A network of gene regulation organized in a hierarchical and combinatorial manner is crucially involved in the development of the neural network, and has to be considered one of the main substrates of genetic change in its evolution. Though qualitative features may emerge by way of the accumulation of rather unspecific quantitative changes, it is reasonable to assume that at least in some cases specific combinations of regulatory parts of the genome initiated new directions of evolution, (...) leading to novel capabilities of the brain. These notions are applied, in this paper, to the evolution of the capability of cognition-based human empa­thy. It is suggested that it has evolved as a secondary effect of the evolution of strategic thought. Development of strategies depends on abstract representations of one’s own pos­sible future states in one’s own brain to allow assessment of their emotional desirability, but also on the representation and emotional evaluation of possible states of others, allowing anticipation of their behaviour. This is best achieved if representations of others are con­nected to one’s own emotional centres in a manner similar to self-representations. For this reason, the evolution of the human brain is assumed to have established representations with such linkages. No group selection is involved, because the quality of strategic thought affects the fitness of the individual. A secondary effect of this linkage is that both the actual states and the future perspectives of others elicit vicarious emotions, which may contribute to the motivations of altruistic behaviour. (shrink)

A discussion of plasticity genes and the genetic architecture of gene-environment interactions.

Understanding the operation and evolution of gene regulation networks is critical to understanding ontogeny and evolution. According to Stuart Kauffman's view, (1) each cell type cycles through its own repeated pattern of gene expression, (2) the order of ontogeny is dependent on these cycles being short, and (3) evolution is possible because these cycles mutate gradually. This view of gene regulation reflects Kauffman's view that ontogeny is fundamentally the process of cells repeating (...) cycles of activity. I criticize Kauffman's view of gene regulation networks and offer the connectionist theory of gene regulation as an alternative. On this view, the generic order of gene regulation mechanisms is due to the qualitatively consistent way that one gene product influences the expression of another. This allows networks to be stable and evolve to regulate accurately, allowing cells to react appropriately to their microenvironments, due to design by natural selection. 1. Introduction2. Kauffman's Model of Gene Regulation3. Explaining the Order of Kauffman's K = 2 Networks4. The Importance and Relevance of Kauffman's Explanations of the Order of Gene Regulation5. Additional Orderly Facts of Transcription6. The Order of Network Accuracy7. The Accuracy of Connectionist Networks8. The Evolvability of Gene Regulation Networks9. Laws of Structure. (shrink)

Plant MADS‐box genes encode transcriptional regulators that are critical for a number of developmental processes. In the angiosperms (the flowering plants), these include the specification of floral organ identities, flowering time and fruit development. It appears that the MADS box gene family has undergone considerable gene duplication and sequence divergence within the angiosperms. Here I discuss the possibility that these events have allowed the recruitment of these genes to new developmental pathways in particular angiosperm lineages. Recent analyses of (...) sequence changes, expression patterns and, in a few cases, gene function are beginning to provide tantalizing evidence for deciphering when and how such genetic diversification has led to particular morphological innovations. In the future, comparative studies of large numbers of species will be required to assess the extent of such variation as well as to fully understand the mechanisms by which evolution of these developmental regulators has played a role in shaping new morphologies. BioEssays 25:637–646, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Evolution has shaped all living organisms on Earth, although many details of this process are shrouded in time. However, it is possible to see, with one's own eyes, evolution as it happens by performing experiments in defined laboratory conditions with microbes that have suitably fast generations. The longest‐running microbial evolution experiment was started in 1988, at which time twelve populations were founded by the same strain ofEscherichia coli. Since then, the populations have been serially propagated and have (...) evolved for tens of thousands of generations in the same environment. The populations show numerous parallel phenotypic changes, and such parallelism is a hallmark of adaptive evolution. Many genetic targets of natural selection have been identified, revealing a high level of genetic parallelism as well. Beneficial mutations affect all levels of gene regulation in the cells including individual genes and operons all the way to global regulatory networks. Of particular interest, two highly interconnected networks—governing DNA superhelicity and the stringent response—have been demonstrated to be deeply involved in the phenotypic and genetic adaptation of these experimental populations. BioEssays 29:846–860, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

The Segregation Distorter (SD) system of Drosophila melanogaster is one the best‐characterized meiotic drive complexes known. SD gains an unfair transmission advantage through heterozygous SD/SD+ males by incapacitating SD+‐bearing spermatids so that virtually all progeny inherit SD. Segregation distorter (Sd), the primary distorting locus in the SD complex, is a truncated duplication of the RanGAP gene, a major regulator of the small GTPase Ran, which has several functions including the maintenance of the nucleocytoplasmic RanGTP concentration gradient that mediates nuclear (...) transport. The truncated Sd‐RanGAP protein is enzymatically active but mislocalizes to the nucleus where it somehow causes distortion. Here I present data consistent with the idea that wild‐type RanGAP, and possibly other loci able to influence the RanGTP gradient, has been caught up in an ancient genetic conflict that predates the SD complex. The legacy of this conflict could include the unexpectedly rapid evolution of nuclear transport‐related proteins, the accumulation of chromosomal inversions, the recruitment of gene duplications, and the turnover of repetitive sequences in the centric heterochromatin. BioEssays 29:386–391, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

It has long been thought that gene expression is tightly regulated in multicellular eukaryotes, so that expression profiles match functional profiles. This conception emerged from the assumption that gene activity is synonymous with gene function. This paradigm was first challenged by comparative protein electrophoresis studies showing extensive differences in expression patterns among related species. The paradigm is now being challenged by evolutionary transcriptomics using microarray technologies. Most gene expression profiles display features that lack any obvious functional (...) significance. The so‐called “ectopic” expression refers to the expression of genes at times and locations where the target gene is not known to have a function. However, ectopic expression might be associated with genuine function even if this function is not essential or has yet to be ascertained. Alternatively, ectopic expression might come about as a superfluous by‐product of regulatory systems, which would call for a revision of prevailing ideas about the specificity of gene regulation. We herein review available evidence for ectopic expression and the hypotheses proposed for its origin and evolution. We propose that ectopic expression must be regarded as part of an integrated phenotypic whole. It seems likely that ectopic expression represents a leak in the evolution of regulatory systems, but one that is endowed with considerable evolutionary possibilities. BioEssays 27:592–601, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

Alternative splicing (AS) is a widespread mechanism with an important role in increasing transcriptome and proteome diversity by generating multiple different products from the same gene. Evolutionary studies of AS have focused primarily on the conservation of alternatively spliced sequences or of the AS pattern of those sequences itself. Less is known about the evolution of the regulation of AS, but several studies, working from different perspectives, have recently made significant progress. Here, we categorize the different levels (...) of AS evolution, and summarize the studies on evolution of AS regulation, which point to a high level of evolutionary conservation of the regulation of AS events conserved between related species. This suggests that the quantitative regulation of AS is an intrinsic part of AS function. We discuss the potential role of changes in developmental regulation of AS as an additional layer in complex gene regulatory networks and in the emergence of genetic novelties. (shrink)

Day length provides an important environmental cue by signalling conditions favourable for flowering. While Arabidopsis promotes flowering in response to long days, rice promotes flowering in response to short days. Despite this difference, a recent paper reveals that the network controlling this response is highly conserved in these distantly related plants, only the activity of one component is reversed.1 This reveals how an important developmental process can be diversified for adaptation by using the same set of genes, but regulating them (...) differently. BioEssays 25:829–832, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

It is presumed that the evolution of morphological diversity in animals and plants is driven by changes in the developmental processes that govern morphology, hence basically by changes in the function and/or expression of a defined set of genes that control these processes. A large body of evidence has suggested that changes in developmental gene regulation are the predominant mechanisms that sustain morphological evolution, being much more important than the evolution of the primary sequences and (...) functions of proteins. Recent reports1, 2 challenge this idea by highlighting functional evolution of Hox proteins during the evolutionary history of arthropods. BioEssays 24:775–779, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

Presented in six principal analytic chapters with supporting appendices, this book explores the role of Islam in precipitating Europe's twelfth century commercial renaissance. Employing the classic analytic techniques of economics, Gene Heck determines that medieval Europe's feudal interregnum was largely caused by indigenous governmental business regulation and not by shifts in international trade patterns. He then proceeds by demonstrating how Islamic economic precepts provided the ideological rationales that empowered medieval Europe to escape its three-centuries-long experiment in "Dark Age (...) economics" ― in the process, providing the West with its archetypic tools of capitalism. While treatises such as Maxime Rodinson's excellent book, Islam and Capitalism, document the capitalistic nature of the Islamic economic system, in applying modern economic method to medieval orientalist historiography, this work is unique in capturing both the evolution and the impact of the system's role in forging medieval history. (shrink)

Alternative splicing (AS) is a widespread mechanism with an important role in increasing transcriptome and proteome diversity by generating multiple different products from the same gene. Evolutionary studies of AS have focused primarily on the conservation of alternatively spliced sequences or of the AS pattern of those sequences itself. Less is known about the evolution of the regulation of AS, but several studies, working from different perspectives, have recently made significant progress. Here, we categorize the different levels (...) of AS evolution, and summarize the studies on evolution of AS regulation, which point to a high level of evolutionary conservation of the regulation of AS events conserved between related species. This suggests that the quantitative regulation of AS is an intrinsic part of AS function. We discuss the potential role of changes in developmental regulation of AS as an additional layer in complex gene regulatory networks and in the emergence of genetic novelties. (shrink)

Novel regulatory elements that enabled expression of pre‐existing immune genes in reproductive tissues and novel immune genes with pregnancy‐specific roles in eutherians have shaped the evolution of mammalian pregnancy by facilitating the emergence of novel mechanisms for immune regulation over its course. Trade‐offs arising from conflicting fitness effects on reproduction and host defenses have further influenced the patterns of genetic variation of these genes. These three mechanisms (novel regulatory elements, novel immune genes, and trade‐offs) played a pivotal role (...) in refining the regulation of maternal immune systems during pregnancy in eutherians, likely facilitating the establishment of prolonged direct maternal–fetal contact in eutherians without causing immunological rejection of the genetically distinct fetus. (shrink)

This chapter contains sections titled: The Evolution of the Institutions of Science The Big Business of Biotech, and the Cornucopia of the HGP The Marketplace of Genes Open Source and Free Markets Open Source in Biology National Regulation of Gene Markets DNA Wants to be Free.

.Evolutionary analysis focuses on how genes build organisms with different strategies for engaging and solving life’s challenges of survival and reproduction. One of those challenges is competing with conspecifics for limited resources including reproductive opportunities. This article will suggest that there is now good evidence for considering two dimensions of social competition. First, we will label antisocial strategies, to the extent that they tend to be self-focused, threat sensitive and aggressive, as well as using tactics of bulling, threatening, intimidating or (...) even injuring/killing competitors. Their strategic goal is to stimulate fear-inhibition, flight or submissive compliance in subordinates. Such strategies turn off and inhibit care and affiliative social interactions and motivation and they can be enacted by parents, teachers and leaders. The social signals emitted stimulate various aspects of threat processing in recipients, create stressful and highly stratified groups with a range of detrimental psychological and physiological effects. Second, in contrast, prosocial strategies seek to create relaxed and secure social interactions that enable sharing, cooperative and mutually supportive and beneficial relationships. The friendly and low/no threat social signals emitted in friendly cooperative and affiliative relationships stimulate physiological systems (e.g., oxytocin, the vagus parasympathetic system) that down regulates threat processing, enhances the immune system, facilitates frontal cortical processes and general wellbeing. This article reviews the literature pertaining to the evidence for these two dimensions of social engagement. (shrink)

Short (“seed”) or extended base pairing between microRNAs (miRNAs) and their target RNAs enables post‐transcriptional silencing in many organisms. These interactions allow the computational prediction of potential targets. In model organisms, predicted targets are frequently validated experimentally; hence meaningful miRNA‐regulated processes are reported. However, in non‐models, these reports mostly rely on computational prediction alone. Many times, further bioinformatic analyses such as Gene Ontology (GO) enrichment are based on these in silico projections. Here such approaches are reviewed, their caveats are (...) highlighted and the ease of picking false targets from predicted lists is demonstrated. Discoveries that shed new light on how miRNAs evolved to regulate targets in various phyletic groups are discussed, in addition to the pitfalls of target identification in non‐model organisms. The goal is to prevent the misuse of bioinformatic tools, as they cannot bypass the biological understanding of miRNA–target regulation. (shrink)

The gelsolin gene family encodes a number of higher eukaryotic actin-binding proteins that are thought to function in the cytoplasm by severing, capping, nucleating or bundling actin filaments. Recent evidence, however, suggests that several members of the gelsolin family may have adopted unexpected nuclear functions including a role in regulating transcription. In particular, flightless I, supervillin and gelsolin itself have roles as coactivators for nuclear receptors, despite the fact that their divergence appears to predate the evolutionary appearance of nuclear (...) receptors. Flightless I has been shown to bind both actin and the actin-related BAF53a protein, which are subunits of SWI/SNF-like chromatin remodelling complexes. The primary sequences of some actin-related proteins such as BAF53a exhibit conservation of residues that, in actin itself, are known to interact with gelsolin-related proteins. In summary, there is a growing body of evidence supporting a biological role in the nucleus for actin, Arps and actin-binding proteins and, in particular, the gelsolin family of actin-binding proteins. (c) 2005 Wiley Periodicals, Inc. (shrink)

The eukaryotic nucleosome, the basic unit of chromatin, is thermodynamically stable and plays critical roles in the cell, including the maintenance of DNA topology and regulation of gene expression. At its C2 axis of symmetry, the nucleosome exhibits a domain that can coordinate divalent metal ions. This article discusses the roles of the metal‐binding domain in the nucleosome structure, function, and evolution.

Here I present and discuss a model that, among other things, appears able to describe the dynamics of cancer cell origin from the perspective of stable and unstable gene expression profiles. In identifying suchaberrantgene expression profiles as lying outside the normal stable states attracted through development and normal cell differentiation, the hypothesis explains why cancer cells accumulate mutations, to which they are not robust, and why these mutations create a new stable state far from the normal gene expression (...) profile space. Such cells are in strong contrast with normal cell types that appeared as an attractor state in the gene expression dynamical system under cell‐cell interaction and achieved robustness to noise through evolution, which in turn also conferred robustness to mutation. In complex gene regulation networks, otheraberrantcellular states lacking such high robustness are expected to remain, which would correspond to cancer cells. (shrink)

The internal organs of all vertebrates are asymmetrically organised across the left–right axis. The development of this asymmetry is controlled by a molecular pathway that includes the signalling molecule Nodal and the transcription factor Pitx2, proteins encoded by genes that are predominantly expressed on the left side of all vertebrate embryos studied to date. Vertebrates share Phylum Chordata with two other groups of animals, amphioxus and the urochordates (including ascidians). Both these taxa develop left–right asymmetries, and recent studies have begun (...) to address the degree of conservation of nodal and Pitx2 in this process. Pitx2 is a member of the Pitx homeobox gene family, and in both amphioxus and ascidians Pitx gene expression is predominantly left sided. These studies suggest that left–right asymmetry in all chordates is regulated by a conserved developmental pathway, and that this pathway evolved before the separation of the lineages leading to living chordates. BioEssays 24:1004–1011, 2002. © 2002 Wiley‐Periodicals, Inc. (shrink)

The use of socially learned information (culture) is central to human adaptations. We investigate the hypothesis that the process of cultural evolution has played an active, leading role in the evolution of genes. Culture normally evolves more rapidly than genes, creating novel environments that expose genes to new selective pressures. Many human genes that have been shown to be under recent or current selection are changing as a result of new environments created by cultural innovations. Some changed in (...) response to the development of agricultural subsistence systems in the Early and Middle Holocene. Alleles coding for adaptations to diets rich in plant starch (e.g., amylase copy number) and to epidemic diseases evolved as human populations expanded (e.g., sickle cell and G6PD defi- ciency alleles that provide protection against malaria). Large-scale scans using patterns of linkage disequilibrium to detect recent selection suggest that many more genes evolved in response to agriculture. Genetic change in response to the novel social environment of contemporary modern societies is also likely to be occurring. The functional effects of most of the alleles under selection during the last 10,000 years are currently unknown. Also unknown is the role of paleoenvironmental change in regulating the tempo of hominin evolution. Although the full extent of culture-driven gene-culture coevolution is thus far unknown for the deeper history of the human lineage, theory and some evidence suggest that such effects were profound. Genomic methods promise to have a major impact on our understanding of gene-culture coevolution over the span of hominin evolutionary history. (shrink)

This paper argues that the “long 1970s” (1969–1983) is an important though often overlooked period in the development of a rich landscape in the research of metabolism, development, and evolution. The period is marked by: shrinking public funding of basic science, shifting research agendas in molecular biology, the incorporation of new phenomena and experimental tools from previous biological research at the molecular level, and the development of recombinant DNA techniques. Research was reoriented towards eukaryotic cells and development, and in (...) particular towards “giant” RNA processing and transcription. We will here focus on three different models of developmental regulation published in that period: the two models of eukaryotic genetic regulation at the transcriptional level that were developed by Georgii P. Georgiev on the one hand, and by Roy Britten and Eric Davidson on the other; and the model of genetic sufficiency and evolution of regulatory genes proposed by Emile Zuckerkandl. These three cases illustrate the range of exploratory hypotheses that characterised the challenging landscape of gene regulation in the 1970s, a period that in hindsight can be labelled as transitional, between the biology at the laboratory bench of the preceding period, and the biology of genetic engineering and intensive data-driven research that followed. (shrink)

Bacterial resistance mechanisms to the antibiotics known as β‐lactams, which include the penicillins and cephalosporins, can take several forms but frequently involve the production of β‐lactamases from either plasmid‐ or chromosomally‐encoded loci. Gram negative bacteria express a β‐lactamase from evolutionarily related chromosomal ampC genes. Genetic analysis of both inducible and constitutively expressed AmpC β‐lactamases provide insights into the mechanisms regulating production of the enzyme. Evolutionary relationships between the genes of different species are discussed, as well as the regulatory mechanisms that (...) in both laboratory mutants and clinical isolates lead to overproduction of β‐lactamase. (shrink)

The genomes of vertebrates, flies, and nematodes contain highly conserved noncoding elements (CNEs). CNEs cluster around genes that regulate development, and where tested, they can act as transcriptional enhancers. Within an animal group CNEs are the most conserved sequences but between groups they are normally diverged beyond recognition. Alternative CNEs are, however, associated with an overlapping set of genes that control development in all animals. Here, we discuss the evidence that CNEs are part of the core gene regulatory networks (...) (GRNs) that specify alternative animal body plans. The major animal groups arose >550 million years ago. We propose that the cis‐regulatory inputs identified by CNEs arose during the “re‐wiring” of regulatory interactions that occurred during early animal evolution. Consequently, different animal groups, with different core GRNs, contain alternative sets of CNEs. Due to the subsequent stability of animal body plans, these core regulatory sequences have been evolving in parallel under strong purifying selection in different animal groups. (shrink)

The role of gene expression in evolutionary adaptation has been a subject of debate for over 40 years.cis‐regulation of transcription has been proposed to be the primary source of morphological novelty in evolution, though this is based on only a handful of examples. Recently the first genome‐wide studies of gene expression adaptation have been published, giving us an initial global view of this process. Systematic studies such as these will allow a number of key questions currently (...) facing the field of gene expression evolution to be addressed. (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)

A gene's “expression profile” denotes the number of transcripts present relative to all other transcripts. The overall rate of transcript production is determined by transcription and RNA processing rates. While the speed of elongating RNA polymerase II has been characterized for many different genes and organisms, gene‐architectural features – primarily the number and length of exons and introns – have recently emerged as important regulatory players. Several new studies indicate that rapidly cycling cells constrain gene‐architecture toward short (...) genes with a few introns, allowing efficient expression during short cell cycles. In contrast, longer genes with long introns exhibit delayed expression, which can serve as timing mechanisms for patterning processes. These findings indicate that cell cycle constraints drive the evolution of gene‐architecture and shape the transcriptome of a given cell type. Furthermore, a tendency for short genes to be evolutionarily young hints at links between cellular constraints and the evolution of animal ontogeny. (shrink)

Biological evolution and technological innovation, while differing in many respects, also share common features. In particular, implementation of a new technology in the market is analogous to the spreading of a new genetic trait in a population. Technological innovation may occur either through the accumulation of quantitative changes, as in the development of the ocean clipper, or it may be initiated by a new combination of features or subsystems, as in the case of steamships. Other examples of the latter (...) type are electric networks that combine the generation, distribution, and use of electricity, and containerized transportation that combines standardized containers, logistics, and ships. Biological evolution proceeds, phenotypically, in many small steps, but at the genetic level novel features may arise not only through the accumulation of many small, common mutational changes, but also when distinct, relatively rare genetic changes are followed by many further mutations. In particular, capabilities of biologically modern man may have been initiated, perhaps some 150 000 years ago, by one or few accidental but distinct combinations of modules and subroutines of gene regulation which are involved in the generation of the neural network in the cerebral cortex. It is even conceivable that it was one primary genetic event that initiated the evolution of biologically modern man, introducing some novel but subtle feature of connectivity into the cerebral cortex which allowed for meta-levels of abstraction and upgraded modes of information processing. This may have set the stage for the evolution of integrated but diverse higher capabilities such as structured language, symbolic thought, strategic thought, and cognition based empathy. (shrink)

Transposable elements are no longer considered to be “junk” DNA. Here, we review how TEs can impact gene regulation systematically. TEs encode various regulatory elements that enables them to regulate gene expression. RJ Britten and EH Davidson hypothesized that TEs can integrate the function of various transcriptional regulators into gene regulatory networks. Uniquely TEs can deposit regulatory sites across the genome when they transpose, and thereby bring multiple genes under control of the same regulatory logic. Several (...) studies together have robustly established that TEs participate in embryonic development and oncogenesis. We discuss the regulatory characteristics of TEs in context of evolution to understand the extent of their impact on gene networks. Understanding these features of TEs is central to future investigations of TEs in cellular processes and phenotypic presentations, which are applicable to development and disease studies. We re-visit the Britten–Davidson “gene-battery” model and understand the genetic and transcriptional impact of TEs in innovating gene regulatory networks. Transposable elements are exogenous sequences that have either been co-opted or repurposed for host functions. The vast amounts of TE sequence in the genome provides raw material for gene expression regulation, and still remains to be fully understood; the “gene-battery” model provides the basis for understanding this. (shrink)

A study is made of some aspects of parallel evolution in Chelicerata. Definitions are given of parallel evolution, convergence, homology and analogy. It is pointed out that the concept of parallel evolution (parallelism) is initially formed in an empirical way, and that a judgment must be based on formal criteria. Particular attention is paid to the rôle of gene regulation in parallel evolution, to the special case of convergence as a result of heterologous regulatory (...) mechanisms, to parallel evolution in homonomous structures (and the superposition of parallelisms and divergences), and to parallelism in the evolution of characters used in higher classification. (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)

Protein post‐translational modifications (PTMs) play a crucial role in all cellular functions by regulating protein activity, interactions and half‐life. Despite the enormous diversity of modifications, various PTM systems show parallels in their chemical and catalytic underpinnings. Here, focussing on modifications that involve the addition of new elements to amino‐acid sidechains, I describe historical milestones and fundamental concepts that support the current understanding of PTMs. The historical survey covers selected key research programmes, including the study of protein phosphorylation as a regulatory (...) switch, protein ubiquitylation as a degradation signal and histone modifications as a functional code. The contribution of crucial techniques for studying PTMs is also discussed. The central part of the essay explores shared chemical principles and catalytic strategies observed across diverse PTM systems, together with mechanisms of substrate selection, the reversibility of PTMs by erasers and the recognition of PTMs by reader domains. Similarities in the basic chemical mechanism are highlighted and their implications are discussed. The final part is dedicated to the evolutionary trajectories of PTM systems, beginning with their possible emergence in the context of rivalry in the prokaryotic world. Together, the essay provides a unified perspective on the diverse world of major protein modifications. (shrink)

The pathway that controls sexual fate in the nematode Caenorhabditis elegans has been well characterized at the molecular level. By identifying differences between the sex‐determination mechanisms in C. elegans and other nematode species, it should be possible to understand how complex sex‐determining pathways evolve. Towards this goal, orthologues of many of the C. elegans sex regulators have been isolated from other members of the genus Caenorhabditis. Rapid sequence evolution is observed in every case, but several of the orthologues appear (...) to have conserved sex‐determining roles. Thus extensive sequence divergence does not necessarily coincide with changes in pathway structure, although the same forces may contribute to both. This review summarizes recent findings and, with reference to results from other animals, offers explanations for why sex‐determining genes and pathways appear to be evolving rapidly. Experimental strategies that hold promise for illuminating pathway differences between nematodes are also discussed. BioEssays 25: 221–231, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Certain species of fish have recently become important model systems in comparative genomics and in developmental biology, in certain instances because of their small genome sizes (e.g., in the pufferfish) and, in other cases, because of the opportunity they provide to combine an easily accessible and experimentally manipulable embryology with the power of genetic approaches (e.g., in the zebrafish). The resulting accumulation of genomic information indicates that, surprisingly, many gene families of fish consist of more members than in mammals. (...) Most modern fish, including the zebrafish and medakka, are diploid organisms; however, the greater number of genes in fish was possibly caused by additional ancient genome duplications which happened in the lineage leading to modern ray-finned fishes but not along the lineage leading to tetrapods. Since these two lineages shared their last common ancestor (in the Devonian about 360 million years ago) individual duplicated members of gene families were later lost in fish. Interestingly, comparative data indicate that, in some cases, genes in mammals even serve somewhat different functions than their homologues in fish, highlighting that the degree of evolutionary relatedness of genes is not always a reliable predictor of their evolutionary conservation and their similarity of function. Since fish are phenotypically probably not more complex than mammals, it is possible that evolution took alternative paths to the “economics of genomics” through alternative solutions to gene regulation. It is suggested that the more complex genomic architecture of fish permitted them to adapt and speciate quickly in response to changing selective regimes. BioEssays 20:511–515, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

Oversight of human gene transfer research presents an important model with potential application to oversight of nanobiology research on human participants. Gene therapy oversight adds centralized federal review at the National Institutes of Health's Office of Biotechnology Activities and its Recombinant DNA Advisory Committee to standard oversight of human subjects research at the researcher's institution and at the federal level by the Office for Human Research Protections. The Food and Drug Administration's Center for Biologics Evaluation and Research oversees (...) human gene transfer research in parallel, including approval of protocols and regulation of products. This article traces the evolution of this dual oversight system; describes how the system is already addressing nanobiotechnology in gene transfer: evaluates gene therapy oversight based on public opinion, the literature, and preliminary expert elicitation; and offers lessons of the gene therapy oversight experience for oversight of nanobiotechnology. (shrink)

In this paper we analyse how the risks associated with research on transgenic plants are regulated in Sweden. The paper outlines the way in which pilot projects in the plant sciences are overseen in Sweden, and discusses the international and national background to the current regulatory system. The historical, and hitherto unexplored, reasons for the evolution of current administrative and legislative procedures in plant science are of particular interest. Specifically, we discuss similarities and differences in the regulation of (...) medicine and plant science, and we examine the tendency towards dichotomizing risk — focusing on social/ethical risks in medicine and biological risks in plant science. The context of this article is the Synpraxia research project, an inter-disciplinary program combining expertise in sciences and the humanities. (shrink)

Historically, philosophers of biology have tended to sidestep the problem of development by focusing primarily on evolutionary biology and, more recently, on molecular biology and genetics. Quite often too, development has been misunderstood as simply, or even primarily, a matter of gene activation and regulation. Nowadays a growing number of philosophers of science are focusing their analyses on the complexities of development, and in Embryology, Epigenesis and Evolution Jason Scott Robert explores the nature of development against current (...) trends in biological theory and practice and looks at the interrelations between development and evolution, an area of resurgent biological interest. Clearly written, this book should be of interest to students and professionals in the philosophy of science and the philosophy of biology. (shrink)

Hox complex genes are key developmental regulators highly conserved throughout evolution. The encoded proteins share a 60‐amino‐acid DNA‐binding motif, the homeodomain, and function as transcription factors to control axial patterning. An important question concerns the nature and function of genes acting downstream of Hox proteins. This review focuses on Drosophila, as little is known about this question in other organisms. The noticeable progress gained in the field during the past few years has significantly improved our current understanding of how (...) Hox genes control diversified morphogenesis. Here we summarise the strategies deployed to identify Hox target genes and discuss how their function contributes to pattern formation and morphogenesis. The regulation of target genes is also considered with special emphasis on the mechanisms underlying the specificity of action of Hox proteins in the whole animal. (shrink)

The larval arms of echinoid plutei are used for locomotion and feeding. They are composed of internal calcite skeletal rods covered by an ectoderm layer bearing a ciliary band. Skeletogenesis includes an autonomous molecular differentiation program in primary mesenchyme cells (PMCs), initiated when PMCs leave the vegetal plate for the blastocoel, and a patterning of the differentiated skeletal units that requires molecular cues from the overlaying ectoderm. The arms represent a larval feature that arose in the echinoid lineage during the (...) Paleozoic and offers a subject for the study of gene co-option in the evolution of novel larval features. We isolated new molecular markers in two closely related but differently developing species, Heliocidaris tuberculata and Heliocidaris erythrogramma. We report the expression of a larval arm-associated ectoderm gene tetraspanin, as well as two new PMC markers, advillin and carbonic anhydrase. Tetraspanin localizes to the animal half of blastula stage H. tuberculata and then undergoes a restriction into the putative oral ectoderm and future location of the postoral arms, where it continues to be expressed at the leading edge of both the postoral and anterolateral arms. In H. erythrogramma, its expression initiates in the animal half of blastulae and expands over the entire ectoderm from gastrulation onward. Advillin and carbonic anhydrase are upregulated in the PMCs postgastrulation and localized to the leading edge of the growing larval arms of H. tuberculata but do not exhibit coordinated expression in H. erythrogramma larvae. The tight spatiotemporal regulation of these genes in H. tuberculata along with other ontogenetic and phylogenetic evidence suggest that pluteus arms are novel larval organs, distinguishable from the processes of skeletogenesis per se. The dissociation of expression control in H. erythrogramma suggest that coordinate gene expression in H. tuberculata evolved as part of the evolution of pluteus arms, and is not required for larval or adult development. (shrink)

With the advent of evolutionary developmental research, or EvoDevo, there is hope of discovering the roles that the genetic bases of development play in morphological evolution. Studies in EvoDevo span several levels of organismal organization. Low-level studies identify the ultimate genetic changes responsible for morphological variation and diversity. High-level studies of development focus on how genetic differences affect the dynamics of gene networks and epigenetic interactions to modify morphology. Whereas an increasing number of studies link independent acquisition of (...) homoplastic or convergent morphologies to similar changes in the genomes, homoplasies are not always found to have identical low-level genetic underpinnings. This suggests that a combination of low- and high-level approaches may be useful in understanding the relationship between genetic and morphological variation. Therefore, as an empirical and conceptual framework, we propose the causality horizon to signify the lowest level that allows linking homoplastic morphologies to similar changes in the development. A change in a system below the causality horizon cannot be generalized. In more concrete terms, homoplastic morphologies cannot be reduced to the same change in gene regulation when that change occurs below the causality horizon; rather, a higher-level mechanism should be identified. (shrink)

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

It is often overlooked that, in addition to the integrity of protein‐coding sequences (PCSs), human health is crucially linked to the normal expression of genes by cis‐regulatory sequences (CRSs). These CRSs often lie at some considerable distance from the PCSs whose expression they control and often within other genes. The resulting gene interdigitation can make long‐range CRS identification and characterisation difficult. We propose that the need to conserve long‐range CRSs in cis with their target PCSs through evolution, in (...) combination with gene interdigitation and co‐regulation of many genes by individual CRSs, has contributed to the persistence of conserved synteny blocks between diverse species. We further hypothesise that examination of the varying extents of synteny blocks between multiple species in combination with phylogenetic footprinting to find CRSs might provide important clues to the existence of crucial functional CRS–PCS linkages. Identifying CRS–PCS linkages crucial to human health will lead to a better understanding of how their disruption by CRS mutation or chromosome translocation might contribute to many distressing human diseases. BioEssays 26:1217–1224, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

The heat shock genes (hsp genes) are a family of truly ubiquitous genes which have been highly conserved throughout evolution. The protein products of these genes, the heat shock proteins (hsps) are thought to play a protective role in cells (although this may not be their only function). The genes and their products have been the subjects of intense research both at the cellular and molecular levels over the past few years. This review deals with the conservation of the (...) heat shock response and with the expression of the hsp genes under different conditions: they are usually activated as a group by different forms of stress, but can be expressed individually or in subsets at different stages during normal development and the expression of one of them is evoked by the products of different transforming genes. Experimental approaches which have provided information or which have led to hypotheses regarding the molecular details of the mechanisms regulating the expression of the genes are discussed. (shrink)

The interrelationships among recent theories on the regulation of gene activity and differentiation in higher organisms are reviewed. Interpretations within these theories of the various components of chromosomes are re-evaluated and a unified conceptual framework of hierarchical genetic control mechanisms in eukaryotes is presented.

The sequencing of the human genome has opened the way for using bioinformatics to identify sets of genes controlled by specific regulatory signals. Here, we review the unexpected diversity of DNA response elements mediating transcriptional regulation by estrogen receptors (ERs), which control the broad physiological effects of estrogens. Consensus palindromic estrogen response elements are found in only a few known estrogen target genes, whereas most responsive genes contain only low‐affinity half palindromes, which may also control regulation by other (...) nuclear receptors. ERs can also regulate gene expression in the absence of direct interaction with DNA, via protein–protein interactions with other transcription factors or by modulating the activity of upstream signaling components, thereby significantly expanding the repertoire of estrogen‐responsive genes. These diverse mechanisms of action must be taken into account in screening for potential estrogen‐responsive sequences in the genome or in regulatory regions of target genes identified by expression profiling. BioEssays 24:244–254, 2002. © 2002 Wiley Periodicals, Inc.; DOI 10.1002/bies.10066. (shrink)

In 1995, the eyeless (ey) gene was dubbed the “master‐regulator” of eye development in Drosophila. Not only is ey required for eye development, but its misexpression can convert many other tissues into eye, including legs, wings and antennae.(1) ey is remarkable for its ability to drive coordinate differentiation of the multiple cell types that have to differentiate in a very precise pattern to construct the fly eye, and for its power to override the previous differentiation programs of many other (...) diverse tissues. Even more remarkable, the ey homolog Pax6 and homologs of other eye determination genes from Drosophila are also required for eye development in vertebrates,(2,3) prompting reassessment of the evolution of vision throughout the animal kingdom.(4,5) Now Kumar and Moses have published a study that throws a new light on ey function in Drosophila.(6) According to their work, ey becomes a master regulator of eye development much later than previously thought, and is regulated by signalling through the Notch and EGFR signaling pathways. BioEssays 23:763–766, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Despite decades of research, morphogenesis along the various body axes remains one of the major mysteries in developmental biology. A milestone in the field was the realisation that a set of closely related regulators, called Hox genes, specifies the identity of body segments along the anterior–posterior (AP) axis in most animals. Hox genes have been highly conserved throughout metazoan evolution and code for homeodomain‐containing transcription factors. Thus, they exert their function mainly through activation or repression of downstream genes. However, (...) while much is known about Hox gene structure and molecular function, only a few target genes have been identified and studied in detail. Our knowledge of Hox downstream genes is therefore far from complete and consequently Hox‐controlled morphogenesis is still poorly understood. Genome‐wide approaches have facilitated the identification of large numbers of Hox downstream genes both in Drosophila and vertebrates, and represent a crucial step towards a comprehensive understanding of how Hox proteins drive morphological diversification. In this review, we focus on the role of Hox genes in shaping segmental morphologies along the AP axis in Drosophila, discuss some of the conclusions drawn from analyses of large target gene sets and highlight methods that could be used to gain a more thorough understanding of Hox molecular function. In addition, the mechanisms of Hox target gene regulation are considered with special emphasis on recent findings and their implications for Hox protein specificity in the context of the whole organism. BioEssays 30:965–979, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Theological and secular concepts ofstewardship evolved markedly in the 20thcentury. During this period of evolution, theAmerican Country Life Association through itschurch, academic, farm organization, andgovernmental affiliations, served as a bridgingand bonding agent in developing the stewardshipidea. As in any evolutionary process, thestewardship concept was subjected to a broadarray of influences and characterized bynotable highlights such as the Lynn Smithcritique of the Judaeo-Christian ethic, theman-in-nature statement of Douglas John Hall,and the environmental concerns of ecologistsand philosophers of the post-Rachel Carson era.Some (...) gains have been made in understanding theplace of humans in nature, but the stewardshipidea continues as work in process. (shrink)