Natural selection is an important force that shapes the evolution of all living things by determining which individuals contribute the most descendents to future generations. The biological unit upon which selection acts has been the subject of serious debate, with reasonable arguments made on behalf of populations, individuals, individual phenotypic characters and, finally, individual genes themselves. In this essay, I argue that the usual unit of selection is the gene. There are powerful logical arguments in favor of this conclusion, as (...) well as many real-world examples. I also explore the possibility that epigenetic differences between individuals may be heritable between generations. Although few such examples exist, epigenetic differences provide an exciting source of potentially heritable variation that may allow rapid evolutionary change to occur, perhaps in response to environmental influences. (shrink)

This chapter contains sections titled: Introduction Natural Selection Operates within Genomes without Regard for Phenotypic Effect Selective Forces, Heritable Variation, and the Definition of Function Natural Selection Can, and Does, Act on the Products of Individual Genes Natural Selection Can Act Directly on Genes Themselves What Are the Limitations on the Unit of Selection Being “the Gene”? The “Complexity” Argument: Do Complex Phenotypes Require Complex Explanations? Do “Epigenes/Epialleles” Provide a “Non‐genetic” Source of Heritable Variation Upon Which Natural Selection May Act? (...) Summary Points: The Usual Unit of Selection Is the Gene Postscript: Counterpoint Note References. (shrink)

It has been unclear why certain defined DNA regions are consistently sites of chromosomal translocations. Some of these are simply sequences of recognition by endogenous recombination enzymes, but most are not. Recent progress indicates that some of the most common fragile sites in human neoplasm assume non‐B DNA structures, namely deviations from the Watson–Crick helix. Because of the single strandedness within these non‐B structures, they are vulnerable to structure‐specific nucleases. Here we summarize these findings and integrate them with other recent (...) data for non‐B structures at sites of consistent constitutional chromosomal translocations. BioEssays 28: 480–494, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Studies on Neurospora chromosome segment duplications (Dps) performed since the publication of Perkins's comprehensive review in 1997 form the focus of this article. We present a brief summary of Perkins's seminal work on chromosome rearrangements, specifically, the identification of insertional and quasiterminal translocations that can segregate Dp progeny when crossed with normal sequence strains (i.e., T × N). We describe the genome defense process called meiotic silencing by unpaired DNA that renders Dp‐heterozygous crosses (i.e., Dp × N) barren, which provides (...) a basis for identifying Dps, and discuss whether other processes also might contribute to the barren phenotype of Dp × N and Dp × Dp crosses. We then turn to studies suggesting that large Dps (i.e., >300 kbp) can allow smaller gene‐sized duplications to escape another genome defense process called repeat‐induced point mutation (RIP), possibly by titration of the RIP machinery. Finally, we assess whether in natural populations dominant RIP suppressor Dps provide an “RIP‐free” niche for evolution of new genes following the duplication of existing genes. (shrink)

Genome maintenance requires various nucleoid-associated factors in prokaryotes. Among them, the SMC protein has been thought to play a static role in the organization and segregation of the chromosome during cell division. However, recent studies have shown that the bacterial SMC is required to align left and right arms of the emerging chromosome and that the protein dynamically travels from origin to Ter region. A rod form of the SMC complex mediates DNA bridging and has been recognized as a machinery (...) responsible for DNA loop extrusion, like eukaryotic condensin or cohesin complexes, which act as chromosome organizers. Attention is now turning to how the prototype of the complex is loaded on the entry site and translocated on chromosomal DNA, explaining its overall conformational changes at atomic levels. Here, we review and highlight recent findings concerning the prokaryotic SMC complex and discuss possible mechanisms from the viewpoint of protein architecture. Recent studies show dynamic movements of the prokaryotic SMC protein complex: initial loading, translocation on DNA for bacterial chromosome organization. The recent structural models of the protein also provide a new vision for the structure-function relationship. (shrink)

The objectives of this study were to develop a high-density chromosome bin map of homoeologous group 7 in hexaploid wheat, to identify gene distribution in these chromosomes, and to perform comparative studies of wheat with rice and barley. We mapped 2148 loci from 919 EST clones onto group 7 chromosomes of wheat. In the majority of cases the numbers of loci were significantly lower in the centromeric regions and tended to increase in the distal regions. The level of (...) duplicated loci in this group was 24% with most of these loci being localized toward the distal regions. One hundred nineteen EST probes that hybridized to three fragments and mapped to the three group 7 chromosomes were designated landmark probes and were used to construct a consensus homoeologous group 7 map. An additional 49 probes that mapped to 7AS, 7DS, and the ancestral translocated segment involving 7BS also were designated landmarks. Landmark probe orders and comparative maps of wheat, rice, and barley were produced on the basis of corresponding rice BAC/PAC and genetic markers that mapped on chromosomes 6 and 8 of rice. Identification of landmark ESTs and development of consensus maps may provide a framework of conserved coding regions predating the evolution of wheat genomes. (shrink)

Telomeres play a vital role in protecting the ends of chromosomes and preventing chromosome fusion. The failure of cancer cells to properly maintain telomeres can be an important source of the chromosome instability involved in cancer cell progression. Telomere loss results in sister chromatid fusion and prolonged breakage/fusion/bridge (B/F/B) cycles, leading to extensive DNA amplification and large deletions. These B/F/B cycles end primarily when the unstable chromosome acquires a new telomere by translocation of the ends of other (...) class='Hi'>chromosomes. Many of these translocations are nonreciprocal, resulting in the loss of the telomere from the donor chromosome, providing a mechanism for transfer of instability from one chromosome to another until a chromosome acquires a telomere by a mechanism other than nonreciprocal translocation. B/F/B cycles can also result in other forms of chromosome rearrangements, including double‐minute chromosomes and large duplications. Thus, the loss of a single telomere can result in instability in multiple chromosomes, and generate many of the types of rearrangements commonly associated with human cancer. BioEssays 26:1164–1174, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

The nature of the forces that move chromosomes in mitosis is beginning to be revealed. The kinetochore, a specialized structure situated at the primary constriction of the chromosome, appears to translocate in both directions along the microtubules of the mitotic spindle. One or more members of the newly described families of microtubule motor molecules may power these movements. Microtubules of the mitotic spindle undergo rapid cycles of assembly and disassembly. These microtubule dynamics may contribute toward generating force and regulating (...) direction in chromosome movement. (shrink)

Many organisms face a dilemma rooted in the unequal numbers of X chromosomes carried by the two sexes and the need to maintain equivalent expression of X‐linked genes. Several strategies have arisen to cope with this problem. All rely on accurately targeting epigenetic modifications to entire chromosomes. Targeting results from the action of recognition elements that attract modification and may rely on spreading of modification in cis along the affected chromosome. A recent report describing the first X chromosome (...) recognition element from C. elegans opens the way to defining the relative contributions of these factors to the compensation of X‐linked gene expression in worms.1 Extrachromosomal arrays composed of a C. elegans recognition element attract proteins that modify the C. elegans X chromosomes and interact genetically with mutations disrupting compensation. Moreover, examination of X:A translocations provides the first evidence for spreading of modification along C. elegans X chromosomes. BioEssays 26:707–710, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

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

Loss of the Y‐chromosome is a common feature of species with chromosomal sex determination. However, our understanding of why some lineages frequently lose Y‐chromosomes while others do not is limited. The fragile Y hypothesis proposes that in species with chiasmatic meiosis the rate of Y‐chromosome aneuploidy and the size of the recombining region have a negative correlation. The fragile Y hypothesis provides a number of novel insights not possible under traditional models. Specifically, increased rates of Y aneuploidy may impose (...) positive selection for (i) gene movement off the Y; (ii) translocations and fusions which expand the recombining region; and (iii) alternative meiotic segregation mechanisms (achiasmatic or asynaptic). These insights as well as existing evidence for the frequency of Y‐chromosome aneuploidy raise doubt about the prospects for long‐term retention of the human Y‐chromosome despite recent evidence for stable gene content in older non‐recombining regions. (shrink)

Enzymatic misrepair of ionizing‐radiation‐induced DNA damage can produce large‐scale rearrangements of the genome, such as translocations and dicentrics. These and other chromosome exchange aberrations can cause major phenotypic alterations, including cell death, mutation and neoplasia. Exchange formation requires that two (or more) genomic loci come together spatially. Consequently, the surprisingly rich aberration spectra uncovered by recently developed techniques, when combined with biophysically based computer modeling, help characterize large‐scale chromatin architecture in the interphase nucleus. Most results are consistent with a picture (...) whereby chromosomes are mainly confined to territories, chromatin motion is limited, and interchromosomal interactions involve mainly territory surfaces. Aberration spectra and modeling also help characterize DNA repair/misrepair mechanisms. Quantitative results for mammalian cells are best described by a breakage‐and‐reunion model, suggesting that the dominant recombinational mechanism during the G0/G1 phase of the cell cycle is non‐homologous end‐joining of radiogenic DNA double strand breaks. In turn, better mechanistic and quantitative understanding of aberration formation gives new insights into health‐related applications. BioEssays 24:714–723, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

A total of 1918 loci, detected by the hybridization of 938 expressed sequence tag unigenes from 26 Triticeae cDNA libraries, were mapped to wheat homoeologous group 4 chromosomes using a set of deletion, ditelosomic, and nulli-tetrasomic lines. The 1918 EST loci were not distributed uniformly among the three group 4 chromosomes; 41, 28, and 31% mapped to chromosomes 4A, 4B, and 4D, respectively. This pattern is in contrast to the cumulative results of EST mapping in all homoeologous (...) groups, as reported elsewhere, that found the highest proportion of loci mapped to the B genome. Sixty-five percent of these 1918 loci mapped to the long arms of homoeologous group 4 chromosomes, while 35% mapped to the short arms. The distal regions of chromosome arms showed higher numbers of loci than the proximal regions, with the exception of 4DL. This study confirmed the complex structure of chromosome 4A that contains two reciprocal translocations and two inversions, previously identified. An additional inversion in the centromeric region of 4A was revealed. A consensus map for homoeologous group 4 was developed from 119 ESTs unique to group 4. Forty-nine percent of these ESTs were found to be homoologous to sequences on rice chromosome 3, 12% had matches with sequences on other rice chromosomes, and 39% had no matches with rice sequences at all. Limited homology was found between wheat ESTs on homoeologous group 4 and the Arabidopsis genome. Forty-two percent of the homoeologous group 4 ESTs could be classified into functional categories on the basis of blastX searches against all protein databases. (shrink)

Recent mutagenesis studies have demonstrated that the chemotherapeutic agent, chlorambucll (CHL), is highly mutagenic in male germ cells of the mouse. Post‐melotic germ cells, and especially early spermatids, are the most sensitive to the cytotoxic and mutagenic effects of this agent. Genetic, cytogenetic and molecular analyses of many induced mutations have shown that, in these germ‐cell stages, CHL induces predominantly chromosomal rearrangements (deletions and translocations), and mutation‐rate studies show that, in terms of tolerated doses, CHL is perhaps five to ten (...) times more efficient in inducing rearrangements than is radiation exposure. Appropriate breeding protocols, along with knowledge of the advantages and limitations associated with the use of CHL, can be used to expand the current resource of chromosomal rearrangements in the mouse and to provide new phenotype‐associated mutations amenable to positional‐cloning techniques. The analysis of CHL‐induced mutations has also contributed to understanding the factors that affect the yield and nature of chemically induced germline mutations in mammals. (shrink)

Mammalian cells frequently depend on homologous recombination (HR) to repair DNA damage accurately and to help rescue stalled or collapsed replication forks. The essence of HR is an exchange of nucleotides between identical or nearly identical sequences. Although HR fulfills important biological roles, recombination between inappropriate sequence partners can lead to translocations or other deleterious rearrangements and such events must be avoided. For example, the recombination machinery must follow stringent rules to preclude recombination between the many repetitive elements in a (...) mammalian genome that share significant but imperfect homology. This paper takes a conceptual approach in addressing the homology requirements for recombination in mammalian genomes as well as the general strategy used by cells to reject recombination between similar but imperfectly matched sequences. A mechanism of heteroduplex rejection that involves the unwinding of recombination intermediates that may form between mismatched sequences is discussed. BioEssays 30:1163–1171, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

This chapter offers a review of standard views about the requirements for natural selection to shape evolution and for the sorts of ‘units’ on which selection might operate. It then summarizes traditional arguments for genic selectionism, i.e., the view that selection operates primarily on genes (e.g., those of G. C. Williams, Richard Dawkins, and David Hull) and traditional counterarguments (e.g., those of William Wimsatt, Richard Lewontin, and Elliott Sober, and a diffuse group based on life history strategies). It then offers (...) a series of responses to the arguments, based on more contemporary considerations from molecular genetics, offered by Carmen Sapienza. A key issue raised by Sapienza concerns the degree to which a small number of genes might be able to control much of the variation relevant to selection operating on such selectively critical organs as hearts. The response to these arguments suggests that selection acts on many levels at once and that sporadic selection, acting with strong effects, can act successively on different key traits (and genes) while maintaining a balance among many potentially conflicting demands faced by organisms within an evolving lineage. (shrink)

This chapter offers a review of standard views about the requirements for natural selection to shape evolution and for the sorts of ‘units’ on which selection might operate. It then summarizes traditional arguments for genic selectionism, i.e., the view that selection operates primarily on genes (e.g., those of G. C. Williams, Richard Dawkins, and David Hull) and traditional counterarguments (e.g., those of William Wimsatt, Richard Lewontin, and Elliott Sober, and a diffuse group based on life history strategies). It then offers (...) a series of responses to the arguments, based on more contemporary considerations from molecular genetics, offered by Carmen Sapienza. A key issue raised by Sapienza concerns the degree to which a small number of genes might be able to control much of the variation relevant to selection operating on such selectively critical organs as hearts. The response to these arguments suggests that selection acts on many levels at once and that sporadic selection, acting with strong effects, can act successively on different key traits (and genes) while maintaining a balance among many potentially conflicting demands faced by organisms within an evolving lineage. (shrink)

According to the somatic mutation theory (SMT), cancer begins with a genetic change in a single cell that passes it on to its progeny, thereby generating a clone of malignant cells. It is strongly supported by observations of leukemias that bear specific chromosome translocations, such as Burkitt's lymphoma, in which a translocation activates the c‐myc gene, and chronic myeloid leukemia (CML), in which the Philadelphia chromosome causes production of the BCR‐ABL oncoprotein. Although the SMT has been modified and extended (...) to encompass tumor suppressor genes, epigenetic inheritance, and tumor progression through accumulation of further mutations, perhaps the strongest validation comes from the successful treatment of certain malignancies with drugs that directly target the product of the mutant gene.magnified imageDavid Vaux is at the Walter and Eliza Hall Institute and La Trobe Institute for Molecular Science, Melbourne, Australia. (shrink)

SCL (TAL1/TCL5) is a member of the helix‐loop‐helix family of transcription factors. Originally identified because of its involvement in a tumour‐specific chromosomal translocation, overexpression of the SCL gene is the most common molecular abnormality found in human T cell leukaemia. Transgenic models have now formally demonstrated that overexpression of SCL within the T cell lineage is capable of causing malignant transformation. Gene targeting experiments have revealed that the SCL gene is crucial for the development of primitive haematopoiesis in the (...) mouse and is also required for the generation of all adult haematopoietic lineages. Biochemical studies have indicated some of the proteins which interact with SCL and this has refined the hypotheses concerning the mechanisms by which SCL plays a role in leukaemogenesis and haematopoietic development. (shrink)

Cellular events must be executed in a certain sequence during the cell division in order to maintain genome integrity and hence ensure a cell's survival. In M phase, for instance, chromosome segregation always precedes mitotic exit (characterized by mitotic kinase inactivation via cyclin destruction); this is then followed by cytokinesis. How do cells impose this strict order? Recent findings in budding yeast have suggested a mechanism whereby partitioning of chromosomes into the daughter cell is a prerequisite for the activation (...) of mitotic exit network (MEN). So far, however, a regulatory scheme that would temporally link the initiation of cytokinesis to the execution of mitotic exit has not been determined. We propose that the requirement of MEN components for cytokinesis, their translocation to the mother–daughter neck and triggering of this translocation by inactivation of the mitotic kinase may be the three crucial elements that render initiation of cytokinesis dependent on mitotic exit. BioEssays 24: 659–666, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

Duchenne muscular dystrophy (DMD) is a progressive and lethal neuromuscular disorder caused by a defective gene on the X chromosome. There is no effective treatment and the biochemical defect is yet unknown. Mapping of the DMD locus to band Xp21 in the short arm of the X chromosome has given rise to strategies to clone the gene from its known location in the chromosome. Two cloning strategies have led to the isolation of a gene that is the largest of any (...) yet described. Portions of the gene are deleted in about 8% of affected males, and rare translocations that disrupt the gene cause the disease in females. The isolation of expressed sequences from the DMD locus will undoubtedly lead to isolation of the gene product and ultimately to an understanding of the basic defect. In the meantime, DNA probes from the DMD locus provide a new and accurate approach for carrier identification and prenatal diagnosis of this dreaded disease. (shrink)

Illuminating insights into lymphoid oncogenesis came with the finding that the chromosome translocations characteristic of many tumors of immunoglobulin‐producing cells represent conjunction of an immunoglobulin gene locus with the myc oncogene. The potency of this combination has been underlined by recent studies in which DNA regions mimicking certain chromosome junctions of lymphomas were shown to be highly tumorigenic when inserted into the mouse germline. Nevertheless, the mechanism by which an immunoglobulin locus activates the oncogene remains largely an enigma, particularly in (...) those cases where the two loci remain at some distance. (shrink)

Tumour‐associated genetic changes frequently involve DNA translocation or deletion. Many of these events will have arisen from initial genomic damage, induced by either the activity of endogenous metabolic processes or from exposure to environmental genotoxic agents. Although initial genomic damage will have been widely distributed, tumorigenic events are confined to certain DNA target sites. Furthermore, within these target sites there appear to be regions of preferential DNA rearrangement, and examination of these sites implies that the location and extent of (...) such rearrangement may be influenced by DNA primary and secondary structure rather than simply by the point of damage. We selectively review evidence relating to DNA structures that may predispose certain regions of the genome to damage‐induced rearrangement, and discuss the possible role of interstitial, inverted telomere‐like sequence arrays in promoting chromosomal events of a type known to be associated with some human and animal tumours. (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)

Phage DNA packaging occurs by DNA translocation into a prohead. Terminases are enzymes which initiate DNA packaging by cutting the DNA concatemer, and they are closely fitted structurally to the portal vertex of the prohead to form a ‘packasome’. Analysis among a number of phages supports an active role of the terminases in coupling ATP hydrolysis to DNA translocation through the portal. In phage T4 the small terminase subunit promotes a sequence‐specific terminase gene amplification within the chromosome. This (...) link between recombination and packaging suggests a DNA synapsis mechanism by the terminase to control packaging initiation, formally homologous to eukaryotic chromosome segregation. (shrink)

Secretion systems enable bacteria to import and secrete large macromolecules including DNA and proteins. While most components of these systems have been identified, the molecular mechanisms of macromolecular transport remain poorly understood. Recent findings suggest that various bacterial secretion systems make use of the translocation ratchet mechanism for transporting polymers across the cell envelope. Translocation ratchets are powered by chemical potential differences generated by concentration gradients of ions or molecules that are specific to the respective secretion systems. Bacteria (...) employ these potential differences for biasing Brownian motion of the macromolecules within the conduits of the secretion systems. Candidates for this mechanism include DNA import by the type II secretion/type IV pilus system, DNA export by the type IV secretion system, and protein export by the type I secretion system. Here, we propose that these three secretion systems employ different molecular implementations of the translocation ratchet mechanism. Brownian ratchets are often discussed in the context of directed molecular movement. Bacterial secretion systems transport molecules through membranes in a directed fashion. Here, we focus on recent experiments supporting a role of translocation ratchets in the secretion and import of proteins and DNA. (shrink)

This paper examines the social and organizational innovation processes undertaken by small-scale producers engaged in short food supply chains in the North Swedish region of Västerbotten. The study uses the notion of proximity to empirically analyse and conceptually explore these phenomena. The paper illustrates the ‘new associationalism’ mobilized by producers in order to promote knowledge exchange and learning and highlights the role of translocal practices in sustaining this transition. The study found that open and trusted interactions with consumers are central (...) to the development of ‘quasi-organic’ practices, and that producers belong to numerous motley associations of food professionals facilitating the creation of collective meanings about near-produced quality food. The paper contributes to the rapprochement between agri-food studies and human geography to understand the formation of local food systems from an evolutionary and relational perspective. (shrink)

Protein translocation across biological membranes is of fundamental importance for the biogenesis of organelles and in protein secretion. We will give an overview of the recent achievements in the understanding of protein translocation across mitochondrial membranes(1‐5). In particular we will focus on recently identified components of the mitochondrial import apparatus.

Recent research on agricultural innovation has outlined social networks’ role in diffusing agricultural knowledge; however, so far, it has broadly neglected the socio-spatial dimensions of innovation processes. Against this backdrop, we apply a spatially explicit translocal network perspective in order to investigate the role of migration-related translocal networks for adaptive change in a small-scale farming community in Northeast Thailand. By means of formal social network analysis we map the socio-spatial patterns of advice sharing regarding changes in sugarcane and rice farming (...) over a period of five years. We find that, in translocally connected and mobile rural communities, a substantial share of advice originates from translocal levels. Translocal advice is dominantly provided through weak and formal ties with extension agencies and shared by few highly central larger-scale farmers within sparse local networks. This draws the picture of top-down translocal innovation flows driven by extension agencies and brokered through elite farmers. A closer look on institutional context and key actors of particular changes, however, suggests the potential of migration-related translocal networks and migration experience in fostering bottom-up innovations. Migration-related innovations transfers can promote adaptive capacity also among less favorably connected actors, especially if changes are geared towards limited household resources and are compatible with social practices of small-scale farming. We conclude that a translocal network perspective is instructive for research and extension interested in leveraging more inclusive agricultural innovation. (shrink)

Recent studies indicate that mammalian chromosomes contain discretecis‐acting loci that control replication timing, mitotic condensation, and stability of entire chromosomes. Disruption of the large non‐coding RNA gene ASAR6 results in late replication, an under‐condensed appearance during mitosis, and structural instability of human chromosome 6. Similarly, disruption of the mouse Xist gene in adult somatic cells results in a late replication and instability phenotype on the X chromosome. ASAR6 shares many characteristics with Xist, including random mono‐allelic expression and asynchronous (...) replication timing. Additional “chromosome engineering” studies indicate that certain chromosome rearrangements affecting many different chromosomes display this abnormal replication and instability phenotype. These observations suggest that all mammalian chromosomes contain “inactivation/stability centers” that control proper replication, condensation, and stability of individual chromosomes. Therefore, mammalian chromosomes contain four types ofcis‐acting elements, origins, telomeres, centromeres, and “inactivation/stability centers”, all functioning to ensure proper replication, condensation, segregation, and stability of individual chromosomes. (shrink)

In this paper, we hypothesize that X chromosome-associated mechanisms, which affect X-linked genes and are behind the immunological advantage of females, may also affect X-linked microRNAs. The human X chromosome contains 10% of all microRNAs detected so far in the human genome. Although the role of most of them has not yet been described, several X chromosome-located microRNAs have important functions in immunity and cancer. We therefore provide a detailed map of all described microRNAs located on human and mouse X (...) chromosomes, and highlight the ones involved in immune functions and oncogenesis. The unique mode of inheritance of the X chromosome is ultimately the cause of the immune disadvantage of males and the enhanced survival of females following immunological challenges. How these aspects influence X-linked microRNAs will be a challenge for researchers in the coming years, not only from an evolutionary point of view, but also from the perspective of disease etiology. (shrink)

X‐chromosome inactivation refers to the coordinate regulation of almost all genes on the mammalian × chromosome. Most models for × chromosome inactivation suppose a role for methylation of × chromosome DNA sequences and/or the heterochromatinization of large «domains» of the × chromosome containing many genes.1 Some recent work concerning the expression of X‐linked transgenes, and parallels between regulated expression of sex‐linked genes in invertebrates and mammals, suggest that × chromosome inactivation may be a gene‐by‐gene event mediated by the interaction between (...) regulatory sequences common to all X‐linked genes and soluble activators and repressors. (shrink)

Cracks in the one‐gene, one‐band paradigm for polytene chromosome organization are widening. At the same time evidence is accumulating suggesting that decondensed regions of the chromosomes (puffs, diffuse bands, interbands and possibly vacuoles within some bands) are generally associated with gene transcription. A model, now on the ascendancy, is based on the proposal that the band‐interband pattern is primarily a reflection of local transcriptional state, rather than the distribution of genic and non‐genic material.

Extraordinary extended lampbrush chromosomes with thousands of transcription loops are favorable objects in chromosome biology. Chromosomes become lampbrushy due to unusually high rate of transcription during oogenesis. However, until recently, the information on the spectrum of transcribed sequences as well as genomic context of individual chromomeres was mainly limited to tandemly repetitive elements. Here we briefly outline novel findings and future directions in lampbrush chromosome studies in the post‐genomic era. We emphasize the fruitfulness of combining genome‐wide approaches with (...) microscopy imaging techniques using lampbrush chromosomes as a remarkable model object. We believe that new data on the spectrum of sequences transcribed on the lateral loops of lampbrush chromosomes and their structural organization push the boundaries in the discussion of their biological role. Also see the video abstract here: https://youtu.be/zexoHfzX9rM. (shrink)

Transport through the nuclear pore complex (NPC), a keystone of the eukaryotic building plan, is known to involve a large channel and an abundance of phenylalanine–glycine (FG) protein domains serving as binding sites for soluble nuclear transport receptors and their cargo complexes. However, the conformation of the FG domains in vivo, their arrangement in relation to the transport channel and their function(s) in transport are still vividly debated. Here, we revisit a number of representative transport models—specifically Brownian affinity gating, selective (...) phase gating, reversible FG domain collapse, and reduction of dimensionality (ROD)—in the light of new data obtained by optical single transporter recording, optical superresolution microscopy, artificial nanopores, and many other techniques. The analysis suggests that a properly adapted, simplified version of the ROD model accounts well for the available data. This has implications for nucleocytoplasmic transport in general. (shrink)

Here we discuss a “chromosome separation checkpoint” that might regulate the anaphase‐telophase transition. The concept of cell cycle checkpoints was originally proposed to account for extrinsic control mechanisms that ensure the order of cell cycle events. Several checkpoints have been shown to regulate major cell cycle transitions, namely at G1‐S and G2‐M. At the onset of mitosis, the prophase‐prometaphase transition is controlled by several potential checkpoints, including the antephase checkpoint, while the spindle assembly checkpoint guards the metaphase‐anaphase transition. Our hypothesis (...) is based on the recently uncovered feedback control mechanism that delays chromosome decondensation and nuclear envelope reassembly until effective separation of sister chromatids during anaphase is achieved. A central player in this potential checkpoint is the establishment of a constitutive, midzone‐based Aurora B phosphorylation gradient that monitors the position of chromosomes along the spindle axis. We propose that this surveillance mechanism represents an additional step towards ensuring mitotic fidelity. (shrink)

In Caenorhabditis elegans, sex is determined by the number of X chromosomes which, in turn, determines the expression of the X‐linked gene xol‐1. Recent work(1) has shown that xol‐1 expression is controlled by least two distinct regulatory mechanisms, one transcriptional and another post‐transcriptional. The transcriptional regulator is a repressor acting in XX embryos; although the specific gene has not been identified, the chromosome region has been defined. A previously defined regulator of xol‐1, known as fox‐1, maps to a different (...) region of the X chromosome and works post‐transcriptionally, consistent with the identification of the fox‐1 gene product as a putative RNA binding protein(2). (shrink)

With the new and highly accurate noninvasive prenatal test, new options for screening become available. I contend that the current state of the art of NIPT is already in need of a thorough ethical investigation and that there are different points to consider before any chromosomal or subchromosomal condition is added to the screening panel of a publicly funded screening program. Moreover, the application of certain ethical principles makes the inclusion of some conditions unethical in a privately funded scheme, even (...) if such screening would enhance a woman’s reproductive autonomy. On the one hand, a screening program aimed solely at the detection of Down syndrome is subject to the technological imperative and should be reassessed in the light of technologies that allow for the detection of conditions that are at least as severe. On the other hand, some chromosomal conditions should not be included in any screening programs, because this would violate certain ethical principles, such as the right of the future child to genetic privacy. (shrink)

Mammal sex determination depends on an XY chromosome system, a gene for testis development and a means of activating the X chromosome. The duckbill platypus challenges these dogmas.1,2 Gutzner et al.1 find no recognizable SRY sequence and question whether the mammalian X was even the original sex chromosome in the platypus. Instead they suggest that the original platypus sex chromosomes were derived from the ZW chromosome system of birds and reptiles. Unraveling the puzzles of sex determination and dosage compensation (...) in the platypus has been complicated by the fact that it has a surplus of sex chromosomes. Rather than a single X and Y chromosome, the male platypus has five Xs and five Ys. BioEssays 27:681–684, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

The structures of specific chromosome regions, centromeres and telomeres, present a number of puzzles. As functions performed by these regions are ubiquitous and essential, their DNA, proteins and chromatin structure are expected to be conserved. Recent studies of centromeric DNA from human, Drosophila and plant species have demonstrated that a hidden universal centromere‐specific sequence is highly unlikely. The DNA of telomeres is more conserved consisting of a tandemly repeated 6–8 bp Arabidopsis‐like sequence in a majority of organisms as diverse as (...) protozoan, fungi, mammals and plants. However, there are alternatives to short DNA repeats at the ends of chromosomes and for telomere elongation by telomerase. Here we focus on the similarities and diversity that exist among the structural elements, DNA sequences and proteins, that make up terminal domains (telomeres and subtelomeres), and how organisms use these in different ways to fulfil the functions of end‐replication and end‐protection. BioEssays 27:685–697, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

Hibakusha are “witnesses” of the atomic bombings, not just in a standard sense but also in the instrumental sense. For medical and scientific experts, hibakusha are biological resources of unparalleled scientific value. Over the past seventy years, the hibakusha bodies have narrated what it means to be exposed to radiation. In this paper, I explore studies at the Atomic Bomb Casualty Commission that examined hibakusha bodies as sites where risk could be read. I focus on a period from the mid-1950s (...) to 1975, during which new methods, practices, and technologies allowed ABCC scientists to investigate chromosomes as a way to study radiation exposure and human risk. By focusing on chromosomal aberrations, ABCC scientists connected their work directly to the emerging infrastructure for radiobiology at the time. ABCC administrators actively sought out such prestige, especially given their relationship with the Atomic Energy Commission. The shift in approach would also alleviate some public relations problems with which the institution was struggling. Launching a cytogenetics program required some older practices that had assumed American privilege and dominance to be abandoned. Eventually, the decision to let chromosomes speak of radiation exposure brought about fundamental changes in ABCC, which came to symbolize the model for future studies at the organization, especially as ABCC was transitioning to a US-Japan binational organization. More broadly, this case highlights the intricate scientific negotiation of radiation risk where uncertainties necessarily prevail. (shrink)

What we consider “nature” is always historical and relational, shaped in contingent configurations of representational and social practices. In the early twentieth century, the English ecologist A.G. Tansley lamented the pervasive problem of international misunderstandings concerning the nature of “nature.” In order to create some consensus on the concepts and language of ecological plant geography, Tansley founded the International Phytogeographical Excursion, which brought together leading plant geographers and botanists from North America and Europe. The first IPE in August 1911 started (...) with the Norfolk Broads. It was led by Marietta Pallis, Tansley’s former student at Cambridge. This trip and the work of Pallis, neglected in other accounts of this early period of the history of ecology, influenced the relations between Tansley and important American ecologists H.C. Cowles and F.E. Clements. Understanding “place” as a network of relations, our regional focus shows how taking international dialogue, travel and interchange into account enriches understanding of ecological practice. (shrink)

Chromosomes that harbor dominant sex determination loci are predicted to erode over time—losing genes, accumulating transposable elements, degenerating into a functional wasteland and ultimately becoming extinct. The Drosophila melanogaster Y chromosome is fairly far along this path to oblivion. The few genes on largely heterochromatic Y chromosome are required for spermatocyte‐specific functions, but have no role in other tissues. Surprisingly, a recent paper shows that divergent Y chromosomes can substantially influence gene expression throughout the D. melanogaster genome.1 These (...) results show that variation on Y has an important influence on the deployment of the genome. BioEssays 30:409–411, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Sex chromosomes are advantageous to mammals, allowing them to adopt a genetic rather than environmental sex determination system. However, sex chromosome evolution also carries a burden, because it results in an imbalance in gene dosage between females (XX) and males (XY). This imbalance is resolved by X dosage compensation, which comprises both X chromosome inactivation and X chromosome upregulation. X dosage compensation has been well characterized in the soma, but not in the germ line. Germ cells face a special (...) challenge, because genome wide reprogramming erases epigenetic marks responsible for maintaining the X dosage compensated state. Here we explain how evolution has influenced the gene content and germ line specialization of the mammalian sex chromosomes. We discuss new research uncovering unusual X dosage compensation states in germ cells, which we postulate influence sexual dimorphisms in germ line development and cause infertility in individuals with sex chromosome aneuploidy. (shrink)

X chromosome inactivation (XCI) is an essential epigenetic process that ensures X‐linked gene dosage equilibrium between sexes in mammals. XCI is dynamically regulated during development in a manner that is intimately linked to differentiation. Numerous studies, which we review here, have explored the dynamics of X inactivation and reactivation in the context of development, differentiation and diseases, and the phenotypic and molecular link between the inactive status, and the cellular context. Here, we also assess whether XCI is a uniform mechanism (...) in mammals by analyzing epigenetic signatures of the inactive X (Xi) in different species and cellular contexts. It appears that the timing of XCI and the epigenetic signature of the inactive X greatly vary between species. Surprisingly, even within a given species, various Xi configurations are found across cellular states. We discuss possible mechanisms underlying these variations, and how they might influence the fate of the Xi. (shrink)

From island biogeography theory, the ethic of organic diversity was posited as a precept to guide applied biogeography. It states that humanity must act in such a way as to reduce the rate of worldwide species extinction for an indefinite period of time. Almost 50 years later, the ethic of organic diversity remains relevant in the context of the debate over species translocation practices. Ultimately, matters of biodiversity conservation are too complex to expect an exceptionless moral framework to determine (...) whether species translocation is acceptable in every situation. Instead, individual cases should be judged based on the adequacy of their decision-making processes. (shrink)

Mammals have a very complex, tightly controlled, and developmentally regulated process of dosage compensation. One form of the process equalizes expression of the X‐linked genes, present as a single copy in males (XY) and as two copies in females (XX), by inactivation of one of the two X‐chromosomes in females. The second form of the process leads to balanced expression between the X‐linked and autosomal genes by transcriptional upregulation of the active X in males and females. However, not all (...) X‐linked genes are absolutely balanced. This review is focused on the recent advances in studying the dosage compensation phenomenon in mammals. (shrink)