In lieu of an abstract, here is a brief excerpt of the content:Books ReceivedThe Ambitions of Curiosity: Understanding the World in Ancient Greece and China. By G.E.R. Lloyd. Cambridge: Cambridge University Press, 2002. Pp. xvi + 175. Price not given.The Art of the Han Essay: Wang Fu's Ch'ien-Fu Lun. By Anne Behnke Kinney. Tempe: Center for Asian Studies, Arizona State University, 1990. Pp. xi + 154. Paper $10.00.The Autobiography of Jamgön Kongtrul: A Gem of Many Colors. By Jamgön Kongtrul Lodrön (...) Thayé and translated by Richard Barron (Chökyi Nyima). Ithaca, New York: Snow Lion Publications, 2003. Pp. xxii + 549. Price not given.Awesome Nightfall: The Life, Times, and Poetry of Saigyō. By William R. LaFleur. Boston: Wisdom Publications, 2003. Pp. xiii + 173. Paper $14.95.Becoming the Compassion Buddha: Tantric Mahamudra for Everyday Life. By Lama Thubten Yeshe, edited by Robina Courtin, and foreword by Geshe Lhundub Sopa. Boston: Wisdom Publications, 2003. Pp. xi + 194. Paper $14.95.Between Two Worlds East and West: An Autobiography. By J. N. Mohanty. New Delhi: Oxford University Press, 2002. Pp. ix + 134. Hardcover RS 525.00.The Chinese Face of Jesus Christ. Edited by Roman Malek, S.V.D. Sankt Augustin, Germany: Institut Monumenta Serica and China-Zentrum; and Nettetal, Germany: Steyler Verlag, 2002. Pp. 391. EUR 40.00.Chinese Medicine in Contemporary China: Plurality and Synthesis. By Volker Scheid. Durham and London: Duke University Press, 2002. Pp. xiv + 407. Hardcover $69.95. Paper $23.95.Confucian Feminist: Memoirs of Zeng Baosun (1893-1978). Translated and adapted by Thomas L. Kennedy. Philadelphia: American Philosophical Society, 2002. Pp. xxi + 170. Price not given.Consciousness Studies: Cross-Cultural Perspectives. By K. Ramakrishna Rao. Jefferson (North Carolina) and London: McFarland and Company, 2002. Pp. 367. Hardcover $65.00.Constituting Communities: Theravāda Buddhism and the Religious Cultures of South and Southeast Asia. Edited by John Clifford Holt, Jacob N. Kinnard, and Jonathan S. Walters. Albany: State University of New York Press, 2003. Pp. viii + 224. Hardcover $65.50. Paper $21.95.Developments in Indian Philosophy from Eighteenth Century Onwards: Classical and Western. By Daya Krishna. Volume X Part 1 of History of Science, Philosophy and Culture in Indian Civilization, edited by D. P. Chattopadhyaya. New [End Page 110] Delhi: Centre for Studies in Civilizations, 2001. Pp. xxiii + 417. Hardcover RS 1200.East and West: Identità e dialogo interculturale. By Giangiorgio Pasqualotto. Venezia: Marsilo Editori, 2003. Pp. 210. EUR 16.00.Effortless Action: Wu-wei as Conceptual Metaphor and Spiritual Ideal in Early China. By Edward Slingerland. New York: Oxford University Press, 2003. Pp. xii + 352. Price not given.Encountering Kā lī: In the Margins, at the Center, in the West. Edited by Rachel Fell McDermott and Jeffrey J. Kripal. Berkeley and Los Angeles: University of California Press, 2003. Pp. xviii + 321. Hardcover $55.00, £37.95. Paper $21.95, £15.95.Encyclopedia of Chinese Philosophy. Edited by Antonio S. Cua. New York and London: Routledge, 2003. Pp. xx + 1020. Hardcover $150.00.Essays on Indian Philosophy. By J. N. Mohanty and edited by Purushottama Bilimoria. New Delhi: Oxford University Press, 2002. Pp. xxxvii + 347. Paper RS 525.00.Faith, Humor, and Paradox. By Ignacio L. Götz. Westport, Connecticut: Praeger Publishers, 2002. Pp. 136. Hardcover $61.95.Four Illusions: Candrakīrti's Advice for Travelers on the Bodhisattva Path. Translated by Karen C. Lang. New York: Oxford University Press, 2003. Pp. xv + 240. Price not given.The Great Awakening: A Buddhist Social Theory. By David R. Loy. Boston: Wisdom Publications, 2003. Pp. 223. Paper $16.95.The Hidden History of The Tibetan Book of the Dead. By Bryan J. Cuevas. New York: Oxford University Press, 2003. Pp. xi + 328. Price not given.Huang Di nei jing su wen: Nature, Knowledge, Imagery in an Ancient Chinese Medical Text. By Paul U. Unschuld. Berkeley and Los Angeles: University of California Press, 2003. Pp. xii + 520. Hardcover $75.00, £52.00.In Dewey's Wake: Unfinished Work of Pragmatic Reconstruction. Edited by William J. Gavin. Albany: State University of New York Press, 2003. Pp. vi + 249. Hardcover $71.50. Paper $23.95.Knowledge and Freedom in Indian Philosophy. By Tara Chatterjea. Lanham, Maryland: Lexington Books, 2002. Pp. xvi + 159. Hardcover... (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)

This article serves as a demonstration of how certain models of literary analysis, used to theorize and analyze fiction and narrative, can also be applied to scientific communication in such a manner as to promote the accessibility of science to the general public and a greater awareness of the methodology used in making scientific discovery. The approach of this article is based on the assumption that the principles of structuralism and semiotics can provide plausible explanations for the divide between the (...) reception of science and literature. We provide a semiotic analysis of a scientific article that has had significant impact in the field of molecular biology with profound medical implications. Furthermore, we show how the structural and semiotic characteristics of literary texts are also evident in the scientific papers, and we address how these characteristics can be applied to scientific prose in order to propose a model of scientific communication that reaches the public. By applying this theoretical framework to the analysis of both scientific and literary communication, we establish parallels between primary scientific texts and literary prose. (shrink)

Hameroff: I became interested in understanding consciousness as an undergraduate at the University of Pittsburgh in the late 60's. In my third year of medical school at Hahnemann in Philadelphia I did a research elective in professor Ben Kahn's hematology-oncology lab. They were studying various types of malignant blood cells, and I became interested in mitosis-looking under the microscope at normal and abnormal cell division. I became fascinated by centrioles and mitotic spindles pulling apart the chromosomes, doing this little (...) dance, dividing the cytoplasm, establishing the daughter-cell architecture, and beginning differentiation. I remember wondering to myself how these centrioles and mitotic spindles "knew" where to go and what to do. What kind of intelligence was running the show at the cellular level? (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)

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)

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)

Recent studies indicate that mammalian chromosomes contain discrete cis‐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 of cis‐acting elements, origins, telomeres, centromeres, and “inactivation/stability centers”, all functioning to ensure proper replication, condensation, segregation, and stability of individual chromosomes. (shrink)

A total of 944 expressed sequence tags generated 2212 EST loci mapped to homoeologous group 1 chromosomes in hexaploid wheat. EST deletion maps and the consensus map of group 1 chromosomes were constructed to show EST distribution. EST loci were unevenly distributed among chromosomes 1A, 1B, and ID with 660, 826, and 726, respectively. The number of EST loci was greater on the long arms than on the short arms for all three chromosomes. The distribution of ESTs along chromosome (...) arms was nonrandom with EST clusters occurring in the distal regions of short arms and middle regions of long arms. Duplications of group 1 ESTs in other homoeologous groups occurred at a rate of 35.5%. Seventy-five percent of wheat chromosome 1 ESTs had significant matches with rice sequences, where large regions of conservation occurred between wheat consensus chromosome 1 and rice chromosome 5 and between the proximal portion of the long arm of wheat consensus chromosome 1 and rice chromosome 10. Only 9.5% of group 1 ESTs showed significant matches to Arabidopsis genome sequences. The results presented are useful for gene mapping and evolutionary and comparative genomics of grasses. (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)

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)

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)

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)

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)

Supernumerary B chromosomes are dispensable elements of the genome which can be retained in populations at high frequencies, despite being deleterious, through the ability to undergo non‐Mendelian inheritance. Their mode of origin is, however, obscure. Recent work on gynogenetic fish has demonstrated the incorporation of small, unstable, centromere‐containing microchromosomes, probably of interspecific derivation, into an asexual lineage(1). That these resemble B chromosomes both in structure and behaviour is consistent with the proposal that hybridisation between closely related species may be a (...) significant mode of origin for such selfish genetic elements. Additional work on the B chromosome of a parasitoid wasp and observations on patterns of chromosome breakage from somatic cell hybrids also support this hypothesis. (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)

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)

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)

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 (...) 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)

Mammalian sex chromosomes exhibit marked sexual dimorphism in behavior during gametogenesis. During oogenesis, the X chromosomes pair and participate in unrestricted recombination; both are transcriptionally active. However, during spermatogenesis the X and Y chromosomes experience spatial restriction of pairing and recombination, are transcriptionally inactive, and form a chromatin domain that is markedly different from that of the autosomes. Thus the male germ cell has to contend with the potential loss of X‐encoded gene products, and it appears that coping strategies have (...) evolved. Genetic control of sex‐chromosome inactivation during spermatogenesis does not involve pairing or the presence of the Y chromosome or an intact X chromosome, and may therefore be under exogenous control by the gonad. Sex‐chromosome reactivation during oogenesis and inactivation during spermatogenesis probably reflect specific meiotic events such as recombination. Understanding these phenomena may help explain other sex‐related differences in genetic recombination. (shrink)

Detection of genetic aberrations in prenatal samples, obtained through amniocentesis or chorion villus biopsy, is increasingly performed using chromosomal microarray, a technique that can uncover both aneuploidies and copy number variants throughout the genome. Despite the obvious benefits of CMA, the decision on implementing the technology is complicated by ethical issues concerning variant interpretation and reporting. In Belgium, uniform guidelines were composed and a shared database for prenatal CMA findings was established. This Belgian approach sparks discussion: it is evidence-based, prevents (...) inconsistencies and avoids parental anxiety, but can be considered paternalistic. Here, we reflect on the cultural and moral bases of the Belgian reporting system of prenatally detected variants. (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)

Small tandem DNA duplications in the range of 15 to 300 base‐pairs play an important role in the aetiology of human disease and contribute to genome diversity. Here, we discuss different proposed mechanisms for their occurrence and argue that this type of structural variation mainly results from mutagenic repair of chromosomal breaks. This hypothesis is supported by both bioinformatical analysis of insertions occurring in the genome of different species and disease alleles, as well as by CRISPR/Cas9‐based experimental data from different (...) model systems. Recent work points to fill‐in synthesis at double‐stranded DNA breaks with complementary sequences, regulated by end‐joining mechanisms, to account for small tandem duplications. We will review the prevalence of small tandem duplications in the population, and we will speculate on the potential sources of DNA damage that could give rise to this mutational signature. With the development of novel algorithms to analyse sequencing data, small tandem duplications are now more frequently detected in the human genome and identified as oncogenic gain‐of‐function mutations. Understanding their origin could lead to optimized treatment regimens to prevent therapy‐induced activation of oncogenes and might expose novel vulnerabilities in cancer. (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)

Early in the 20th century Bateson, Doncaster and Punnett formed a cooperative collective to share research findings on the chromosome theory of heredity (CTH). They cross-bred plants and animals to correlate behaviour of chromosomes and heredity of individual traits. Doncaster was the most enthusiastic proponent of the new theory and worked for years to convince Bateson and Punnett on its relevance to their own research. The two younger biologists collaborated with Bateson, the preeminent geneticist in England. As their own (...) reputations developed, their research findings allied with the consensus on the importance of the CTH by the broader scientific community. After Doncaster’s tragic death in 1920, major objections to the theory had been resolved; Bateson and Punnett then utilized the CTH to construct chromosome maps detailing locations of specific genes on particular chromosomes in several different species. The marriage of heredity and cytology enhanced confidence that the theory was an accurate mechanism to explain inheritance in both plants and animals. (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)

Replication of the main chromosome in the halophilic archaeon Haloferax volcanii was recently reported to continue despite deletion of all active replication origins. Equally surprising, the deletion strain grew faster than the parent strain. It was proposed that origin‐less H. volcanii duplicate their chromosomes via recombination‐dependent replication. Here, we recall our present knowledge of this mode of chromosome replication in different organisms. We consider the likelihood that it accounts for the viability of H. volcanii deleted for its main (...) specific replication origins, as well as possible alternative interpretations of the results. The selective advantages of having defined chromosome replication origins are discussed from a functional and evolutionary perspective. (shrink)

Mechanisms involved in the regulation of development and its genetic control are receiving ever‐increasing attention in studies of mammalian developmental genetics. The potential success of such studies is strongly enhanced by the availability of suitable systems of analysis. Such a system was identified in a series of radiation‐induced chromosomal deletions at and around the albino (c) locus of the mouse associated with cell type‐specific effects on liver differentiation. Their detailed study has aided the analysis of possible machanisms of cell type‐specific (...) gene expression. As summarized in this review, the experimental results strongly suggest that specific trans‐acting developmental regulatory genes are concerned with the differentiation of hormone‐inducible expression of a cluster of hepatocyte specific structural genes mapping in different parts of the genome. (shrink)

Telomeres are protective caps for chromosome ends that are essential for genome stability. Broken chromosomes missing a telomere will not be maintained unless the chromosome is ‘healed’ with the formation of a new telomere. Chromosome healing can be a programmed event following developmentally regulated chromosome fragmentation, or it may occur spontaneously when a chromosome is accidentally broken. In this article we discuss the consequences of telomere loss and the possible mechanisms that the enzyme telomerase employs (...) to form telomeres de novo on broken chromosome ends. (shrink)

Despite its widespread existence, the adaptive role of aneuploidy (the abnormal state of having an unequal number of different chromosomes) has been a subject of debate. Cellular aneuploidy has been associated with enhanced resistance to stress, whereas on the organismal level it is detrimental to multicellular species. Certain aneuploid karyotypes are deleterious for specific environments, but karyotype diversity in a population potentiates adaptive evolution. To reconcile these paradoxical observations, this review distinguishes the role of aneuploidy in cellular versus organismal evolution. (...) Further, it proposes a population genetics perspective to examine the behavior of aneuploidy on a populational versus individual level. By altering the copy number of a significant portion of the genome, aneuploidy introduces large phenotypic leaps that enable small cell populations to explore a wide phenotypic landscape, from which adaptive traits can be selected. The production of chromosome number variation can be further increased by stress‐ or mutation‐induced chromosomal instability, fueling rapid cellular adaptation. (shrink)

A combination of cytogenetic and molecular analyses has shown that several different transposable elements are involved in the restructuring of Drosophila chromosomes. Two kinds of elements, P and hobo, are especially prone to induce chromosome rearrangements. The mechanistic details of this process are unclear, but, at least some of the time, it seems to involve ectopic recombination between elements inserted at different chromosomal sites; the available data suggest that these ectopic recombination events are much more likely to occure between (...) elements in the same chromosome than between elements in different chromosomes. Other Drosophila transposons also appear to mediate chromosome restructuring by ectopic recombination; these include the retrotransposons BEL, roo, Docand I and the foldback element FB. In addition, two retrotransposons, HeT‐A and TART, have been found to be associated specifically with the ends of Drosophila chromosomes. Very limited data indicate that transposon‐mediated chromosome restructuring is occurring in natural populations of Drosophila. This suggests that transposable elements may help to shape the structure of the Drosophila genome and implies that they may have a similar role in other organisms. (shrink)

With the assumption of inactivation of small traits in bacteriophages “chromosomes” by ultraviolet irradiation the probability of multiplicity reactivation of irradiated phages is calculated. The result appears to be in agreement with the experimental results ofDulbecco.In the mathematical treatment of the problem a distinction is made between ordinary genes, with probability of inactivation negligible relative to the probability of inactivation of the whole phage, and a few vulnerable centers or genes whose probability of inactivation is not negligible. The hypothesis of (...) the existence of vulnerable centers appears necessary in order to explainDulbecco's experimental results.Postulant que de petites sections des „chromosomes” du bactériophage sont inactivés par l'irradiation ultraviolette, on a calculé la probabilité de réactivation par infection multiple des bactériophages traités par les rayons ultraviolets. Les résultats obtenus s'accordent avec les résultats expérimentaux de M.Dulbecco.Dans la tractation mathématique des problèmes une distinction a été faite entre les gènes ordinaires — dont la probabilité d'inactivation prise individuellement peut Être négligée relativement à la probabilité d'inactivation du phage entier — et quelques centres vulnérables ou gènes dont la probabilité d'inactivation ne pourrait Être négligée.L'hypothèse de l'existance des centres vulnérables s'est démontrée nécessaire à l'explication des résultats expérimentaux de M.Dulbecco.Die Wahrscheinlichkeit der Reaktivation durch multiplen Infektionen ist unter Voraussetzung, dass die Ultraviolett-Bestrahlung kleine Teile der Bakteriophagenchromosomen inaktiviert, berechnet. Das Ergebnis entspricht den experimentellen ResultatenDulbecco's.In der mathematischen Behandlung des Problems ist ein Unterschied gemacht worden zwischen gewöhnlichen Genen — wovon jeder eine geringe Wahrscheinlichkeit der Inaktivierung hat, in Bezug auf die Wahrscheinlichkeit der Inaktivierung der ganzen Bakteriophage — und einige verletzbare Stellen oder Genen, wovon die Wahrscheinlichkeit der Inaktivierung grössenordnungsmÄssig höher liegt. Die Hypothese über die verletzbaren Stellen war notwendig um die experimentellen ResultateDulbecco's zu erklÄren. (shrink)

We discuss here a series of testable hypotheses concerning the role of chromosome folding into topologically associating domains (TADs). Several lines of evidence suggest that segmental packaging of chromosomal neighborhoods may underlie features of chromatin that span large domains, such as heterochromatin blocks, association with the nuclear lamina and replication timing. By defining which DNA elements preferentially contact each other, the segmentation of chromosomes into TADs may also underlie many properties of long‐range transcriptional regulation. Several observations suggest that TADs (...) can indeed provide a structural basis to regulatory landscapes, by controlling enhancer sharing and allocation. We also discuss how TADs may shape the evolution of chromosomes, by causing maintenance of synteny over large chromosomal segments. Finally we suggest a series of experiments to challenge these ideas and provide concrete examples illustrating how they could be practically applied. (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)

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)

The chromocenter of Drosophila polytene chromosomes, which consists of two major chromatin types, has long been a troublesome region in molecular terms. The recent microcloning of part of this region, the isolation of a monoclonal antibody to a beta‐heterochromatin binding protein, and new in situ studies now shed a little more light on this chromosomal region.

A complex structure, visible by electron microscopy, surrounds each chromosome during mitosis. The organization of this structure is distinct from that of the chromosomes and the cytoplasm. It forms a perichromosomal layer that can be isolated together with the chromosomes. This layer covers the chromosomes except in centromeric regions. The perichromosomal layer includes nuclear and nucleolar proteins as well as ribonucleoproteins (RNPs). The list of proteins and RNAs identified includes nuclear matrix proteins (perichromin, peripherin), nucleolar proteins (perichro‐monucleolin, Ki‐67 antigen, (...) B23 protein, fibrillarin, p103, p52), ribosomal proteins (S1) and snRNAs (U3 RNAs). Only limited information is available about how and when the perichromosomal layer is formed. During early prophase, the proteins extend from the nucleoli towards the periphery of the nucleus. Thin cordon‐like structures reach the nuclear envelope delimiting areas in which chromosomes condense. At telophase, the proteins are associated with the part of the chromosomes remaining condensed and accumulate in newly formed nucleoli in regions where chromatin is already decondensed. The perichromosomal layer contains several different classes of proteins and RNPs and it has been attributed various roles: (1) in chromosome organization, (2) as a barrier around the chromosomes, (3) involvement in compartmentation of the cells in prophase and telophase and (4) a binding site for chromosomal passenger proteins necessary to the early process of nuclear assembly. (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.

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)

Photographs document the growth of Philadelphia and show the life of its citizens prior to World War II.

We may now ask the question: In what historical perspective should we place the work of Richard Goldschmidt? There is no doubt that in the period 1910–1950 Goldschmidt was an important and prolific figure in the history of biology in general, and of genetics in particular. His textbook on physiological genetics, published in 1938, was an amazing compendium of ideas put forward in the previous half-century about how genes influence physiology and development. His earlier studies on the genetic and geographic (...) distribution of the various species and races of Lymantria contributed soundly to an understanding of the inheritance and development of sex, as well as the genetics of speciation. He was a curious mixture of the experimentalist, empiricist, and theorizer, who could grasp both the large and the small at once and wrap them into the same integrated and coherent package.In insisting on trying to relate genetics to development, Goldschmidt was continually forced to speculate and to forsake experimental fact for generalized theory. In refusing to reconcile a physiological and developmental conception with a corpuscular theory of the gene, he forced himself to substitute for a large body of experimentally verified evidence, vague and general speculations which did not lead in any precise direction. L. C. Dunn summarizes succinctly the effect of Goldschmidt's thinking on the development of genetic theory: Although Goldschmidt's ideas had a considerable influence in directing attention to the developmental processes intervening between genes and characters, they did not lead to the establishment of a general theory of development in genetical terms. In fact, at the end of the period, as signalized by Goldschmidt's book of 1938 [Physiological Gentics] doubt remained whether there was a field with a defined problem which could be identified as developmental genetics.Yet the frequency with which Goldschmidt is cited by later writers suggests that there is a more positive side to his contribution than this. The early Mendelians had recognized the genic constitution of organisms and the Drosophila workers had uncovered in detail the chromosomal mechanism of heredity. These great discoveries were of classical character, solidly based on a multitude of well established facts. By themselves, however, they would not have been sufficient to place genetics in the central position within biology which it was to assume. Beyond the “static” analysis of gene transmission an insight was needed into the dynamic role of genes in cellular physiology, biochemistry, and development. Goldschmidt recognized this aspect and outlined in brilliant generalizations a physiological theory of genetics. Necessarily the prophetic nature of this achievement — romantic in the sense of Ostwald's classification of great scientists and their discoveries — transcended its factual basis. It was the audacity of the theoretician unimpeded by the still scanty data which gave a new focus to biological thought.Some have called Goldschmidt an “obstructionist” in the history of genetics—one whose efforts were largely directed toward useless and continual criticism — challenge for the sake of challenge. As this line of argument goes, time wasted answering Goldschmidt's poorly conceived criticisms could have been better used to pursue new lines of thought within the classical gene theory. Sometimes historians are upbraided for studying the work of such “obstructionists,” or even the work of those whose ideas have later proved to be inadequate. This argument misses the point of history and the lessons which it can teach. Perhaps Goldschmidt did take the time of a number of the classical geneticists who tried to answer his objections to the gene theory; and perhaps many of his own ideas about genes were, by today's view, “wrong.” These are always easier judgments to make by hindsight than at the moment. But that is not the point. Goldschmidt had a considerable influence on his contemporaries, and to dismiss him as an obstructionist because his opponents later proved to be more nearly right, distorts history and obscures significant questions which we might well be asking. It might be valuable to know why Goldschmidt felt compelled to be an iconoclast —and how that impulse, psychological in orgin, led him to overlook critical items of evidence which his opponents considered more carefully. It might also be valuable to try and understand how a contemporary of Goldschmidt or. Morgan really viewed the gene theory — what were its strong and weak point? Such questions are not readily answered by studying the work of only those men who were correct by later standards.Answers to some of the above questions can be gleaned from this study of Goldschmidt — though the first, and most psychologically oriented, question is largely untouched here.On the one hand, Goldschmidt forced classical geneticists to reexamine the foundation of their ideas about the nature, inviolability, and even physical dimensions of genes. He also kept alive the very real problems of gene physiology and its relations to development — a relationship that was given less attention by the Drosophila school in their pursuit of the transmission process. On a broader level he emphasized to the biological community a principle that was in danger of being lost in the enthusiasm surrounding the expansion of the Mendelian-chromosome theory. The point was that all theories in science are transient, logical constructs which should not be held as sacred. Time and again, as the history of science has shown, theories become rigid structures which retard new modes of thought. From Goldschmidt's perspective, the gene theory was in danger of performing just that function, for it was preventing workers from viewing the gene in a functional as well as a structural light.On the other hand, examining the work of critics (or even of outright “obstructionists”) gives the historian an opportunity to observe how the more established community of scholars at some point in time reacts to challenges of its cherished ideas. The fact that many workers in his own day (such as Beadle, Luria, Delbruck, Sturtevant, Bridges, and others), as well as most geneticists today, saw Goldschmidt as having been largely “obstructionist” is useful historical (and/or sociological) data. Clearly, as this paper has tried to show, Goldschmidt's ideas were not all obstructionist, and his viewpoint that genes must be considered functionally was one which was clearly valid, premature as it may have been from an experimental and technique point of view. Perhaps Goldschmidt's major fault was that he developed alternative theories which were not easily testable. Nonetheless, his challenge to a fundamental and established idea brought forth a reaction from many members of the genetic community which indicates how unwilling they were to reconsider the formalized theory on which their work was based. While many of Goldschmidt's criticisms — and particularly his way of making them — arose out of his own idiosyncrasies, they were also a product of his times. His view of the nature of theory-construction, and his rejection of old-style reductionism and mechanism, were part of a growing awareness within the world scientific community that explanations based on reducing complex phenomena to ultimate particles or units were clearly inadequate. The success of the Mendelian-chromosome theory had obscured that fact for many geneticists, but to Goldschmidt it was a point that could not be allowed to pass unnoticed. (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)