Why the DNA‐containing organelles, chloroplasts, and mitochondria, are inherited maternally is a long standing and unsolved question. However, recent years have seen a paradigm shift, in that the absoluteness of uniparental inheritance is increasingly questioned. Here, we review the field and propose a unifying model for organelle inheritance. We argue that the predominance of the maternal mode is a result of higher mutational load in the paternal gamete. Uniparental inheritance evolved from relaxed organelle inheritance patterns because it avoids the spread (...) of selfish cytoplasmic elements. However, on evolutionary timescales, uniparentally inherited organelles are susceptible to mutational meltdown (Muller's ratchet). To prevent this, fall‐back to relaxed inheritance patterns occurs, allowing low levels of sexual organelle recombination. Since sexual organelle recombination is insufficient to mitigate the effects of selfish cytoplasmic elements, various mechanisms for uniparental inheritance then evolve again independently. Organelle inheritance must therefore be seen as an evolutionary unstable trait, with a strong general bias to the uniparental, maternal, mode. (shrink)

Plastids and mitochondria arose through endosymbiotic acquisition of formerly free-living bacteria. During more than a billion years of subsequent concerted evolution, the three genomes of plant cells have undergone dramatic structural changes to optimize the expression of the compartmentalized genetic material and to fine-tune the communication between the nucleus and the organelles. The chimeric composition of many multiprotein complexes in plastids and mitochondria (one part of the subunits being nuclear encoded and another one being encoded in the organellar genome) (...) provides a paradigm for co-evolution at the cellular level. In this paper, we discuss the co-evolution of nuclear and organellar genomes in the context of environmental adaptation in species and populations. We highlight emerging genetic model systems and new experimental approaches that are particularly suitable to elucidate the molecular basis of co-adaptation processes and describe how nuclear-cytoplasmic co-evolution can cause genetic incompatibilities that contribute to the establishment of hybridization barriers, ultimately leading to the formation of new species. (shrink)

Human germline genome editing is increasingly being seen as acceptable provided certain conditions are satisfied. Accordingly, genetic modifications would take place on eggs or sperm (or their prec...

The genomics “revolution” is spreading. Originating in the molecular life sciences, it initially affected a number of biomedical research fields such as cancer genomics and clinical genetics. Now, however, a new “wave” of genomic bioinformation is transforming a widening array of disciplines, including those that address the social, historical and cultural dimensions of human life. Increasingly, bioinformation is affecting “human sciences” such as psychiatry, psychology, brain research, behavioural research (“behavioural genomics”), but also anthropology and archaeology (“bioarchaeology”). Thus, bioinformatics is having (...) an impact on how we define and understand ourselves, how identities are formed and constituted, and, finally, on how we (on the basis of these redefined identities) assess and address some of the more concrete societal issues involved in genomics governance in various settings. This article explores how genomics and bioinformation, by influencing research agendas in the human sciences and the humanities, are affecting our self-image, our identity, the way we see ourselves. The impact of bioinformation on self-understanding will be assessed on three levels: (1) the collective level (the impact of comparative genomics on our understanding of human beings as a species), (2) the individual level (the impact of behavioural genomics on our understanding of ourselves as individuals), and (3) the genealogical level (the impact of population genomics on our understanding of human history, notably early human history). This threefold impact will be assessed from two seemingly incompatible philosophical perspectives, namely a “humanistic” perspective (represented in this article by Francis Fukuyama) and a “post-humanistic” one (represented by Peter Sloterdijk). On the basis of this analysis it will be concluded that, rather than focussing on human “enhancement” by adding or deleting genes, genome-oriented practices of the Self will focus on using genomics information in the context of identity-formation. Genomic bioinformation will increasingly be built into our self-images and used in order to tailor and adapt our practices of Self to our “personalised” genome. We will keep working on ourselves, no doubt, not by modifying our genomes, but rather by fine-tuning our behaviour. What we are experiencing is a bioinformatisation of the life-world. Genomics-based technologies will increasingly pervade our daily lives, our autobiographies and narratives, as well as our anthropologies, rather than our genomes as such. (shrink)

Several features of the yeast mitochondrial genome, including high mutation rate, dynamic genomic structure, small effective population size, and dispensability for cellular viability, make it a promising candidate for generating hybrid incompatibility and driving speciation. Cytonuclear incompatibility, a specific type of Dobzhansky‐Muller genetic incompatibility caused by improper interactions between mitochondrial and nuclear genomes, has previously been observed in a variety of organisms, yet its role in speciation remains obscure. Recent studies in Saccharomyces yeast species provide a (...) new insight, with experimental evidence that cytonuclear incompatibility and DNA sequence divergence are both causes of the reproductive isolation of different yeast species. Interestingly, these two mechanisms seem to be perfectly complementary to each other in terms of their effects and evolutionary trajectories. Direct molecular analyses of the incompatible genes in yeasts have started to shed light on the evolutionary forces driving speciation. Editor's suggested further reading in BioEssaysThe cytoplasmic structure hypothesis for ribosome assembly, vertical inheritance, and phylogeny AbstractMitochondrial bioenergetics as a major motive force of speciation Abstract. (shrink)

Engineered microbes are of great potential utility in biotechnology and basic research. In principle, a cell can be built from scratch by assembling small molecule sets with auto‐catalytic properties. Alternatively, DNA can be isolated or directly synthesized and molded into a synthetic genome using existing genomic blueprints and molecular biology tools. Activating such a synthetic genome will yield a synthetic cell. Here we examine obstacles associated with this latter approach using a model system whereby a donor genome (...) from H. influenzae is fragmented, and the pieces are then modified and reassembled stepwise in an E. coli host cell. There are obstacles associated with this strategy related to DNA transfer, DNA replication, cross‐talk in gene regulation and compatibility of gene products between donor and host. Encouragingly, analysis of gene expression indicates widespread transcription of H. influenzae genes in E. coli, and analysis of gap locations in H. influenzae and other microbial genome assemblies reveals few genes routinely incompatible with E. coli. In conclusion, rebuilding and booting a genome remains a feasible and pragmatic approach to creating a synthetic microbial cell. BioEssays 29:580–590, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

The Bermuda Principles for DNA sequence data sharing are an enduring legacy of the Human Genome Project. They were adopted by the HGP at a strategy meeting in Bermuda in February of 1996 and implemented in formal policies by early 1998, mandating daily release of HGP-funded DNA sequences into the public domain. The idea of daily sharing, we argue, emanated directly from strategies for large, goal-directed molecular biology projects first tested within the “community” of C. elegans researchers, and were (...) introduced and defended for the HGP by the nematode biologists John Sulston and Robert Waterston. In the C. elegans community, and subsequently in the HGP, daily sharing served the pragmatic goals of quality control and project coordination. Yet in the HGP human genome, we also argue, the Bermuda Principles addressed concerns about gene patents impeding scientific advancement, and were aspirational and flexible in implementation and justification. They endured as an archetype for how rapid data sharing could be realized and rationalized, and permitted adaptation to the needs of various scientific communities. Yet in addition to the support of Sulston and Waterston, their adoption also depended on the clout of administrators at the US National Institutes of Health and the UK nonprofit charity the Wellcome Trust, which together funded 90% of the HGP human sequencing effort. The other nations wishing to remain in the HGP consortium had to accommodate to the Bermuda Principles, requiring exceptions from incompatible existing or pending data access policies for publicly funded research in Germany, Japan, and France. We begin this story in 1963, with the biologist Sydney Brenner’s proposal for a nematode research program at the Laboratory of Molecular Biology at the University of Cambridge. We continue through 2003, with the completion of the HGP human reference genome, and conclude with observations about policy and the historiography of molecular biology. (shrink)

The fundamental Hennigian principle, grouping solely on synapomorphy, is seldom used in modern phylogenetics. In the submitted paper, we apply this principle in reanalyzing five datasets comprising 197 complete plastid genomes (plastomes). We focused on the latter because plastome-based DNA sequence data gained dramatic popularity in molecular systematics during the last decade. We show that pattern-cladistic analyses based on complete plastid genome sequences can successfully resolve affinities between plant taxa, simultaneously simplifying both the genomic and analytical frameworks of (...) phylogenetic studies. We developed “Matrix to Newick” (M2N), a program to represent the standard molecular alignment of plastid genomes in the form of trees or relationships directly. Thus, massive plastome-based DNA sequence data can be successfully represented in a relational form rather than as a standard molecular alignment. Application of methods of median supertree construction (the Average Consensus method has been used as an example in this study) or Maximum Parsimony analysis to relational representations of plastome sequence data may help systematist to avoid the complicated assumption-based frameworks of Maximum Likelihood or Bayesian phylogenetics that are most used today in massive plastid sequence data analyses. We also found that significant amounts of pure genomic information that typically accommodate the majority of current plastid phylogenomic studies can be effectively dropped by systematists if they focus on the pattern-cladistics or relational analyses of plastome-based molecular data. The proposed pattern-cladistic approach is a powerful and straightforward heuristic alternative to modern plastome-based phylogenetics. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Kennedy Institute of Ethics Journal 14.1 (2004) 47-54 [Access article in PDF] Ethical Guidelines for Human Embryonic Stem Cell Research*(A Recommended Manuscript) Adopted on 16 October 2001Revised on 20 August 2002 Ethics Committee of the Chinese National Human Genome Center at Shanghai, Shanghai 201203 Human embryonic stem cell (ES) research is a great project in the frontier of biomedical science for the twenty-first century. Be- cause the research (...) involves the use of human embryos, it triggers serious debate on ethical issues. Opponents consider the embryo to be an early form of human life that should be respected and not destroyed. However, the majority of scientists support embryonic stem cell research, believing that it offers good prospects for the treatment of diseases that have remained incurable until now and so will benefit humankind. The Ethics Committee of the Department of Ethical, Legal, and Social Implications of the Chinese National Human Genome Center at Shanghai seriously discussed the ethical debate initiated by embryonic stem cell research. We concluded that we should support the scientists of our country in actively carrying out human embryonic stem cell research for the noble cause of "medicine being a beneficent art." For the healthy and orderly development of human embryonic stem cell research in our country, we put forward the following recommended Ethical Guidelines for Human Embryonic Stem Cell Research as a reference for leaders, administrative departments, and related scientists. Preface Article 1. Human embryonic stem cells are the primitive cells that play the main role in the growth and development of a human body. These [End Page 47] primitive cells have the potential for infinite proliferation, self-renewal, and multi-directional differentiation. If scientists can discover the mechanism of differentiation of human embryonic stem cells, it will be possible to induce differentiation of human embryonic stem cells to form various types of human cells for clinical cell therapy. If human embryonic stem cell research can be integrated with modern biomedical engineering techniques, it also will be possible to make repair and replacement of human tissues and organs a reality. Article 2. There are two ways to classify human embryonic stem cells. One way is to classify them according to their potential for differentiation. There could be three kinds of stem cells: totipotent stem cells, pluripotent stem cells, and unipotent stem cells.A totipotent stem cell has the potential to develop into a whole individual. It can differentiate into the more than 200 cell types in the whole body, construct any tissue or organ of the body, and finally develop into a whole individual. The fertilized egg and the cleavage cells at the very early stage of embryonic development are totipotent stem cells.A pluripotent stem cell has the potential to differentiate into many cell types derived from the three embryonic layers. However, it has lost the capacity to develop into a complete organism.A unipotent stem cell is derived from the further differentiation of the pluripotent stem cell. It can differentiate only into one cell type such as a hematopoietic stem cell, neural stem cell, and others.The other way is to classify human stem cells according to their source. There could be two kinds of human stem cells: embryonic stem cells and tissue stem cells (also called adult stem cells). The former involves experimentation with embryos, which has serious ethical implications. Ethical issues associated with the latter are mainly expressed in the various opinions regarding the allocation of health resources. Article 3. Human embryonic stem cells are the group of cells called the blastocyst inner cell mass during the early stage of embryonic development. They are the main source of totipotent stem cells, and hence the focal and hot point in stem cell research. Studies on the clinical application of embryonic stem cells probably will involve use of the somatic cell nucleus transfer (SCNT) technique, which destroys the early human embryo. At present, the ethical and moral debate is very serious in human embryonic stem cell research regarding whether the research will develop... (shrink)

Admixture, the genetic exchange between differentiated populations appears to be common in the history of species, but has not yet been comparatively studied across mammals. This limits the understanding of its mechanisms and potential role in mammalian evolution. The authors want to summarize the current knowledge on admixture in non‐human primates, and suggest that it is important to establish a comparative framework for this phenomenon in humans. Genetic observations in domesticated mammals and their wild counterparts are discussed, and a brief (...) global overview on other clades is presented. Based on this, some of the consequences of gene flow, including incompatibilities and their genomic footprint, as well as adaptive introgression are discussed, and suggestions for a functional genomics approach are made. It is proposed that the field is moving beyond descriptive observations in single species, to a comprehensive analysis of admixture and its impact. Admixture is becoming an integral part of mammalian evolution. (shrink)

Admixture, the genetic exchange between differentiated populations appears to be common in the history of species, but has not yet been comparatively studied across mammals. This limits the understanding of its mechanisms and potential role in mammalian evolution. The authors want to summarize the current knowledge on admixture in non‐human primates, and suggest that it is important to establish a comparative framework for this phenomenon in humans. Genetic observations in domesticated mammals and their wild counterparts are discussed, and a brief (...) global overview on other clades is presented. Based on this, some of the consequences of gene flow, including incompatibilities and their genomic footprint, as well as adaptive introgression are discussed, and suggestions for a functional genomics approach are made. It is proposed that the field is moving beyond descriptive observations in single species, to a comprehensive analysis of admixture and its impact. Admixture is becoming an integral part of mammalian evolution. (shrink)

Alternative ways to ensure mate compatibility, such as hermaphroditism and the breakdown of self‐incompatibility, evolved repeatedly when finding a mating partner is difficult. In a variety of microorganisms where compatibility is determined by mating‐types, a highly regulated form of universal compatibility system called mating‐type switching has evolved several times. This sophisticated system allows for the genetic adjustment of the mating type during asexual growth, and it most likely evolved for reproductive assurance of immotile species under low densities. In this (...) review, we compare the switching strategy to other universal compatibility systems such as “unisexual mating” and homothallism. We identify the costs of switching, including genome instability, and mechanistic costs, as well as the benefits, mainly the maintenance of important mating‐type functions. Given the potential benefits of mating‐type switching, we speculate that switching is likely to have evolved many times independently, and may be more common in groups where genetic mating types regulate mate compatibility than assumed so far. (shrink)

Comparative mapping and sequencing show that turnover of sex determining genes and chromosomes, and sex chromosome rearrangements, accompany speciation in many vertebrates. Here I review the evidence and propose that the evolution of therian mammals was precipitated by evolution of the male‐determining SRY gene, defining a novel XY sex chromosome pair, and interposing a reproductive barrier with the ancestral population of synapsid reptiles 190 million years ago (MYA). Divergence was reinforced by multiple translocations in monotreme sex chromosomes, the first of (...) which supplied a novel sex determining gene. A sex chromosome‐autosome fusion may have separated eutherians (placental mammals) from marsupials 160 MYA. Another burst of sex chromosome change and speciation is occurring in rodents, precipitated by the degradation of the Y. And although primates have a more stable Y chromosome, it may be just a matter of time before the same fate overtakes our own lineage. (shrink)

Many people have argued that the evolution of the human language faculty cannot be explained by Darwinian natural selection. Chomsky and Gould have suggested that language may have evolved as the by-product of selection for other abilities or as a consequence of as-yet unknown laws of growth and form. Others have argued that a biological specialization for grammar is incompatible with every tenet of Darwinian theory – that it shows no genetic variation, could not exist in any intermediate forms, confers (...) no selective advantage, and would require more evolutionary time and genomic space than is available. We examine these arguments and show that they depend on inaccurate assumptions about biology or language or both. Evolutionary theory offers clear criteria for when a trait should be attributed to natural selection: complex design for some function, and the absence of alternative processes capable of explaining such complexity. Human language meets these criteria: Grammar is a complex mechanism tailored to the transmission of propositional structures through a serial interface. Autonomous and arbitrary grammatical phenomena have been offered as counterexamples to the position that language is an adaptation, but this reasoning is unsound: Communication protocols depend on arbitrary conventions that are adaptive as long as they are shared. Consequently, language acquisition in the child should systematically differ from language evolution in the species, and attempts to analogize them are misleading. Reviewing other arguments and data, we conclude that there is every reason to believe that a specialization for grammar evolved by a conventional neo-Darwinian process. (shrink)

Many people have argued that the evolution of the human language faculty cannot be explained by Darwinian natural selection. Chomsky and Gould have suggested that language may have evolved as the by-product of selection for other abilities or as a consequence of as-yet unknown laws of growth and form. Others have argued that a biological specialization for grammar is incompatible with every tenet of Darwinian theory – that it shows no genetic variation, could not exist in any intermediate forms, confers (...) no selective advantage, and would require more evolutionary time and genomic space than is available. We examine these arguments and show that they depend on inaccurate assumptions about biology or language or both. Evolutionary theory offers clear criteria for when a trait should be attributed to natural selection: complex design for some function, and the absence of alternative processes capable of explaining such complexity. Human language meets these criteria: Grammar is a complex mechanism tailored to the transmission of propositional structures through a serial interface. Autonomous and arbitrary grammatical phenomena have been offered as counterexamples to the position that language is an adaptation, but this reasoning is unsound: Communication protocols depend on arbitrary conventions that are adaptive as long as they are shared. Consequently, language acquisition in the child should systematically differ from language evolution in the species, and attempts to analogize them are misleading. Reviewing other arguments and data, we conclude that there is every reason to believe that a specialization for grammar evolved by a conventional neo-Darwinian process. (shrink)

To construct a synthetic cell we need to understand the rules that permit life. A central idea in modern biology is that in addition to the four entities making reality, matter, energy, space and time, a fifth one, information, plays a central role. As a consequence of this central importance of the management of information, the bacterial cell is organised as a Turing machine, where the machine, with its compartments defining an inside and an outside and its metabolism, reads and (...) expresses the genetic program carried by the genome. This highly abstract organisation is implemented using concrete objects and dynamics, and this is at the cost of repeated incompatibilities (frustration), which need to be sorted out by appropriate «patches». After describing the organisation of the genome into the paleome (sustaining and propagating life) and the cenome (permitting life in context), we describe some chemical hurdles that the cell as to cope with, ending with the specific case of the methionine salvage pathway. (shrink)

In birds and frogs, species pairs retain the capacity to produce viable hybrids for tens of millions of years, an order of magnitude longer than mammals. What accounts for these differences in relative rates of pre- and postzygotic isolation? We propose that reproductive mode is a critically important but previously overlooked factor in the speciation process. Viviparity creates a post-fertilization arena for genomic conflicts absent in egg-laying species. With viviparity, conflict can arise between: mothers and embryos; sibling embryos in the (...) womb, and maternal and paternal genomes within individual embryos. Such intra- and intergenomic conflicts result in perpetual antagonistic coevolution, thereby accelerating interpopulation postzygotic isolation. In addition, by generating intrapopulation genetic incompatibility, viviparity-driven conflict favors polyandry and limits the potential for precopulatory divergence. Mammalian diversification is characterized by rapid evolution of incompatible feto-maternal interactions, asymmetrical postzygotic isolation, disproportionate effects of genomically-imprinted genes, and “F2 hybrid enhancement.” The viviparity-driven conflict hypothesis provides a parsimonious explanation for these patterns in mammalian evolution. BioEssays 22:938–946, 2000. © 2000 John Wiley & Sons, Inc. (shrink)

The fitness of a eukaryote hinges on the coordinated function of the products of its nuclear and mitochondrial genomes in achieving oxidative phosphorylation. I propose that sexual selection plays a key role in the maintenance of mitonuclear coadaptation across generations because it enables pre-zygotic sorting for coadapted mitonuclear genotypes. At each new generation, sexual reproduction creates new combinations of nuclear and mitochondrial genes, and the potential arises for mitonuclear incompatibilities and reduced fitness. In reviewing the literature, I hypothesize that individuals (...) engaged in mate choice select partners with correct species-typical mitochondrial and nuclear genotypes as well as individuals with highly functional cellular respiration. The implication is that mate choice for compatible nuclear and mitochondrial genes can play a significant role in generating the patterns of ornamentation and preferences observed in animals. A number of testable predictions emerge from this mitonuclear compatibility hypothesis of sexual selection. Products of mitochondrial and nuclear genes co-function to enable cellular respiration, so it is critical that compatible mitochondrial and nuclear genes be matched each generation. I propose that a core function of mate choice is selection for mitochondrial and nuclear genes that create compatible and functional combinations in offspring. (shrink)

We suggest that supergenes, groups of co‐inherited loci, may be involved in a range of intriguing genetic and evolutionary phenomena in insect societies, and may play broad roles in the evolution of cooperation and conflict. Supergenes are central in the evolution of an array of traits including self‐incompatibility, mimicry, and sex chromosomes. Recently, researchers identified a large supergene, described as a social chromosome, which controls social organization in the fire ant. This system was previously considered to be a remarkable (...) example of a single gene affecting a complex social trait. We describe how selection may commonly favor reduced recombination and the formation of supergenes for social traits, and once formed, supergenes may strongly influence further evolutionary dynamics within and between lineages. The evolution of supergenes, and even wholly non‐recombining genomes, may be particularly common in systems in which genetically distinct lineages can form mutually reinforcing socially parasitic relationships. (shrink)

The Modern Synthesis was based on Darwin’s gradualist view of evolution and early twentieth Century Mendelian and population genetics. Although early results in microbial and molecular genetics seemed to solidify MS views through the Central Dogma of Molecular Biology, accepting their basic concepts as permanent truths blinded MS proponents to the importance of incompatible discoveries in the second half of the 20th and early 21st Centuries. Discoveries based largely on the DNA record have provided a radically different view of (...) class='Hi'>genome complexity and biologically-mediated evolutionary change. (shrink)

Recent experimental data from proteomics and genomics are interpreted here in ways that challenge the predominant viewpoint in biology according to which the four evolutionary processes, including mutation, recombination, natural selection and genetic drift, are sufficient to explain the origination of species. The predominant viewpoint appears incompatible with the finding that the sequenced genome of each species contains hundreds, or even thousands, of unique genes - the genes that are not shared with any other species. These unique genes and (...) proteins, singletons, define the very character of every species. Moreover, the distribution of protein families from the sequenced genomes indicates that the complexity of genomes grows in a manner different from that of self-organizing networks: the dominance of singletons leads to the conclusion that in living organisms a most unlikely phenomenon can be the most common one. In order to provide proper rationale for these conclusions related to the singletons, the paper first treats the frequency of functional proteins among random sequences, followed by a discussion on the protein structure space, and it ends by questioning the idea that protein domains represent conserved units of evolution. (shrink)

In the heterothallic species Neurospora crassa, strains of opposite mating type, A and a, must interact to give the series of events resulting in fruiting body formation, meiosis, and the generation of dormant ascospores. The mating type of a strain is specified by the DNA sequence it carries in the mating type region; strains that are otherwise isogenic can mate and produce ascospores. The DNA of the A and a regions have completely dissimilar sequences. Probing DNA from strains of each (...) mating type with labelled sequences from the A and the a regions has shown that, unlike in Saccharomyces cerevisiae, only a single copy of a mating type sequence is present in a haploid genome. The failure to switch is explainable by the physical absence of DNA sequences characteristic of the opposite mating type. While the mating type sequences must be of the opposite kind for mating to occur in the sexual cycle, two strains of opposite mating type cannot form a stable heterokaryon during vegetative growth; instead, they fuse abortively to give a heterokaryon incompatibility reaction, which results in death of the cells along the fusion line. The DNA sequences responsible for this reaction are coextensive with those sequences in the A and a regions which are necessary to initiate fruiting body formation. The genus Neurospora also includes homothallic species – ones in which a single haploid nucleus carries all the information necessary to form fruiting bodies, undergo meiosis, and produce new haploid spores. One such species, N. terricola, contains one copy each of the A and the a sequences within each haploid genome. Another homothallic species, N. africana, contains a single copy of the A sequence in the haploid genome, but does not contain any sequences corresponding to the a sequence. We present a model for the role of the mating type‐specific sequences in heterothallic and homothallic species of Neurospora and we speculate on the origin of the different modes of reproduction in the genus Neurospora. (shrink)

In Evangelium vitae, Pope St. John Paul II recognized that scientific progress would bring about new attacks on the dignity of the human person. Since that time, remarkable expansion in our knowledge and understanding of the human genome has brought forth questions of ownership rights via patents on human genes and related technology. This article argues that patenting human genes is incompatible with human dignity as it commodifies that which is priceless. In contrast, granting patents to manipulations of human (...) genes does not violate human dignity so long as it is utilized toward the common good. National Catholic Bioethics Quarterly 15.2 : 265–285. (shrink)

Currently, the concept of the cell as a society or an ecosystem of molecular elements is gaining increasing acceptance. The basic idea arose in the 19th century, from the surmise that there is not just a single unit underlying an individual’s appearance, but a plurality of entities with both collaborative and conflicting relationships. The following hypothesis is based around this model. The incompatible activities taking place between different original elements, which were subsumed into the first cell and could not be (...) eliminated, had to be controlled very closely. Similarly, a strong level of control had to be developed over many cellular elements after the cell changed its genome to DNA. We assume that at least some of those original RNA agents and other biomolecules which carry incompatibilities and risks, are retained within current cells, although they are now under strict control. A virus functions as a signal informing these repressed cellular RNAs and other elements of ancient origin how to restore suppressed degrees of molecular freedom, favoring pre-existing molecular affinities and activities, re-establishing ancient molecular webs of interactions, and giving fragments of ancient coded information the opportunity to be re-expressed. Collectively, these newly activated mechanisms lead to different possibilities for pathological cell states. All these processes are opposed by cell-control mechanisms. Thus, in this new scenario, the battle is considered intracellular rather than between the virus and the cell. And so the virus is treated as the signal that precipitates the cell’s change from a latent to an active pathological state. (shrink)

The prospect of using genome technologies to modify the human germline has raised profound moral disagreement but also emphasizes the need for wide-ranging discussion and a well-informed policy response. The Hinxton Group brought together scientists, ethicists, policymakers, and journal editors for an international, interdisciplinary meeting on this subject. This consensus statement formulated by the group calls for support of genome editing research and the development of a scientific roadmap for safety and efficacy; recognizes the ethical challenges involved in (...) clinical reproductive applications of genome editing but, importantly, rejects the idea that human reproductive germline modification is necessarily morally unacceptable; and highlights the importance of meaningful engagement in discussions of genome editing and the development of regulation and oversight mechanisms to govern future uses of such technologies. (shrink)

In this paper, I will present the empirical version of the slippery slope argument (SSA) in the field of genome editing. According to the SSA, if we adopt germline manipulation of embryos we will eventually end up performing or allowing something morally reprehensible, such as new coercive eugenics. I will investigate the actual possibility of sliding towards eugenics: thus, I will examine enhancement and eugenics both in the classical and liberal versions, through the lens of SSA. In the first (...) part, I will discuss the classical eugenics from a historical perspective and conclude that classical eugenics is morally deplorable; but by currently accepting genome editing I argue that it is not possible to ‘slip’ into classical eugenics. Then, I will analyze liberal eugenics: I will consider Habermas’ and Sandel’s objections to liberal eugenics and genetic human enhancement. Subsequently, I will reply to these arguments affirming that, although it is not possible to refuse any form of genetic enhancement, liberal eugenics would not consider the principles of justice, non-maleficence, and non-instrumentalization; hence, it should be considered not morally acceptable. In addition, I will support the thesis according to which the possibility of relapsing into liberal eugenics is more likely than relapsing into classical eugenics. Then, I will present a strategy that, while avoiding falling into the undesirable scenarios related to SSA, still accepts some application of germline genome editing of embryos and gametes. In such a way, I will show that even if we accept the plausibility of a certain slip into an undesirable scenario, SSA does not offer conclusive reasons to forbid any use of germline genome editing technique in both therapeutic and enhancement fields. (shrink)

As genomic science has evolved, so have policy and practice debates about how to describe and evaluate the ways in which genomic information is treated for individuals, institutions, and society. The term genetic exceptionalism, describing the concept that genetic information is special or unique, and specifically different from other kinds of medical information, has been utilized widely, but often counterproductively in these debates. We offer genomic contextualism as a new term to frame the characteristics of genomic science in the debates. (...) Using stasis theory to draw out the important connection between definitional issues and resulting policies, we argue that the framework of genomic contextualism is better suited to evaluating genomics and its policy-relevant features to arrive at more productive discussion and resolve policy debates. (shrink)

CRISPR is widely considered to be a disruptive technology. However, when it comes to the most controversial topic, germline genome editing (GGE), there is no consensus on whether this technology has any substantial advantages over existing procedures such as embryo selection after in vitro fertilization (IVF) and preimplantation genetic diagnosis (PGD). Answering this question, however, is crucial for evaluating whether the pursuit of further research and development on GGE is justified. This paper explores the question from both a clinical (...) and a moral viewpoint, namely whether GGE has any advantages over existing technologies of selective reproduction and whether GGE could complement or even replace them. In a first step, I review an argument of extended applicability. The paper confirms that there are some scenarios in which only germline intervention allows couples to have (biologically related) healthy offspring, because selection will not avoid disease. In a second step, I examine possible moral arguments in favour of genetic modification, namely that GGE could save some embryos and that GGE would provide certain benefits for a future person that PGD does not. Both arguments for GGE have limitations. With regard to the extended applicability of GGE, however, a weak case in favour of GGE should still be made. (shrink)

Ethical statements and position papers on genome editing often refer to “the public” that should get involved, and a public discussion that should take place. It is not self-evident what this reference to the public means and why such a public engagement should take place. This chapter explores the concept of the public as discussed in key position papers on genome editing and puts it into relationship with the notion of the public in political theory. The fuzzy notion (...) of the public is presented in these statements on genome editing as a tool to solve problems and to allow for hitherto unheard points of view to be considered. It is sometimes understood as a general tool for reciprocal education and social self-determination. Other times still it is used in an instrumental way to gain public support and foster an environment friendly to research and innovation. There is disagreement about the aims, the reason, and the norms guiding public discussion and the possibility of a neutral form of communication. Last but not least awareness is required for the way the public debate is framed by the very use of “genome” and “editing” rather than other concepts. (shrink)

The introduction of genomics and biobanking methodologies to the African research context has also introduced novel ways of doing science, based on values of sharing and reuse of data and samples. This shift raises ethical challenges that need to be considered when research is reviewed by ethics committees, relating for instance to broad consent, the feedback of individual genetic findings, and regulation of secondary sample access and use. Yet existing ethics guidelines and regulations in Africa do not successfully regulate research (...) based on sharing, causing confusion about what is allowed, where and when. In order to understand better the ethics regulatory landscape around genomic research and biobanking, we conducted a comprehensive analysis of existing ethics guidelines, policies and other similar sources. We sourced 30 ethics regulatory documents from 22 African countries. We used software that assists with qualitative data analysis to conduct a thematic analysis of these documents. Surprisingly considering how contentious broad consent is in Africa, we found that most countries allow the use of this consent model, with its use banned in only three of the countries we investigated. In a likely response to fears about exploitation, the export of samples outside of the continent is strictly regulated, sometimes in conjunction with regulations around international collaboration. We also found that whilst an essential and critical component of ensuring ethical best practice in genomics research relates to the governance framework that accompanies sample and data sharing, this was most sparingly covered in the guidelines. There is a need for ethics guidelines in African countries to be adapted to the changing science policy landscape, which increasingly supports principles of openness, storage, sharing and secondary use. Current guidelines are not pertinent to the ethical challenges that such a new orientation raises, and therefore fail to provide accurate guidance to ethics committees and researchers. (shrink)

One of the main fields of research in genome editing is the manufacture of transgenic organisms. If this includes genetically human components, then we must not only ask whether such techniques should be allowed, but also what the moral status of “cross species beings” with a genetically “human” component would be and whether the possibility to manufacture them affects the validity of bioethical arguments from species affiliation. In my chapter I want to show that the two latter questions are (...) less dramatic than it might seem, because most, if not all transgenic organisms are not real “interspecies beings”, but rather belong to one of the original species, or constitute a new species. As for the first question, possible epistemic uncertainties about the status of transgenic organisms call for a precautionary approach. (shrink)

This paper is intended to complement our previous works on the necessary existence of error-correcting codes endowing genomes with the ability of being regenerated, not merely copied. It sketchily recalls some fundamental definitions and results of information theory and error-correcting codes; provides an overview of our research; shows that the disjunction of replication and regeneration enlightens the divide between germinal and somatic cells; suggests that some phenomena referred to as epigenetic may possibly find an explanation within the framework of error-correcting (...) codes; points out some difficulties, especially those related to sexual reproduction; criticizes the template-replication paradigm, and prompts geneticists to become familiar with information theory. (shrink)

This paper explores the ethics of introducing genome-editing technologies as a new reproductive option. In particular, it focuses on whether genome editing can be considered a morally valuable alternative to preimplantation genetic diagnosis. Two arguments against the use of genome editing in reproduction are analysed, namely safety concerns and germline modification. These arguments are then contrasted with arguments in favour of genome editing, in particular with the argument of the child’s welfare and the argument of parental (...) reproductive autonomy. In addition to these two arguments, genome editing could be considered as a worthy alternative to PGD as it may not be subjected to some of the moral critiques moved against this technology. Even if these arguments offer sound reasons in favour of introducing genome editing as a new reproductive option, I conclude that these benefits should be balanced against other considerations. More specifically, I maintain that concerns regarding the equality of access to assisted reproduction and the allocation of scarce resources should be addressed prior to the adoption of genome editing as a new reproductive option. (shrink)

Whole-genome analysis and whole-exome analysis generate many more clinically actionable findings than traditional targeted genetic analysis. These findings may be relevant to research participants themselves as well as for members of their families. Though researchers performing genomic analyses are likely to find medically significant genetic variations for nearly every research participant, what they will find for any given participant is unpredictable. The ubiquity and diversity of these findings complicate questions about disclosing individual genetic test results. We outline an approach (...) for disclosing a select range of genetic results to the relatives of research participants who have died, developed in response to relatives? requests during a pilot study of large-scale medical genetic sequencing. We also argue that studies that disclose individual research results to participants should, at a minimum, passively disclose individual results to deceased participants? relatives. (shrink)

1900 was a remarkable year for science. Several ground-breaking events took place, in physics, biology and psychology. Planck introduced the quantum concept, the work of Mendel was rediscovered, and Sigmund Freud published The Interpretation of Dreams . These events heralded the emergence of completely new areas of inquiry, all of which greatly affected the intellectual landscape of the 20 th century, namely quantum physics, genetics and psychoanalysis. What do these developments have in common? Can we discern a family likeness, a (...) basic affinity between them, so that we can use the one to deepen our understanding of the other? One common denominator is that they open up realms of inquiry that are significantly different from the world of everyday experience, namely the realm of elementary particles, of genes and genomes, and of the unconscious. But to what extent can we meaningfully argue, for instance, that the genome is the biological unconscious, and the unconscious the psychic genome? To address these questions, I will build on the work of two key intellectual figures who have explored the affinities of these developments in depth, namely Erwin Schrödinger (a quantum physicist and avid reader of Schopenhauer who initiated molecular biology) and Jacques Lacan (who reframed the specificity of psychoanalysis with the help of 20 th century science: the era of structural linguistics, but also of quantum physics, molecular biology, bioinformatics and DNA). (shrink)

How should we regulate genome editing in the face of persistent substantive disagreement about the moral status of this technology and its applications? In this paper, we aim to contribute to resolving this question. We first present two diametrically opposed possible approaches to the regulation of genome editing. A first approach, which we refer to as “elitist,” is inspired by Joshua Greene’s work in moral psychology. It aims to derive at an abstract theoretical level what preferences people would (...) have if they were committed to implementing public policies regulating genome editing in a context of ethical pluralism. The second approach, which we refer to as the democratic approach, defended by Francoise Baylis and Sheila Jasanoff et al., emphasizes the importance of including the public’s expressed attitudes in the regulation of genome editing. After pointing out a serious shortcoming with each of these approaches, we propose our own favored approach—the “enlightened democracy” approach—which attempts to combine the strengths of the elitist and democratic approaches while avoiding their weaknesses. (shrink)

In this paper I argue that some human reproductive genome editing interventions can be therapeutic in nature, and thus that it is false that all such interventions just create healthy individuals. I do this by showing that the conditions established by a therapy definition are met by certain reproductive genome editing interventions. I then defend this position against two objections: (a) reproductive genome editing interventions do not attain one of the two conditions for something to be a (...) therapy, and (b) some reproductive genome editing interventions are therapeutic but in a nonstandard way. In the Conclusion I call for a more nuanced discussion of the nature of reproductive genome editing interventions. (shrink)

It is frequently said that biology is emerging from a long phase of reductionism. It would be certainly more correct to say that biologists are abandoning a certain form of reductionism. We describe this past form, and the experiments which challenged the previous vision. To face the difficulties which were met, biologists use a series of concepts and metaphors - pleiotropy, tinkering, epigenetics - the ambiguity of which masks the difficulties, instead of solving them. In a similar way, the word (...) “post-genomics” has different meanings, depending upon who uses it. Which of these meanings will become dominant in the future is an open question. (shrink)

Biotechnology might contribute to solving food safety and security challenges. However, gene technology has been under public scrutiny, linked to the framing of the media and public discourse. The study aims to investigate people’s perceptions and acceptance of food biotechnology with focus on transgenic genetic modification versus genome editing. An online experiment was conducted with participants from the United Kingdom and Switzerland. The participants were presented with the topic of food biotechnology and more specifically with experimentally varied vignettes on (...) transgenic and genetic modification and genome editing. The results suggest that participants from both countries express higher levels of acceptance for genome editing compared to transgenic genetic modification. The general and personal acceptance of these technologies depend largely on whether the participants believe the application is beneficial, how they perceive scientific uncertainty, and the country they reside in. Our findings suggest that future communication about gene technology should focus more on discussing trade-offs between using an agricultural technologies and tangible and relevant benefits, instead of a unidimensional focus on risk and safety. (shrink)

In this paper, I defend McKinsey's argument (Analysis 1991) that Burge's antiindividualist position is incompatible with privileged access, viz. the claim that each subject can know his own thought contents just by reflection and without having undertaken an empirical investigation. I argue that Burge thinks that there are certain necessary conditions for a subject to have thoughts involving certain sorts of concepts; these conditions are appropriately different for thoughts involving natural kind concepts and thoughts involving non-natural kind concepts. I use (...) Burge's commitment to these entailments to show that his antiindividualist position is incompatible with privileged access. (shrink)

Genomics is increasingly becoming an integral component of health research and clinical care. The perceived difficulties associated with genetic research involving Aboriginal and Torres Strait Islander people mean that they have largely been excluded as research participants. This limits the applicability of research findings for Aboriginal and Torres Strait Islander patients. Emergent use of genomic technologies and personalised medicine therefore risk contributing to an increase in existing health disparities unless urgent action is taken. To allow the potential benefits of genomics (...) to be more equitably distributed, and minimise potential harms, we recommend five actions: ensure diversity of participants by implementing appropriate protocols at the study design stage; target diseases that disproportionately affect disadvantaged groups; prioritise capacity building to promote Indigenous leadership across research professions; develop resources for consenting patients or participants from different cultural and linguistic backgrounds; and integrate awareness of issues relating to Indigenous people into the governance structures, formal reviews, data collection protocols and analytical pipelines of health services and research projects. (shrink)

Somatic diversification of antigen receptor genes depends on the activity of enzymes whose homologs participate in a mutagenic DNA repair in unicellular species. Indeed, by engaging error-prone polymerases, gap filling molecules and altered mismatch repair pathways, lymphocytes utilize conserved components of genomic stress response systems, which can already be found in bacteria and archaea. These ancient systems of mutagenesis and repair act to increase phenotypic diversity of microbial cell populations and operate to enhance their ability to produce fit variants during (...) stress. Coopted by lymphocytes, the ancient mutagenic processing systems retained their diversification functions instilling the adaptive immune cells with enhanced evolvability and defensive capacity to resist infection and damage. As reviewed here, the ubiquity and conserved character of specialized variation-generating mechanisms from bacteria to lymphocytes highlight the importance of these mechanisms for evolution of life in general. (shrink)

Recent discussions of genomics and international justice have adopted the concept of ‘global public goods’ to support both the view of genomics as a benefit and the sharing of genomics knowledge across nations. Such discussion relies on a particular interpretation of the global public goods argument, facilitated by the ambiguity of the concept itself. Our aim in this article is to demonstrate this by a close examination of the concept of global public goods with particular reference to its use in (...) the context of genomic databases. We contend that the argument for construing genomics as a global public good depends on seeing it as a natural good by focusing on features intrinsic to genomics knowledge. We shall argue that social and political arrangements are relevant and that recognising this opens the door to construing the use of global public goods language as a strategic one. (shrink)

Retrotransposon-derived elements (RDEs) can disrupt gene expression, but are nevertheless widespread in metazoan genomes. This review presents a hypothesis that repressive RNA-binding proteins (RBPs) facilitate the large-scale accumulation of RDEs. Many RBPs bind RDEs in pre-mRNAs to repress the effects of RDEs on RNA processing, or the formation of inverted repeat RNA structures. RDE-binding RBPs often assemble on extended, multivalent binding sites across the RDE, which ensures repression of cryptic splice or polyA sites. RBPs thereby minimize the effects of RDEs (...) on gene expression, which likely reduces the negative selection against RDEs. While mutations that change splice sites in RDEs act as an off-on switch in exon formation, mutations that decrease the multivalency of RBP binding sites resemble a rheostat that enables a more gradual evolution of new RDE-derived exons. RBPs might also repress aberrant processing of active retrotransposons, thus increasing the chance that full-length copies are made. Taken together, in this review, it is proposed that RBPs facilitate the widespread accumulation of intronic RDEs by repressing RNA processing while chaperoning their potential to gradually evolve into new exons. (shrink)

Genome editing is revolutionising the field of genetics, which includes novel applications to food animals. Responsible research and innovation has been advocated as a way of ensuring that a wider-range of stakeholders and publics are able to engage with new and emerging technologies to inform decision making from their perspectives and values. We posit that genome editing is now proceeding at such a fast rate, and in so many different directions, such as to overwhelm attempts to achieving a (...) more reflective pace. An alternative location for reflection is during the much slower process of taking products from the lab to market. We suggest emphasising Responsible Innovation, putting the ‘I’ back into RRI, and encouraging companies to embrace an RRI approach. We review some previous attempts at developing industry-relevant frameworks for RRI. We then describe two examples of genome editing in livestock; hornless cattle and disease resistant pigs, and reflect on the sorts of questions that could be considered in these two genome editing examples. This paper seeks to take forward the discussion on RRI by extending it to bringing products to market in the context of genome edited livestock. (shrink)

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

In this article, I argue that genomic programs are not substitutes for multi-causal molecular mechanistic explanations of inheritance, but abstract representations of the same sort as mechanism schemas already described in the philosophical literature. On this account, the program analogy is not reductionistic and does not ignore or underestimate the active contribution of epigenetic elements to phenotypes and development. Rather, genomic program representations specifically highlight the genomic determinants of inheritance and their organizational features at work in the wider context of (...) the mechanisms of genome expression. (shrink)