Crespi & Badcock (C&B) provide a novel hypothesis outlining a role for imprinted genes in mediating brain functions underlying social behaviours. The basic premise is that maternally expressed genes are predicted to promote hypermentalistic behaviours, and paternally expressed genes hypomentalistic behaviours. The authors provide a detailed overview of data supporting their ideas, but as we discuss, caution should be applied in interpreting these data.

Humans spend large portions of their time and energy talking to one another, yet it remains unclear whether this activity is primarily selfish or altruistic. Here, it is shown how parent‐of‐origin specific gene expression—or “genomic imprinting”—may provide an answer to this question. First, it is shown why, regarding language, only altruistic or selfish scenarios are expected. Second, it is pointed out that an individual's maternal‐origin and paternal‐origin genes may have different evolutionary interests regarding investment into language, and that (...) this intragenomic conflict may drive genomic imprinting which—as the direction of imprint depends upon whether investment into language is relatively selfish or altruistic—may be used to discriminate between these two possibilities. Third, predictions concerning the impact of various mutations and epimutations at imprinted loci on language pathologies are derived. In doing so, a framework is developed that highlights avenues for using intragenomic conflicts to investigate the evolutionary drivers of language. (shrink)

Genomic conflicts are potentially involved in the evolution and maintenance of culture. Maternal genes contributing to neocortical development could influence biases in the acquisition of information. Specifically, relatedness asymmetries due to multiple paternity are expected to lead to an increased reliability and receptivity of matrilineally-transmitted information. This view complements the gene-culture coevolutionary model adopted by Rendell and Whitehead.

Evidence for recombination suppression has been identified in linkage studies of several unstable DNA diseases. Also sex‐specific changes in recombination frequency have been detected at the loci of Huntington's disease and myotonic dystrophy. It can be hypothesized that meiotic recombination is regulated by genome‐wide genomic imprinting and that changes in meiotic recombination imply the presence of the genomic imprinting defect. If aberrant recombination at the locus of trinucleotide repeat expansion is verified, new theoretical and experimental opportunities (...) will arise in studies on the role of genomic imprinting in the unstable DNA diseases. (shrink)

Different types of explanations coexist in present-day biology. Functional explanations describe mechanisms, whereas evolutionary explanations provide answers to the question “why?” mostly by appealing to the past and present action of natural selection. But the relations between these two types of explanations, as well as the relative insights they offer, vary from one domain of research to another. We will illustrate this complex landscape of biological explanations with three examples involving aging, the sex ratio, and the phenomenon of genomic (...) imprinting. We will show that the two types of explanations have recently often progressed towards each other. In consequence, they cease to be “pure” functional or evolutionary explanations and become explanations that may be alternatively considered as functional or evolutionary. (shrink)

Imprinted genes are monoallelically expressed in a parent‐of‐origin‐specific manner, but for many genes reported to be imprinted, the occurrence of preferential expression—where both alleles are expressed but one is expressed more strongly than the other in a parent‐of‐origin‐specific way—has been reported. This preferential expression found in genes described as imprinted has not been thoroughly addressed in genomic imprinting studies. To study this phenomenon, 50 genes, reported to be imprinted in the mouse, were chosen for investigation. Preferential expression was (...) observed for 21 of 27 maternally expressed genes. However, only 5 of 23 paternally expressed genes showed preferential expression. Recently, it has been reported that a remarkable proportion of non‐imprinted genes show differential allelic expression. If there is overlap between non‐imprinted genes that are differentially expressed and imprinted genes that are preferentially expressed, we need to set new definitions of imprinted genes that, in turn, would probably lead to reassessments of the total number of imprinted genes in mammalian species. BioEssays 29:1022–1028, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Transcriptome sequencing has identified more than a thousand potentially imprinted genes in the mouse brain. This comes as a revelation to someone who cut his teeth on the identification of imprinted genes when only a handful was known. Genomic imprinting, an epigenetic mechanism that determines expression of alleles according to sex of transmitting parent, was discovered over 25 years ago in mice but remains an enigmatic phenomenon. Why do these genes disobey the normal Mendelian logic of inheritance, do (...) they function in specific processes, and how is their imprinting conferred? Next generation sequencing technologies are providing an unprecedented opportunity to survey the whole genome for imprinted genes and are beginning to reveal that imprinting may be more pervasive than we had come to believe. Such advances should lay the foundation for a definitive account of imprinting, but may also challenge accepted views on what it means to be imprinted.Editor's suggested further reading in BioEssays RNA as the substrate for epigenome‐environment interactions Abstract. (shrink)

The basic premise of the host‐defense theory is that genomic imprinting, the parent‐of‐origin expression of a subset of mammalian genes, derives from mechanisms originally dedicated to silencing repeated and retroviral‐like sequences that deeply colonized mammalian genomes. We propose that large clusters of tandemly‐repeated C/D‐box small nucleolar RNAs (snoRNAs) or microRNAs represent a novel category of sequences recognized as “genomic parasites”, contributing to the emergence of genomic imprinting in a subset of chromosomal regions that contain them. (...) Such a view is supported by evidence derived from studies of the imprinted snoRNA‐ and/or miRNA‐encoding Dlk1‐Dio3, Snurf‐Snrpn, Sfbmt2, and C19MC domains. While adding a new piece to the challenging puzzle of mammalian genome history, this hypothesis also reinforces the notion that dissecting the features and molecular mechanisms that discriminate between “foreign” and “endogenous” sequences is of crucial importance in the field of mammalian epigenetics. (shrink)

Crespi & Badcock (C&B) have presented a novel view that the influence of genomic imprinting causes diametrically opposite disorders: namely, psychoses and autism. I propose an extended hypothesis that while genomic imprinting is likely to have an influence on the pathogenesis of psychoses and autism, it might contribute to phenomenological antithesis between as well as within these disorders.

What is the status of the dichotomy proposed and the nosological validity of the contrasting pathologies described in the target article? How plausibly can dysregulated imprinting explain the array of features described, compared with other genetic models? We believe that considering alternative models is more likely to lead in the long term to the correct classification and explanation of the component behaviours.

Current models for regulation of parent‐specific gene expression in plants have been based on a small number of imprinted genes in Arabidopsis. These present repression as the default state, with expression requiring targeted activation. In general, repression is associated with maintenance methylation of cytosines, while no role has been found in Arabidopsis imprinting for de novo methylation—unlike the case in mammals. A recent paper1 both reinforces and challenges the model drawn from Arabidopsis. Methylation patterns of two imprinted loci in (...) maize were tracked from gametes to offspring, enabling an exploration of the timing of imprinting. For one gene, fie1, the results were as expected: parent‐specific methylation patterns were inherited from the three types of gamete: egg, central cell and sperm. The behaviour of fie2, however, was a surprise: no alleles were methylated in the gametes, although paternally contributed fie2 is methylated and silent in the endosperm, indicating that, in some cases, plant imprinting requires de novo DNA methylation. This work significantly broadens our understanding of plant imprinting and points to a greater diversity in imprinting mechanisms than has previously been appreciated. BioEssays 28: 1167–1171, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Rett syndrome (RTT) is an X‐linked dominant neurodevelopmental disorder affecting almost exclusively girls. Although mutations in methyl‐CpG‐binding protein (MeCP2) are known to be associated with RTT, gene expression patterns are not significantly altered in MeCP2‐deficient cells. A recent study1 identified MeCP2‐mediated histone modification and formation of a higher‐order chromatin loop structure specifically associated with silent chromatin at the Dlx5–Dlx6 locus in normal cells, and its absence thereof in RTT patients. This altered expression of Dlx5 through loss of silent chromatin loop (...) formation provides a molecular mechanism underlying RTT and proposes a novel role for MeCP2 in chromatin organization and imprinting. © 2005 Wiley Periodicals, Inc. BioEssays 27:676–680, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

Genomic imprinting is an epigenetic mechanism resulting in the preferential expression of the maternal or paternal alleles of a specific subset of genes in the mammalian genome. A key but relatively unexplored question is how imprints are established in the germline. New observations(1) on two classical imprinting disorders, the Prader‐Willi (PWS) and Angleman (AS) syndromes, offer the first genetic insight into this process. Molecular analysis of imprinting mutations that interfere with the appropriate establishment of the maternal (...) and paternal epigenotypes has led to the identification of imprinted transcripts that could be involved in switching imprints in the germlines. (shrink)

Three recent genome‐wide studies in mice and humans have produced the most definitive map to date of genomic imprinting (gene expression that depends on parental origin) by incorporating multiple tissue types and developmental stages. Here, we explore the results of these studies in light of the kinship theory of genomic imprinting, which predicts that imprinting evolves due to differential genetic relatedness between maternal and paternal relatives. The studies produce a list of imprinted genes with around (...) 120–180 in mice and ∼100 in humans. The studies agree on broad patterns across mice and humans including the complex patterns of imprinted expression at loci like Igf2 and Grb10. We discuss how the kinship theory provides a powerful framework for hypotheses that can explain these patterns. Finally, since imprinting is rare in the genome despite predictions from the kinship theory that it might be common, we discuss evolutionary factors that could favor biallelic expression. (shrink)

The kinship theory of genomic imprinting predicts that imprinted genes affect parent–child and child–child interactions. During prenatal and neonatal stages, patrigenes promote selfish and matrigenes altruistic behavior. Models predict that this imprinted gene expression pattern is reversed starting with the juvenile stage. This article explores possible effects of imprinted genes on nonverbal and simple and complex linguistic behaviors before and after the reversal. A hypothesis is discussed that is based on the observation language evolved as a new form (...) of communicative behavior. Inclusive fitness theory is used for explaining how and why new forms of communicative behaviors evolved as an extension of behaviors and gestures displayed by our predecessors. The hypothesis is elaborated through discussing a scenario of early language evolution. This scenario is used for explaining early stages in child development and for discussing possible effects of patrigenes and matrigenes on the development of children’s communicative behaviors. (shrink)

In contrast to the biallelic expression of most genes, expression of genes subject to genomic imprinting is monoallelic and based on the sex of the transmitting parent. Possession of only a single active allele can lead to deleterious health consequences in humans. Aberrant expression of imprinted genes, through either genetic or epigenetic alterations, can result in developmental failures, neurodevelopmental and neurobehavioral disorders and cancer. The evolutionary emergence of imprinting occurred in a common ancestor to viviparous mammals after (...) divergence from the egg‐laying monotremes. Current evidence indicates that imprinting regulation in metatherian mammals differs from that in eutherian mammals. This suggests that imprinting mechanisms are evolving from those that were established 150 million years ago. Therefore, comparing genomic sequence of imprinted domains from marsupials and eutherians with those of orthologous regions in monotremes offers a potentially powerful bioinformatics approach for identifying novel imprinted genes and their regulatory elements. Such comparative studies will also further our understanding of the molecular evolution and phylogenetic distribution of imprinted genes. BioEssays 25:577–588, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

It is becoming increasingly evident that the driving forces of evolutionary novelty are not randomly derived chance mutations of the genetic text, but a precise genome editing by omnipresent viral agents. These competences integrate the whole toolbox of natural genetic engineering, replication, transcription, translation, genomic imprinting, genomic creativity, enzymatic inventions and all types of genetic repair patterns. Even the non-coding, repetitive DNA sequences which were interpreted as being ancient remnants of former evolutionary stages are now recognized as (...) being of viral descent and crucial for higher-order regulatory and constitutional functions of protein structural vocabulary. In this article I argue that non-randomly derived natural genome editing can be envisioned as (a) combinatorial (syntactic), (b) context-specific (pragmatic) and (c) content-sensitive (semantic) competences of viral agents. These three-leveled biosemiotic competences could explain the emergence of complex new phenotypes in single evolutionary events. After short descriptions of the non-coding regulatory networks, major viral life strategies and pre-cellular viral life three of the major steps in evolution serve as examples: There is growing evidence that natural genome-editing competences of viruses are essential (1) for the evolution of the eukaryotic nucleus, (2) the adaptive immune system and (3) the placental mammals. (shrink)

The H19 gene produces a non‐coding RNA, which is abundantly expressed during embryonic development and down‐regulated after birth. Although this gene was discovered over 20 years ago, its function has remained unclear. Only recently a role was identified for the non‐coding RNA and/or its microRNA partner, first as a tumour suppressor gene in mice, then as a trans‐regulator of a group of co‐expressed genes belonging to the imprinted gene network that is likely to control foetal and early postnatal growth in (...) mice. The mechanisms underlying this transcriptional or post‐transcriptional regulation remain to be discovered, perhaps by identifying the protein partners of the full‐length H19 RNA or the targets of the microRNA. This first in vivo evidence of a functional role for the H19 locus provides new insights into how genomic imprinting helps to control embryonic growth. (shrink)

That there is a heritable or familial component of susceptibility to chronic non‐communicable diseases such as type 2 diabetes, obesity and cardiovascular disease is well established, but there is increasing evidence that some elements of such heritability are transmitted non‐genomically and that the processes whereby environmental influences act during early development to shape disease risk in later life can have effects beyond a single generation. Such heritability may operate through epigenetic mechanisms involving regulation of either imprinted or non‐imprinted genes but (...) also through broader mechanisms related to parental physiology or behaviour. We review evidence and potential mechanisms for non‐genomic transgenerational inheritance of ‘lifestyle’ disease and propose that the ‘developmental origins of disease’ phenomenon is a maladaptive consequence of an ancestral mechanism of developmental plasticity that may have had adaptive value in the evolution of generalist species such as Homo sapiens. BioEssays 29: 145–154, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Genomic imprinting is an epigenetic marking process that confers parent‐of‐origin‐dependent expression on certain genes. These imprinted genes are sometimes found in clusters, suggesting a possible involvement of higher order regulatory elements controlling expression and imprinting of genes organised in such clusters. In the distal chromosome 7 there are at least four imprinted genes: Mash2, Ins2, Igf2 and H19. Recent evidence(1) suggests that imprinting and expression of at least Igf2 and H19 may be mechanistically linked.

In lieu of an abstract, here is a brief excerpt of the content:Reviewed by:The Maternal Imprint: The Contested Science of Maternal-Fetal Effects (2021) by Sarah RichardsonQuill KuklaQuill Kukla, review of Sarah Richardson's The Maternal Imprint: The Contested Science of Maternal-Fetal Effects (2021)I had been eagerly anticipating the release of Sarah Richardson's meticulously researched The Maternal Imprint: The Contested Science of Maternal-Fetal Effects (2021) for several years, and I was not disappointed. A leading feminist scholar of the history and philosophy of (...) science, Richardson traces the scientific history of the idea that pregnant people's bodies control the future health, character, and well-being of their offspring. She also explores how this science is translated into social messaging and shaped by social ideology. Richardson delves into the details of the methodology, motivations, results, and communication of the science of maternal influences. She reveals a history of shaky results, contested methods, and socially loaded messaging, unified by a sustained interest in framing maternal bodies as sites of risk and responsibility for birth outcomes.A central narrative of the book is that the perceived location and mechanism through which pregnant bodies control fetal development keeps shifting around; over time, scientists have located this maternal influence in the uterine environment, the cytoplasm, the methylation of DNA, maternal nutrition, and even in the emotions, thoughts, and imagination of the mother, among other locations.1 Each time a version of the maternal influence hypothesis re-emerges, targeting a different bodily location and mechanism, it comes along with similar social messaging: pregnant people are distinctively responsible for the 'quality' of their children; their bodies are distinctive sites of risk, in need of social management; and their influence can be understood and controlled independent of the context in which they live. Given how many times this scientific hypothesis and its accompanying social messaging has died and been reborn, it is hard not to conclude, with Richardson, that background ideology compels us to keep searching for new stories that take this same form. The idea that pregnant people's bodies are understood as decontextualized and heightened sites of risk and responsibility for birth outcomes, in need of systematic discipline (both self-discipline and social discipline) in order to ensure their production of proper offspring, is one that has been explored [End Page e-1] in quite a bit of depth within feminist theory and reproductive ethics over the last thirty years. To name just a few, Barbara Duden's Disembodying Women: Perspectives on Pregnancy and the Unborn (1993), Deborah Lupton's "Risk and the Ontology of Pregnant Embodiment" (1999), Lisa Mitchell's Baby's First Picture: Ultrasound and the Politics of Fetal Subjects (2001), and my own Mass Hysteria: Medicine, Culture, and Mothers' Bodies (2005) are all works firmly within this tradition. What is new about Richardson's book is not the development and exploration of this cultural narrative and imaginary, but rather her rigorous and skillful analysis of the science that has grown out of and undergirded it. Richardson is a masterful writer, who makes scientific details comprehensible and fascinating. Her historical and epistemological analyses of exactly what shaped the science at each stage, what each scientific iteration did and didn't manage to show, and how these different scientific movements were translated into public messaging, is sharp and compelling. Richardson shows us the inner workings of how scientific programs build momentum; how scientists make methodological decisions; and how results feed into ongoing research programs. From this book, we also develop a rich sense of just how much uncertainty is baked into the science of human development, and how both scientific and public excitement about a given research program are mostly independent of the success and security of the science that comes out of it. The book traces 150 years of the history of the science of maternal influences, culminating in the current focus on epigenetics—which, like various past maternal influence theories, has ignited our broader social imagination. Epigenetics, roughly, is the study of molecular changes outside our DNA that control how genes express themselves. Environmental stimuli (such as stress) can cause changes in methylation, and thereby influence the expression of the genome: "Epigenetic markers that help determine whether a... (shrink)

Although female and male gametes are presumably equivalent in their genetic contribution to embryos, they carry specific information, perhaps reversibly imprinted into the genomes during oogenesis and spermatogenesis, as to their maternal or paternal origin. This information is crucial for embryogenesis and, in the absence of at least one haploid set of chromosomes from each parent, embryos do not develop to term. The paternal genome is probably required for proliferation of extraembryonic tissues and the maternal genome for some stages of (...) embryogeneis. Furthermore, the effects of certain mutations are determined by the paternal or maternal origin of the inheritance. (shrink)

Autistic-spectrum conditions and psychotic-spectrum conditions (mainly schizophrenia, bipolar disorder, and major depression) represent two major suites of disorders of human cognition, affect, and behavior that involve altered development and function of the social brain. We describe evidence that a large set of phenotypic traits exhibit diametrically opposite phenotypes in autistic-spectrum versus psychotic-spectrum conditions, with a focus on schizophrenia. This suite of traits is inter-correlated, in that autism involves a general pattern of constrained overgrowth, whereas schizophrenia involves undergrowth. These disorders also (...) exhibit diametric patterns for traits related to social brain development, including aspects of gaze, agency, social cognition, local versus global processing, language, and behavior. Social cognition is thus underdeveloped in autistic-spectrum conditions and hyper-developed on the psychotic spectrum.;>We propose and evaluate a novel hypothesis that may help to explain these diametric phenotypes: that the development of these two sets of conditions is mediated in part by alterations of genomic imprinting. Evidence regarding the genetic, physiological, neurological, and psychological underpinnings of psychotic-spectrum conditions supports the hypothesis that the etiologies of these conditions involve biases towards increased relative effects from imprinted genes with maternal expression, which engender a general pattern of undergrowth. By contrast, autistic-spectrum conditions appear to involve increased relative bias towards effects of paternally expressed genes, which mediate overgrowth. This hypothesis provides a simple yet comprehensive theory, grounded in evolutionary biology and genetics, for understanding the causes and phenotypes of autistic-spectrum and psychotic-spectrum conditions. (shrink)

Parts of the genome of a single individual can have conflicting interests, depending on which parent they were inherited from. One mechanism by which these conflicts are expressed in some taxa, including mammals, is genomic imprinting, which modulates the level of expression of some genes depending on their parent of origin. Imprinted gene expression is known to affect body size, brain size, and the relative development of various tissues in mammals. A high fraction of imprinted gene expression occurs (...) in the brain. Biologists including Hamilton, Trivers and Haig have proposed that this may explain some intrapersonal conflict in humans. This speculation amounts to an inference from conflict within the genome to conflict within the brain or mind. This is a provocative proposal, which deserves serious attention. In this paper I assess aspects of Haig’s version of the proposal. I argue, first, that the notion that intragenomic conflict predicts personal inconsistency should be rejected. Second, while it is unlikely that it credibly predicts sub-personal agents representing conflicting genetic interests, it is plausible that it predicts that the division of cognitive labour could be exploited to turn sub-systems into proxies for conflicting interests. (shrink)

Organisms can be treated as optimizers when there is consensus among their genes about what is best to be done, but genomic consensus is often lacking, especially in interactions among kin because kin share some genes but not others. Grafen adopts a majoritarian perspective in which an individual’s interests are identified with the interests of the largest coreplicon of its genome, but genomic imprinting and recombination factionalize the genome so that no faction may predominate in some interactions (...) among kin. Once intragenomic conflicts are recognized, the individual organism can be conceptualized as an arbiter among competing interests within a collective. Organismal adaptation can be recognized without phenotypes being optimized. (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)

We hypothesize that rapid eye movement or REM sleep evolved, in part, to mediate sexual/reproductive behaviors and strategies. Because development of sexual and mating strategies depends crucially on early attachment experiences, we further hypothesize that REM functions to mediate attachment processes early in life. Evidence for these hypotheses comes from (1) the correlation of REM variables with both attachment and sexual/reproductive variables; (2) attachment-related and sex-related hormonal release during REM; (3) selective activation during REM of brain sites implicated in attachment (...) and sexual processes; (4) effects of maternal deprivation on REM; (5) effects of REM deprivation on sexual behaviors; and (6) the REM-associated sexual excitation. To explain why we find associations among REM sleep, attachment, and adult reproductive strategies, we rely on recent extensions of parent-offspring conflict theory. Using data from recent findings on genomic imprinting, Haig (2000) and others suggest that paternally expressed genes are selected to promote growth of the developing fetus/child at the expense of the mother, while maternally expressed genes counter these effects. Because developmental REM facilitates attachment-related outcomes in the child, developmental REM may be regulated by paternally expressed genes. In that case, REM may have evolved to support the “aims” of paternal genes at the expense of maternal genes. (shrink)

Monoallelic gene expression has played a significant role in the evolution of mammals enabling the expansion of a vast repertoire of olfactory receptor types and providing increased sensitivity and diversity. Monoallelic expression of immune receptor genes has also increased diversity for antigen recognition, while the same mechanism that marks a single allele for preferential rearrangement also provides a distinguishing feature for directing hypermutations. Random monoallelic expression of the X chromosome is necessary to balance gene dosage across sexes. In marsupials only (...) the maternal X chromosome is expressed, while in eutherian mammals the paternal X genes are silenced in the developing placenta and early blastocyst. These examples of epigenetic gene regulation commonly employ asynchrony of replication, the binding of polycomb proteins and antisense RNA, and histone modifications to chromatin structure. The same is true for genomic imprinting which among vertebrates is unique to mammals and represents a special kind of epigenetic modification that is heritable according to parent of origin. Genomic imprinting pervades many aspects of mammalian growth and evolution but in particular has played a significant role in the co‐adaptive evolution of the mother and foetus. (shrink)

DNA methylation plays a role in the repression of gene expression in animal cells. In the mouse preimplantation embryo, most genes are unmethylated but a wave of de novo methylation prior to gastrulation generates a bimodal pattern characterized by unmethylated CpG island‐containing housekeeping genes and fully modified tissue‐specific genes. Demethylaton of individual genes then takes place during cell type specific differentiation, and this demodification may be a required step in the process of transcriptional activation. DNA modification is also involved in (...) the maintenance of gene repression on the inactive X chromosome in female somatic cells and the marking of parental alleles at genomically imprinted gene loci. (shrink)

Social circumstances often impinge on later generations in a socio-economic manner, giving children an uneven start in life. Overfeeding and overeating might not be an exception. The pathways might be complex but one direct mechanism could be genomic imprinting and loss of imprinting. An intergenerational "feedforward" control loop has been proposed, that links grandparental nutrition with the grandchild's growth. The mechanism has been speculated to be a specific response, e.g. to their nutritional state, directly modifying the setting (...) of the gametic imprint on one or more genes. This study raises the question: Can overnutrition during a child's slow growth period trigger such direct mechanisms and partly determine mortality?Data were collected by following-up a cohort born in 1905 in Överkalix parish, northernmost Sweden. The probands were characterised by their parents' or grandparents' access to food during their own slow growth period. Availability of food in the area was defined by referring to historical data on harvests and food prices, records of local community meetings and general historical facts. (shrink)

Debates over adaptationism can be clarified and partially resolved by careful consideration of the ‘grain’ at which evolutionary processes are described. The framework of ‘adaptive landscapes’ can be used to illustrate and facilitate this investigation. We argue that natural selection may have special status at an intermediate grain of analysis of evolutionary processes. The cases of sickle-cell disease and genomic imprinting are used as case studies.

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)

Crespi & Badcock (C&B) present an appealing and parsimonious synthesis arguing that schizophrenia and autism are differentially regulated by maternal versus paternal genomic imprinting, respectively. We argue that animal models related to schizophrenia and autism provide a useful platform to explore the mechanisms outlined by C&B. We also note that schizophrenia and autism share certain risk factors such as advanced paternal age. Apart from genomic imprinting, copy number variants related to advanced paternal age may also contribute (...) to the differential trajectory of brain development associated with autism and schizophrenia. (shrink)

Sexual reproduction is almost ubiquitous among multicellular organisms even though it entails severe fitness costs. To resolve this apparent paradox, an extensive body of research has been devoted to identifying the selective advantages of recombination that counteract these costs. Yet, how easy is it to make the transition to asexual reproduction once sexual reproduction has been established for a long time? The present review approaches this question by considering factors that impede the evolution of parthenogenesis in animals. Most importantly, eggs (...) need a diploid chromosome set in most species in order to develop normally. Next, eggs may need to be activated by sperm, and sperm may also contribute centrioles and other paternal factors to the zygote. Depending on how diploidy is achieved mechanistically, further problems may arise in offspring that stem from ‘inbreeding depression’ or inappropriate sex determination systems. Finally, genomic imprinting is another well-known barrier to the evolution of asexuality in mammals. Studies on species with occasional, deficient parthenogenesis indicate that the relative importance of these constraints may vary widely. The intimate evolutionary relations between haplodiploidy and parthenogenesis as well as implications for the clade selection hypothesis of the maintenance of sexual reproduction are also discussed. (shrink)

I propose that the underlying adaptation enabling the reproductive strategy of birthing live young (viviparity) is retraction of the site of fertilization within the female reproductive tract, and that this evolved as a means of postcopulatory sexual selection. There are three conspicuous aspects associated with viviparity: (i) internal development is a complex trait often accompanied by a suite of secondary adaptations, yet it is unclear how the intermediate state of this trait – egg retention – could have evolved; (ii) viviparity (...) often results in a reduction in fecundity; (iii) viviparity has evolved independently many times across a diverse array of animal groups. Focusing on the Diptera (true flies), I provide explanations for these observations. I further propose that fecundity is not traded‐off to enable potential benefits of viviparity, but rather that loss of fecundity is directly selected and egg retention is an indirect consequence – a model that provides a unifying common basis for the ubiquity of viviparity. (shrink)

Literature on maternal exposures and the risk of epigenetic changes or diseases in the offspring is growing. Paternal contributions are often not considered. However, some animal and epidemiologic studies on various contaminants, nutrition, and lifestyle‐related conditions suggest a paternal influence on the offspring's future health. The phenotypic outcomes may have been attributed to DNA damage or mutations, but increasing evidence shows that the inheritance of environmentally induced functional changes of the genome, and related disorders, are (also) driven by epigenetic components. (...) In this essay we suggest the existence of epigenetic windows of susceptibility to environmental insults during sperm development. Changes in DNA methylation, histone modification, and non‐coding RNAs are viable mechanistic candidates for a non‐genetic transfer of paternal environmental information, from maturing germ cell to zygote. Inclusion of paternal factors in future research will ultimately improve the understanding of transgenerational epigenetic plasticity and health‐related effects in future generations. (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)

The imprints left by quantum mechanics in classical (Hamiltonian) mechanics are much more numerous than is usually believed. We show that the Schrödinger equation for a nonrelativistic spinless particle is a classical equation which is equivalent to Hamilton’s equations. Our discussion is quite general, and incorporates time-dependent systems. This gives us the opportunity of discussing the group of Hamiltonian canonical transformations which is a non-linear variant of the usual symplectic group.

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)

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)

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)

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)

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)

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)