Cis‐regulatory elements govern gene expression programs to determine cell identity during development. Recently, the possibility that multiple enhancers are orchestrated in clusters of enhancers has been suggested. How these elements are arranged in the 3D space to control the activation of a specific promoter remains unclear. Our recent work revealed that the TGFβ pathway drives the assembly of enhancer clusters and precise gene activation during neurogenesis. We discovered that the TGFβ pathway coactivator JMJD3 was essential in maintaining these structures in (...) the 3D space. To do that, JMJD3 required an intrinsically disordered region involved in forming phase‐separated biomolecular condensates found in the enhancer clusters. Our data support the existence of a relationship between 3D‐conformation of the chromatin, biomolecular condensates, and TGFβ‐driven response during mammalian neurogenesis. In this review, we discuss how signaling (TGFβ), epigenetics (JMJD3), and biochemical properties (biomolecular condensates nucleation) are coordinated to modulate the genome structure to guarantee proper neural development. Moreover, we comment on the potential underlying mechanisms and implications of the enhancer‐mediated regulation. Finally, we point out the knowledge gaps that still need to be addressed. (shrink)

Recent years have witnessed an explosion of the single-cell biochemical toolbox including chromosome conformation capture -based methods that provide novel insights into chromatin spatial organization in individual cells. The observations made with these techniques revealed that topologically associating domains emerge from cell population averages and do not exist as static structures in individual cells. Stochastic nature of the genome folding is likely to be biologically relevant and may reflect the ability of chromatin fibers to adopt a number (...) of alternative configurations, some of which could be transiently stabilized and serve regulatory purposes. Single-cell Hi-C approaches provide an opportunity to analyze chromatin folding in rare cell types such as stem cells, tumor progenitors, oocytes, and totipotent cells, contributing to a deeper understanding of basic mechanisms in development and disease. Here, we review key findings of single-cell Hi-C and discuss possible biological reasons and consequences of the inferred dynamic chromatin spatial organization. Single-cell Hi-C expands the molecular biology toolbox for studies of chromatin structure in individual cells. This technique allows one to analyze cell-to-cell variability in TAD and loop structure, and to capture chromosome conformation in rare cell types such as oocytes, totipotent cells, and tumor progenitors. (shrink)

Recent years have witnessed an explosion of the single-cell biochemical toolbox including chromosome conformation capture -based methods that provide novel insights into chromatin spatial organization in individual cells. The observations made with these techniques revealed that topologically associating domains emerge from cell population averages and do not exist as static structures in individual cells. Stochastic nature of the genome folding is likely to be biologically relevant and may reflect the ability of chromatin fibers to adopt a number (...) of alternative configurations, some of which could be transiently stabilized and serve regulatory purposes. Single-cell Hi-C approaches provide an opportunity to analyze chromatin folding in rare cell types such as stem cells, tumor progenitors, oocytes, and totipotent cells, contributing to a deeper understanding of basic mechanisms in development and disease. Here, we review key findings of single-cell Hi-C and discuss possible biological reasons and consequences of the inferred dynamic chromatin spatial organization. Single-cell Hi-C expands the molecular biology toolbox for studies of chromatin structure in individual cells. This technique allows one to analyze cell-to-cell variability in TAD and loop structure, and to capture chromosome conformation in rare cell types such as oocytes, totipotent cells, and tumor progenitors. (shrink)

The spatial organization of the genome is intimately linked to its biological function, yet our understanding of higher order genomic structure is coarse, fragmented and incomplete. In the nucleus of eukaryotic cells, interphase chromosomes occupy distinct.

The spatial organization of genomes is becoming increasingly understood. In mammals, where it is most investigated, this organization ties in with transcription, so an important research objective is to understand whether gene activity is a cause or a consequence of genome folding in space. In this regard, the phenomena of X‐chromosome inactivation and reactivation open a unique window of investigation because of the singularities of the inactive X chromosome. Here we focus on the cause–consequence nexus between (...) genome conformation and transcription and explain how recent results about the structural changes associated with inactivation and reactivation of the X chromosome shed light on this problem. (shrink)

Recent systematic studies using newly developed genomic approaches have revealed common mechanisms and principles that underpin the spatial organization of eukaryotic genomes and allow them to respond and adapt to diverse functional demands. Genomes harbor, interpret, and propagate genetic and epigenetic information, and the three‐dimensional (3D) organization of genomes in the nucleus should be intrinsically linked to their biological functions. However, our understanding of the mechanisms underlying both the topological organization of genomes and the various nuclear (...) processes is still largely incomplete. In this essay, we focus on the functional relevance as well as the biophysical properties of common organizational themes in genomes (e.g. looping, clustering, compartmentalization, and dynamics), and examine the interconnection between genome structure and function from this angle. Present evidence supports the idea that, in general, genome architecture reflects and influences genome function, and is relatively stable. However, the answer as to whether genome architecture is a hallmark of cell identity remains elusive. (shrink)

The nuclear envelope shapes the functional organization of the nucleus. Increasing evidence indicates that one of its main components, the nuclear lamina, dynamically interacts with the genome, including the promoter region of specific genes. This seems to occur in a manner that accords developmental significance to these interactions. This essay addresses key issues raised by recent data on the association of nuclear lamins with the genome. We discuss how lamins interact with large chromatin domains and with spatially (...) restricted regions on gene promoters. We address the relationship between these interactions, chromatin modifications and gene expression outcomes. Lamin‐genome contacts are redistributed after cell division and during stem cell differentiation, with evidence of lineage specificity. Thus, we also speculate on a developmental role of lamin interactions with specific genes. Finally, we highlight how concepts arising from this recent work lay the foundations of future challenges and investigations. (shrink)

The perception of the lightness of surfaces has been shown to be affected by information about the spatial configuration of those surfaces and their illuminants. For example, two surfaces of equal luminance can appear to be of very different lightness if one of the two appears to lie in a shadow. How are we to understand the character of the processes that integrate such spatial configuration information so as to yield the eventual appearance of lightness? This paper makes (...) some simple observations about the vocabulary of appearance used in these contexts, and proposes that the end results can be called "phenomenal" in a traditional sense of that word. Processes whose products are phenomenal are next distinguished from processes characterized in other terms: (a) processes of perceptual grouping; (b) processes of perceptual organization; and (c) attentional (as opposed to preattentive) processes. These four categories are conceptually and empirically distinct. In particular, the paper reviews some evidence that appearances as of contours, occlusion, and amodally completed shapes can occur preattentively. Some implications for understanding gestalt grouping processes are briefly discussed. (shrink)

This article attempts to establish analogies between the recent introduction into architectural thought of notions such as the human body movement, events and scenarios, and the development of navigation and interaction principles and conventions in the computer world. The study of the human–computer interface contributes to an understanding of the major role of the computer screen as a point of convergence of different representational forms, and the emergence of new ones belonging to the digital culture. The compositional structure of interactive (...) multimedia works is on the one hand a visual, spatial composition and on the other a narrative and navigational structure. (shrink)

Analysis of the DNA sequence associated with the nuclear matrix has made it possible to identify several types of DNA matrix association. Permanent attachment sites are detected in both transcriptionally active and inactive nuclei. Furthermore, replication origins have been shown to be permanently attached to the nuclear matrix. In transcriptionally active nuclei, expressed genes are also associated with the nuclear matrix. Finally, a special group of attachment sites is described; these sites are believed to maintain the fixed positions of individual (...) chromosomes in interphase nuclei. (shrink)

Early embryogenesis of Caenorhabditis elegans provides a striking example of the generation of polarity and the partitioning of cytoplasmic factors according to this polarity. Microfilaments (MFs) appear to play a critical role in these processes. By visualizing the distribution of MFs and by studying the consequences of disrupting MFs for short, defined periods during zygote development, we have generated some new ideas about when and how microfilaments function in the zygote.

The specificity of eukaryotic DNA organization into loops fixed to the nuclear matrix/chromosomal scaffold has been studied for more than fifteen years. The results and conclusions of different authors remain, however, controversial. Recently, we have elaborated a new approach to the study of chromosomal DNA loops. Instead of characterizing loop basements (nuclear matrix DNA), we have concentrated our efforts on the characterization of individual loops after their excision by DNA topoisomerase II‐mediated DNA cleavage at matrix attachment sites. In this (...) review the results of applying this mapping approach are compared with the results and conclusions from studies of nuclear matrix DNA. An attempt is also made to reconsider all data about the specificity of DNA interactions with the nuclear matrix and to suggest a model of spatial organization of the eukaryotic genome which resolves apparent contradictions between these data. (shrink)

Over the past decade, research has revealed biomolecular condensates' relevance in diverse cellular functions. Through a phase separation process, they concentrate macromolecules in subcompartments shaping the cellular organization and physiology. In the nucleus, biomolecular condensates assemble relevant biomolecules that orchestrate gene expression. We here hypothesize that chromatin condensates can also modulate the nongenetic functions of the genome, including the nuclear mechanical properties. The importance of chromatin condensates is supported by the genetic evidence indicating that mutations in their members (...) are causative of a group of rare Mendelian diseases named chromatinopathies (CPs). Despite a broad spectrum of clinical features and the perturbations of the epigenetic machinery characterizing the CPs, recent findings highlighted negligible changes in gene expression. These data argue in favor of possible noncanonical functions of chromatin condensates in regulating the genome's spatial organization and, consequently, the nuclear mechanics. In this review, we discuss how condensates may impact nuclear mechanical properties, thus affecting the cellular response to mechanical cues and, eventually, cell fate and identity.Chromatin condensates organize macromolecules in the nucleus orchestrating the transcription regulation and mutations in their members are responsible for rare diseases named chromatinopathies. We argue that chromatin condensates, in concert with the nuclear lamina, may also govern the nuclear mechanical properties affecting the cellular response to external cues. (shrink)

Nuclear bodies contribute to non‐random organization of the human genome and nuclear function. Using a major prototypical nuclear body, the Cajal body, as an example, we suggest that these structures assemble at specific gene loci located across the genome as a result of high transcriptional activity. Subsequently, target genes are physically clustered in close proximity in Cajal body‐containing cells. However, Cajal bodies are observed in only a limited number of human cell types, including neuronal and cancer cells. (...) Ultimately, Cajal body depletion perturbs splicing kinetics by reducing target small nuclear RNA (snRNA) transcription and limiting the levels of spliceosomal snRNPs, including their modification and turnover following each round of RNA splicing. As such, Cajal bodies are capable of shaping the chromatin interaction landscape and the transcriptome by influencing spliceosome kinetics. Future studies should concentrate on characterizing the direct influence of Cajal bodies upon snRNA gene transcriptional dynamics.Also see the video abstract here. (shrink)

Recent and not so recent advances in our molecular understanding of the genome make the once prevalent view of the genome as a passive container of genetic information (i.e., genes) untenable, and emphasize the importance of the internal organization and re-organization dynamics of the genome for both development and evolution. While this conclusion is by now well accepted, the construction of a comprehensive conceptual framework for studying the genome as a dynamic system, capable of (...) self-organization and adaptive behavior is still underway. This work deals with the effect of such a conceptual shift on evolutionary thought. Specifically, I try to articulate the conceptual commitments and obligations of views that privilege explanatorily or causally the genome, its dynamics and mechanisms, over genes. I refer to this class of views as belonging to ‘the genome perspective’. (shrink)

Genomes are defined by their primary sequence. The functional properties of genomes, however, are determined by far more complex mechanisms and depend on multiple layers of regulatory control processes. A key emerging contributor to genome function is the architectural organization of the cell nucleus. The spatial and temporal behavior of genomes and their regulatory proteins are now being recognized as important, yet still poorly understood, control mechanisms in genome function. Combined cell biological, molecular and computational analysis (...) of architectural aspects of genome function has added a further dimension to the investigation of some of the most fundamental cellular processes including transcription and maintenance of genome integrity. The complete elucidation of the contribution that nuclear architecture makes to gene expression will be required to fully understand physiological processes such as differentiation, development and disease at the cellular level. Here I give an overview of some of the emerging concepts in the study of in vivo genome organization and function. BioEssays 27:477–487, 2005. Published 2005 Wiley Periodicals, Inc. (shrink)

A hypothesis of genome structural evolution is explored. Rapid and cohesive alterations in genome organization are viewed as resulting from the dynamic and constrained interactions of chromosomal subsystem components. A combination of macromolecular boundary conditions and DNA element involvement in far-from-equilibrium reactions is proposed to increase the complexity of genomic subsystems via the channelling of genome turnover; interactions between subsystems create higher-order subsystems expanding the phase space for further genetic evolution. The operation of generic constraints on (...) structuration in genome evolution is suggested by i) universal, homoplasic features of chromosome organization and ii) the metastable nature of genome structures where lower-level flux is constrained by higher-order structures. Phenomena such as genomic shock, bursts of transposable element activity, concerted evolution, etc., are hypothesized to result from constrained systemic responses to endogenous/exogenous, micro/macro perturbations. The constraints operating on genome turnover are expected to increase with chromosomal structural complexity, the number of interacting subsystems, and the degree to which interactions between genomic components are tightly ordered. (shrink)

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

How genomic innovation translates into organismal organization remains largely unanswered. Possessing the largest invertebrate nervous system, in conjunction with many species‐specific organs, coleoid cephalopods (octopuses, squids, cuttlefishes) provide exciting model systems to investigate how organismal novelties evolve. However, dissecting these processes requires novel approaches that enable deeper interrogation of genome evolution. Here, the existence of specific sets of genomic co‐evolutionary signatures between expanded gene families, genome reorganization, and novel genes is posited. It is reasoned that their co‐evolution (...) has contributed to the complex organization of cephalopod nervous systems and the emergence of ecologically unique organs. In the course of reviewing this field, how the first cephalopod genomic studies have begun to shed light on the molecular underpinnings of morphological novelty is illustrated and their impact on directing future research is described. It is argued that the application and evolutionary profiling of evolutionary signatures from these studies will help identify and dissect the organismal principles of cephalopod innovations. By providing specific examples, the implications of this approach both within and beyond cephalopod biology are discussed. (shrink)

Modern biology has been heavily influenced by the gene‐centric concept. Paradoxically, this very concept – on which bioresearch is based – is challenged by the success of gene‐based research in terms of explaining evolutionary theory. To overcome this major roadblock, it is essential to establish new theories, to not only solve the key puzzles presented by the gene‐centric concept, but also to provide a conceptual framework that allows the field to grow. This paper discusses a number of paradoxes and illustrates (...) how they can be addressed by the genome‐centric concept in order to further resynthesize evolutionary theory. In particular, methodological breakthroughs that analyze genome evolution are discussed. The multiple interactions among different levels of a complex system provide the key to understanding the relationship between self‐organization and natural selection. Darwinian natural selection applies to the biological level due to its unique genetic and heterogeneous features, but does not simply or directly apply to either the lower non‐living level or higher intellectual society level. At the complex bio‐system level, the genome context (the entire package of genes and their genomic physical relationship or genomic topology), not the individual genes, defines the system and serves as the principle selection platform for evolution. (shrink)

High‐throughput DNA analyses are increasingly being used to detect rare mutations in moderately sized genomes. These methods have yielded genome mutation rates that are markedly higher than those obtained using pre‐genomic strategies. Recent work in a variety of organisms has shown that mutation rate is strongly affected by sequence context and genome position. These observations suggest that high‐throughput DNA analyses will ultimately allow researchers to identify trans‐acting factors and cis sequences that underlie mutation rate variation. Such work should (...) provide insights on how mutation rate variability can impact genome organization and disease progression. (shrink)

Recent investigations have revealed 1) that the isochores of the human genome group into two super‐families characterized by two different long‐range 3D structures, and 2) that these structures, essentially based on the distribution and topology of short sequences, mold primary chromatin domains (and define nucleosome binding). More specifically, GC‐poor, gene‐poor isochores are low‐heterogeneity sequences with oligo‐A spikes that mold the lamina‐associated domains (LADs), whereas GC‐rich, gene‐rich isochores are characterized by single or multiple GC peaks that mold the topologically associating (...) domains (TADs). The formation of these “primary TADs” may be followed by extrusion under the action of cohesin and CTCF. Finally, the genomic code, which is responsible for the pervasive encoding and molding of primary chromatin domains (LADs and primary TADs, namely the “gene spaces”/“spatial compartments”) resolves the longstanding problems of “non‐coding DNA,” “junk DNA,” and “selfish DNA” leading to a new vision of the genome as shaped by DNA sequences. (shrink)

The coordinated expression of the Hox gene family encoding transcription factors is critical for proper embryonic development and patterning. Major efforts have thus been dedicated to understanding mechanisms controlling Hox expression. In addition to the temporal and spatial sequential activation of Hox genes, proper embryonic development requires that Hox genes get differentially silenced in a cell‐type specific manner as development proceeds. Factors contributing to Hox silencing include the polycomb repressive complexes (PRCs), which control gene expression through epigenetic modifications. This (...) review focuses on PRC‐dependent regulation of the Hox genes and is aimed at integrating the growing complexity of PRC functional properties in the context of Hox regulation. In particular, mechanisms underlying PRC binding dynamics as well as a series of studies that have revealed the impact of PRC on the 3D organization of the genome is discussed, which has a significant role on Hox regulation during development. (shrink)

Since the late 1990s, the characterization of complete DNA sequences for a large and taxonomically diverse set of species has continued to gain in speed and accuracy. Sequence analyses have indicated a strikingly baroque structure for most eukaryotic genomes, with multiple repeats of DNA sequences and with very little of the DNA specifying proteins. Much of the DNA in these genomes has no known function. These results have generated strong interest in the factors that govern the evolution of genome (...) architecture. While adaptationist ‘just so’ stories have been offered, recent theoretical analyses based on mathematical population genetics strongly suggest that non-adaptive processes dominate genome architecture evolution. This article critically synthesizes and develops these arguments, explicating a core argument along with several variants. It provides a critical assessment of the evidence that supports these arguments’ premises. It also analyses adaptationist responses to these arguments and notes potential problems with the core argument. These theoretical analyses continue the molecular reinterpretation of evolution initiated by the neutral theory in 1968. The article ends by noting that some of these arguments can also be extended to evolution at higher levels of organization which raises questions about adaptationism in general. This remains a puzzle because there is probably little reason to doubt that many organismic features are genuine adaptations. 1 Introduction2 Preliminaries: Senses of Adaptationism3 Genome Architecture3.1 Surprises of early eukaryotic genetics3.2 Genome structure, post-20014 The Case against Adaptationism4.1 Just so stories versus population genetics4.2 The core argument4.3 Three variants of the core argument4.4 Examples: Non-adaptive features of the genome5 Adaptationist Responses6 Concluding Remarks. (shrink)

The Human Genome Decoding Project is progressing rapidly and the full sequences of the 3.2 bilions bases and its representation on the 23 chromosomes will be completed by 2003. The ethical impact of such innovative knowledge for Humankind is relevant. Who will detect the property of this informations and which organization will decide on its potential applications? The anthropological and philosophical implications of these innovative knowledges are presented and discussed.

In lieu of an abstract, here is a brief excerpt of the content:Human Genome Research in an Interdependent WorldAlexander Morgan Capron (bio)This has been the year of agenda-setting conferences for the ambitious ELSI (ethical, legal and social issues) program of the Human Genome Project (HGP). But of the dozen or more major meetings of this sort held across the country, the one held at the National Institutes of Heakh (NIH) in Bethesda, MD, June 2-4, 1991, was distinctive in (...) several respects.1As its name implies, "Human Genome Research in an Interdependent World" was a global look at the issues raised by gene mapping and sequencing. Unlike previous conferences, however, this meeting looked beyond a comparative analysis of clinical and domestic legal issues, and concentrated on topics that may require responses on a truly international level if they are to be successfully resolved.The meeting's organizers gathered an impressive group of more than seventy participants from fifteen countries, including the first significant contingent of Soviet and Japanese scientists, physicians, and philosophers at an ELSI meeting. In addition to talks by the heads of the genome projects in the Soviet Union, Japan, and the United States, the meeting was keynoted by Dr. James Wyngaarden, director general of the Human Genome Organization (HUGO), and I had the honor of serving as its general chairman.The goal of the meeting was to consider an array of issues that scientists, philosophers, and lawyers from around the world suggested might have international significance, with an eye to deciding three things: (1) Does the issue deserve further attention? (2) Is the issue best addressed in an international or domestic context? and (3) Do structures exist to which the issue can be referred for resolution? In the final sessions, the entire group debated proposed resolutions on the various topics and narrowed the list needing further, intensive exploration.To provide an international framework for this process, the conference [End Page 247] established a Global Steering Committee on Ethical and Social Issues in Genome Research, which will coordinate the efforts of several task forces charged with refining the tentative resolutions adopted by the conference participants on June 4. The task forces are expected to be able to complete work on some topics by the time of the steering committee's first meeting, which was described by one participant as a "check point," probably within the coming year; on other topics, the task forces will provide interim reports and arrange to continue their analysis. Several topics—less complex or more embryonic—were referred directly to the steering committee. On all issues, a major objective will be to ascertain what existing or newly created structure or structures are capable of implementing the group's recommendations and then to monitor the issue to ensure that appropriate implementation is occurring.Issues to be Explored by Task ForcesInsurance and EmploymentWhile individuals may derive medically useful information from the expanded range of genetic tests that will flow from the HGP, they could also be harmed if test results become a basis for discrimination. An area of particular concern at the conference in Bethesda was whether genetic information should be used to decide eligibility for employment or the scope and cost of health and life insurance. The complexity of this issue is increased as barriers to worker migration fall (especially in Europe) and as more firms carry on business internationally. Furthermore, questions arise about the limits of required testing and whether individuals may decline to be informed of the results of tests.The task force will not only gather information on practices and legal standards throughout the world—especially in light of the differences among nations with regard to the linkage of employment and various forms of insurance—but will also examine international anti-discrimination laws as a possible means of supplementing domestic statutes and regulations. As a starting point, the Bethesda meeting agreed on a set of principles for the task force to refine.2ForensicsAlthough their legal status is not fully resolved, DNA tests are being used increasingly in judicial proceedings and civil and criminal investigations as a highly probative means to identify people. Most forensic uses of "DNA fingerprints" are domestic, but international cooperation among investigative bodies... (shrink)

The recent ability to inactivate specific genes in mice has significantly accelerated our understanding of molecular, cellular, and even behavioral aspects of normal and disease processes. However, this ability has also demonstrated the extreme complexity of genetic determination in mammals, in particular, that genes in the same family or pathway can be functionally redundant and that a given gene often has multiple roles. Thus, inactivation of a gene often does not indicate its complete spectrum of functions. To circumvent this problem, (...) many new tools and novel applications of classic techniques have been developed to place spatial and temporal restrictions on the genomic alterations. These approaches include chimera and mosaic studies, organ transplantation, complementation assays, dominant negative mutants, conditional gene knockouts, and lineage-specific gene rescue. Not only has this opened up more sophisticated ways to make genomic alterations, but it has provided the opportunity to create animal models for sporadic human genetic diseases. BioEssays 20:200–208, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

Chromosomes are not randomly packed and positioned into the nucleus but folded in higher‐order chromatin structures with defined functions. However, the genome of a fertilized embryo undergoes a dramatic epigenetic reprogramming characterized by extensive chromatin relaxation and the lack of a defined three‐dimensional structure. This reprogramming is followed by a slow genome refolding that gradually strengthens the chromatin architecture during preimplantation development. Interestingly, genome refolding during early development coincides with a progressive loss of developmental potential suggesting a (...) link between chromatin organization and cell plasticity. In agreement, loss of chromatin architecture upon depletion of the insulator transcription factor CTCF in embryonic stem cells led to the upregulation of the transcriptional program found in totipotent cells of the embryo, those with the highest developmental potential. This essay will discuss the impact of genome folding in controlling the expression of transcriptional programs involved in early development and their plastic‐associated features. (shrink)

In addressing the creation and regulation of biobanks in different countries, a short descriptive introduction to the social and cultural backgrounds of each country is mandatory. The State of Israel is relatively young, and can be characterized as a multi-religious, multi-ethnic, multi-cultural society, somewhat similar to the American melting pot. The current population is 8.3 million, a sharp rise resulting from a 1.2 million influx of immigrants from the former Soviet Union in the 1990s. Seventyfive percent are Jewish, 20% Arabs, (...) and several other minorities. The birth rate is 3.8 per family, the highest in the Organization for Economic Cooperation and Development. (shrink)

Mitochondrial genomes represent relict bacterial genomes derived from a progenitor α‐proteobacterium that gave rise to all mitochondria through an ancient endosymbiosis. Evolution has massively reduced these genomes, yet despite relative simplicity their organization and expression has developed considerable novelty throughout eukaryotic evolution. Few organisms have reengineered their mitochondrial genomes as thoroughly as the protist lineage of dinoflagellates. Recent work reveals dinoflagellate mitochondrial genomes as likely the most gene‐impoverished of any free‐living eukaryote, encoding only two to three proteins. The (...) class='Hi'>organization and expression of these genomes, however, is far from the simplicity their gene content would suggest. Gene duplication, fragmentation, and scrambling have resulted in an inflated and complex genome organization. Extensive RNA editing then recodes gene transcripts, and trans‐splicing is required to assemble full‐length transcripts for at least one fragmented gene. Even after these processes, messenger RNAs (mRNAs) lack canonical start codons and most transcripts have abandoned stop codons altogether. (shrink)

Abstract“Development” suggests that there is something that is developing, or changing over time. We can ask about temporal boundaries of that developmental process, asking when development begins or ends and whether it has defined stages along the way, for example. We can ask about spatial boundaries as well: where does the developing object start and end? For this article, I ask about the boundary definition of the developing organism in particular. What is an individual organism, and what defines it (...) as the same organism as it changes over time? In particular, how has this been answered historically: how have researchers described and explained what an individual developing organism is? This article explores ideas and approaches especially starting in the late 19th century, and in particular looks at the role of “organization.”. (shrink)

The view advanced by Madole & Harden falls back on the dogma of a gene as a DNA sequence that codes for a fixed product with an invariant function regardless of temporal and spatial contexts. This outdated perspective entrenches the metaphor of genes as static units of information and glosses over developmental complexities.

The aim of this paper is to compare various methods for the quantification of metabolic pathways dynamics. A Yates-Pardee metabolic pathway with enzyme organization, i.e. with spatial localization of the enzymes in a specific cellular compartment, was studied using: (i) the classical Henri-Michaelis-Menten (HMM) equations, (ii) linearization of the HMM equations in the vicinity of a steady state (linearized formalism), and (iii) Biochemical Systems Theory formalism (BST formalism). It is shown that transient solutions computed via either the linearized (...) formalism or the BST formalism can greatly differ from transient solutions computed with the HMM equations. However, in the studied example, results remain qualitatively the same for the three formalisms. This suggests that the study of the topology of the system may give useful insights into the metabolic pathways dynamics. (shrink)