to be biologically modular (henceforth, b-modular), and b-modular characters are more evolvable (e.g., Sperber 2002, Carruthers 2005). In evolutionary biology, the evolvability of a character in an organism is understood as the “organism’s capacity to facilitate the generation of non-lethal selectable phenotypic variation from random mutation” with respect to that character. Here I will argue that the notion of cognitive modularity needed to make this argument plausible will have to be understood in terms of the biological notion of variational independence; that is, it will have to be understood in such a way that a cognitive feature is c-modular only if few or no other morphological changes (cognitive and not) are significantly correlated with variations of that feature arising in members of the relevant population. I will also argue that all –except for (possibly) one—of the connotations contained in a cluster of notions of cognitive modularity widely accepted in some of the mainstream currents of thought in classical cognitive science, are simply irrelevant to the argument. In order to argue for this, I will have to examine the question as to whether there are any strong theoretical connections between (1) those connotations and (2) notions of modularity accepted in biology, specially in evolutionary and in developmental biology, that are thought to be most relevant to arguments to the effect that biological modularity enhances evolvability. (shrink)

In "The Indeterministic Character of Evolutionary Theory: No 'Hidden Variables Proof' But No Room for Determinism Either," Brandon and Carson (1996) argue that evolutionary theory is statistical because the processes it describes are fundamentally statistical. In "Is Indeterminism the Source of the Statistical Character of Evolutionary Theory?" Graves, Horan, and Rosenberg (1999) argue in reply that the processes of evolutionary biology are fundamentally deterministic and that the statistical character of evolutionary theory is explained by epistemological rather than ontological considerations. (...) In this paper I focus on the topic of mutation. By focusing on some of the theory and research on this topic from early to late, I show how quantum indeterminism hooks up to point mutations (via tautomeric shifts, proton tunneling, and aqueous thermal motion). I conclude with a few thoughts on some of the wider implications of this topic. (shrink)

Nelson and Winter’s An Evolutionary Theory of Economic Change (1982) was the foundational work of what has become the thriving sub-discipline of evolutionary economics. In attempting to develop an alternative to neoclassical economics, the authors looked to borrow basic ideas from biology, in particular a concept of economic “natural selection.” However, the evolutionary models they construct in their seminal work are in many respects quite different from the models of evolutionary biology. There is no reproduction in any usual (...) sense, “mutation” is directed as opposed to blind, and there is no meaningful distinction between phenotype and genotype. Despite these substantial departures from the conceptions of evolutionary biology, I argue that the “evolutionary” economics of Nelson and Winter is indeed a legitimate extension of Darwinian evolutionary principles to a novel domain, and that the traditional conception of evolution by natural selection must be revised. The novel features of evolutionary economics models reflect the distinctive theoretical requirements faced by economists. I further contend that reproduction, heredity, blind variation, and the genotype/phenotype distinction are all inessential to evolutionary theory, and that their role in evolutionary biology is a domain-specific feature of biological theory. (shrink)

Evolutionary systems biology (ESB) is a rapidly growing integrative approach that has the core aim of generating mechanistic and evolutionary understanding of genotype‐phenotype relationships at multiple levels. ESB's more specific objectives include extending knowledge gained from model organisms to non‐model organisms, predicting the effects of mutations, and defining the core network structures and dynamics that have evolved to cause particular intracellular and intercellular responses. By combining mathematical, molecular, and cellular approaches to evolution, ESB adds new insights and methods to (...) the modern evolutionary synthesis, and offers ways in which to enhance its explanatory and predictive capacities. This combination of prediction and explanation marks ESB out as a research manifesto that goes further than its two contributing fields. Here, we summarize ESB via an analysis of characteristic research examples and exploratory questions, while also making a case for why these integrative efforts are worth pursuing. (shrink)

A superposition of the field ofmeaning or set of concepts proper to process philosophy and theology upon the field ofmeaning proper to contemporary biology (in what Mary Gerhart and Allan Russell call “metaphoric process”) yields some interesting results for both disciplines. Gene mutations within cells can be philosophically explained as a society of actual entities deviating from the normal pattern ofdevelopment within the structured society proper to a cell and the different genes at work in it. The notion of (...) supervenience or emergence within biology confirms that developing organisms exercise a form of causation upon their ultimate constituents (actual entities) that is more than and quite different from what these constituents produce on their own through bottom-up causation from moment to moment. (shrink)

This paper addresses the question, which sex ratio will evolve in a population that is subject to mutation and drift. The problem is analyzed using a simulation model as well as analytical methods. A detailed simulation model for the evolution of a population's allele distribution shows that for the sex ratio game a wide spectrum of different population states may evolve from on the one hand a monomorphic state with one predominant allele and with all other alleles suppressed by (...) the forces of selection, to on the other hand a polymorphism determined by recurrent mutations. Which of these states will evolve depends on the population size, the mating system and the rate of mutations. For the sex ratio game the evolutionarily stable strategy (ESS), as defined by evolutionary game theory, can only predict the population sex ratio but not the underlying stable population state. A comparison of different approaches to the problem shows that false predictions of the stable population states might result from two simplifying assumptions that are fairly common in evolutionary biology:a) it is assumed that mutations are rare events and there is never more than one mutant gene present in a population at any one time; b) a deterministic relationship is assumed between the fitness assigned to an individual's strategy and the individual's contribution to the gene pool of future generations. (shrink)

The primary impediment to formulating a general theory for adaptive evolution has been the unknown distribution of fitness effects for new beneficial mutations. By applying extreme value theory, Gillespie circumvented this issue in his mutational landscape model for the adaptation of DNA sequences, and Orr recently extended Gillespie's model, generating testable predictions regarding the course of adaptive evolution. Here we provide the first empirical examination of this model, using a single-stranded DNA bacteriophage related to phiX174, and find that our data (...) are consistent with Orr's predictions, provided that the model is adjusted to incorporate mutation bias. Orr's work suggests that there may be generalities in adaptive molecular evolution that transcend the biological details of a system, but we show that for the model to be useful as a predictive or inferential tool, some adjustments for the biology of the system will be necessary. (shrink)

Although quantum mechanics can accurately predict the probability distribution of outcomes in an ensemble of identical systems, it cannot predict the result of an individual system. All the local and global hidden variable theories attempting to explain individual behavior have been proved invalid by experiments (violation of Bell’s inequality) and theory. As an alternative, Schrodinger and others have hypothesized existence of free will in every particle which causes randomness in individual results. However, these free will theories have failed to quantitatively (...) explain the quantum mechanical results. In this paper, we take the clue from quantum biology to get the explanation of quantum mechanical distribution. Recently it was reported that mutations (which are quantum processes) in DNA of E. coli bacteria instead of being random were biased in a direction such that the chance of survival of the bacteria is increased. Extrapolating it, we assume that all the particles including inanimate fundamental particles have a will and that is biased to satisfy the collective goals of the ensemble. Using this postulate, we mathematically derive the correct spin probability distribution without using quantum mechanical formalism (operators and Born’s rule) and exactly reproduce the quantum mechanical spin correlation in entangled pairs. Using our concept, we also mathematically derive the form of quantum mechanical wave function of free particle which is conventionally a postulate of quantum mechanics. Thus, we prove that the origin of quantum mechanical results lies in the will (or consciousness) of the objects biased by the collective goal of ensemble or universe. This biasing by the group on individuals can be called as “coherence” which directly represents the extent of life present in the ensemble. So, we can say that life originates out of establishment of coherence in a group of inanimate particles. (shrink)

Walter M. Miller, Jr.’s 1959 novel A Canticle for Leibowitz is on one level a theological reflection on the human propensity to sin. Not coincidentally, the story is located in an Albertinian abbey in the former American southwest six hundred years after a nuclear holocaust, recounting three separate historical periods over the following twelve hundred years: a dark age, a scientific renaissance, and finally a time of technological achievement where a second nuclear holocaust is imminent. Miller asks the question of (...) whether humans as a species cannot avoid committing acts of sin that cumulatively and continually lead to acts of societal and technological self-destruction; his response oscillates between a fatalistic pessimism (the final extinction of the human species) and a vague optimism (the “new creature,” the mutant Rachel, or perhaps a last group of humans leaving the Earth as the curtain falls). It is my thesis in this article that theological questions about sin (as explored by Augustine and later scholars) can be fruitfully approached by analogous genetic processes; more precisely by reference to the rising science of Epigenetics, which explores how genes can express themselves differently without mutating in response to life stressors. In light of the idea of a genetic and epigenetic expression of moral rules of existence, Augustine’s thesis of original sin as something that is inherited makes new sense. In this light, it may also be possible to approach the question that the Canticle proposes: are we destined to self-destruction, or is there a way out of this destructive cycle? (shrink)

In this paper we explore the rise of ‘the breast cancer gene’ as a field of medical, cultural and personal knowledge. We address its significance in the Norwegian public health care system in relation to so-called biological citizenship in this particular national context. One of our main findings is that, despite its claims as a measure for health and disease prevention, gaining access to medical knowledge of BRCA 1/2 breast cancer gene mutations can also produce severe instability in the individuals (...) and families affected. That is, although gene testing provides modern subjects with an opportunity to foresee their biological destiny and thereby become patients in waiting, it undoubtedly also comes with difficult existential dilemmas and choices, with implications that resonate beyond the individual and into different family and love relations. By elaborating on this finding we address the question of whether the empowerment slogan, which continues to be advocated through various health, BRCA and breast cancer discourses, reinforces a naïve or an idealized notion of the actively responsible patient: resourceful enough to seek out medical expertise and gain sufficient knowledge, on which to base informed decisions, thereby reducing the future risk of developing disease. In contrast to this ideal, our Norwegian informants tell a different story, in which there is no apparent heroic mastery of genetic fates, but rather a pragmatic attitude to dealing with a dire situation over which they have little control, despite having complied with medical advice through national guidelines and follow-up procedures for BRCA 1/2 carriers. In conclusion we claim that the sense of safety that gene testing and its associated medical solutions allegedly promise to provide proved illusory. Although BRCA-testing offers the potential for protection from adverse DNA-heritage, administered through possibilities for self-monitoring and self-management of the body, the feeling of ‘being in good health’ has hardly been reinforced by the emergence of gene technology. (shrink)

The “DNA is a program” metaphor is still widely used in Molecular Biology and its popularization. There are good historical reasons for the use of such a metaphor or theoretical model. Yet we argue that both the metaphor and the model are essentially inadequate also from the point of view of Physics and Computer Science. Relevant work has already been done, in Biology, criticizing the programming paradigm. We will refer to empirical evidence and theoretical writings in Biology, (...) although our arguments will be mostly based on a comparison with the use of differential methods (in Molecular Biology: a mutation or alike is observed or induced and its phenotypic consequences are observed) as applied in Computer Science and in Physics, where this fundamental tool for empirical investigation originated and acquired a well-justified status. In particular, as we will argue, the programming paradigm is not theoretically sound as a causal(as in Physics) or deductive(as in Programming) framework for relating the genome to the phenotype, in contrast to the physicalist and computational grounds that this paradigm claims to propose. (shrink)

Non‐Interventionist Objective Divine Action (NIODA), introduced by Robert John Russell, is a model of divine action drawing upon insights from quantum mechanics. It presents an intriguing and significant challenge to classical conceptions of divine action with far‐reaching consequences. When applying NIODA to theistic evolution, however, significant questions emerge that require attention. We identify and assess two sets of concerns. The first relates to quantum physics, particularly whether and how quantum occurrences influence mutations and evolution. We argue that the current empirical (...) evidence is ambiguous in its support of the kinds of quantum action that Russell proposes, though emerging data from quantum biology look promising. The second set of concerns is metaphysical, especially concerning the problem of evil. NIODA gives Godextensive agency over evolution and genetics, which has adverse consequences for theodicy. We propose potential solutions to the problems highlighted in our article, both metaphysical and physical, to improve the viability of NIODA's application to theistic evolution. (shrink)

With a previous paper (Niu & Wang, 1995), a general, hypothetical outline of the mechanism of carcinogenesis was proposed. With reference to the fact of starvation-induced hypermutation in micro-organisms, we propose that the hypoxia commonly seen in the cells at the centre of solid tumours might also result in hypermutation, and then p53-dependent programmed cell death. Like the apparently adaptive mutations in micro-organisms, only those genes (e.g. p53) that enable the cells to escape from apoptosis may be selected.

The combination of evolutionary with engineering principles will enhance synthetic biology. Conversely, synthetic biology has the potential to enrich evolutionary biology by explaining why some adaptive space is empty, on Earth or elsewhere. Synthetic biology, the design and construction of artificial biological systems, substitutes bio‐engineering for evolution, which is seen as an obstacle. But because evolution has produced the complexity and diversity of life, it provides a proven toolkit of genetic materials and principles available to synthetic (...) biology. Evolution operates on the population level, with the populations composed of unique individuals that are historical entities. The source of genetic novelty includes mutation, gene regulation, sex, symbiosis, and interspecies gene transfer. At a phenotypic level, variation derives from regulatory control, replication and diversification of components, compartmentalization, sexual selection and speciation, among others. Variation is limited by physical constraints such as diffusion, and chemical constraints such as reaction rates and membrane fluidity. While some of these tools of evolution are currently in use in synthetic biology, all ought to be examined for utility. A hybrid approach of synthetic biology coupled with fine‐tuning through evolution is suggested. (shrink)