Sequence and analysis of chromosome 2 of the plant Arabidopsis thaliana

Arabidopsis thaliana (Arabidopsis) is unique among plant model organisms in having a small genome (130-140 Mb), excellent physical and genetic maps, and little repetitive DNA. Here we report the sequence of chromosome 2 from the Columbia ecotype in two gap-free assemblies (contigs) of 3.6 and 16 megabases (Mb). The latter represents the longest published stretch of uninterrupted DNA sequence assembled from any organism to date. Chromosome 2 represents 15% of the genome and encodes 4,037 genes, 49% of which have no predicted function. Roughly 250 tandem gene duplications were found in addition to large-scale duplications of about 0.5 and 4.5 Mb between chromosomes 2 and 1 and between chromosomes 2 and 4, respectively. Sequencing of nearly 2 Mb within the genetically defined centromere revealed a low density of recognizable genes, and a high density and diverse range of vestigial and presumably inactive mobile elements. More unexpected is what appears to be a recent insertion of a continuous stretch of 75% of the mitochondrial genome into chromosome 2.     

A structural change in the kinesin motor protein that drives motility

Kinesin motors power many motile processes by converting ATP energy into unidirectional motion along microtubules. The force-generating and enzymatic properties of conventional kinesin have been extensively studied; however, the structural basis of movement is unknown. Here we have detected and visualized a large conformational change of an approximately 15-amino-acid region (the neck linker) in kinesin using electron paramagnetic resonance, fluorescence resonance energy transfer, pre-steady state kinetics and cryo-electron microscopy. This region becomes immobilized and extended towards the microtubule 'plus' end when kinesin binds microtubules and ATP, and reverts to a more mobile conformation when gamma-phosphate is released after nucleotide hydrolysis. This conformational change explains both the direction of kinesin motion and processive movement by the kinesin dimer.     

Msh2 deficiency prevents in vivo somatic instability of the CAG repeat in Huntington disease transgenic mice

Huntington disease (HD), an autosomal dominant, progressive neurodegenerative disorder, is caused by an expanded CAG repeat sequence leading to an increase in the number of glutamine residues in the encoded protein. The normal CAG repeat range is 5-36, whereas 38 or more repeats are found in the diseased state; the severity of disease is roughly proportional to the number of CAG repeats. HD shows anticipation, in which subsequent generations display earlier disease onsets due to intergenerational repeat expansion. For longer repeat lengths, somatic instability of the repeat size has been observed both in human cases at autopsy and in transgenic mouse models containing either a genomic fragment of human HD exon 1 (ref. 9) or an expanded repeat inserted into the endogenous mouse gene Hdh (ref. 10). With increasing repeat number, the protein changes conformation and becomes increasingly prone to aggregation, suggesting important functional correlations between repeat length and pathology. Because dinucleotide repeat instability is known to increase when the mismatch repair enzyme MSH2 is missing, we examined instability of the HD CAG repeat by crossing transgenic mice carrying exon 1 of human HD (ref. 16) with Msh2-/- mice. Our results show that Msh2 is required for somatic instability of the CAG repeat.     

Childbearing outside marriage in western Europe

Across most European states in recent decades there have been significant increases in childbearing outside marriage. This article examines the extent to which women have their first child in one of four settings: prior to any partnership; in their first cohabiting partnership; in first marriage; and after a first partnership. Temporal changes in these behaviours and variation according to background characteristics of the women are also examined. For the women who had a child outside any partnership, we examine the extent to which they go on to form partnerships and how long after the birth this happens. For those who had their first child within a cohabiting union, we examine the extent to which they marry and how long after the birth this occurs. Finally, we investigate whether children born within cohabiting unions that do and do not convert into marriages are more or less likely than those born within marriage to see their parents separate.     

Bacterial suicide through stress

Outside of the laboratory, bacterial cells are constantly exposed to stressful conditions, and an ability to resist those stresses is essential to their survival. However, the degree of stress required to bring about cell death varies with growth phase, amongst other parameters. Exponential phase cells are significantly more sensitive to stress than stationary phase ones, and a novel hypothesis has recently been advanced to explain this difference in sensitivity, the suicide response. Essentially, the suicide response predicts that rapidly growing and respiring bacterial cells will suffer growth arrest when subjected to relatively mild stresses, but their metabolism will continue: a burst of free-radical production results from this uncoupling of growth from metabolism, and it is this free-radical burst that is lethal to the cells, rather than the stress per se. The suicide response hypothesis unifies a variety of previously unrelated empirical observations, for instance induction of superoxide dismutase by heat shock, alkyl-hydroperoxide reductase by osmotic shock and catalase by ethanol shock. The suicide response also has major implications for current [food] processing methods. Received 29 March 1999; received after revision 14 May 1999; accepted 17 May 1999     

Regulation of cytokinesis

At the end of mitosis, daughter cells are separated from each other by cytokinesis. This process involves equal partitioning and segregation of cytoplasm between the two cells. Despite years of study, the mechanism driving cytokinesis in animal cells is not fully understood. Actin and myosin are major components of the contractile ring, the structure at the equator between the dividing cells that provides the force necessary to constrict the cytoplasm. Despite this, there are also tantalizing results suggesting that cytokinesis can occur in the absence of myosin. It is unclear what the roles are of the few other contractile ring components identified to date. While it has been difficult to identify important proteins involved in cytokinesis, it has been even more challenging to pinpoint the regulatory mechanisms that govern this vital process. Cytokinesis must be precisely controlled both spatially and temporally; potential regulators of these parameters are just beginning to be identified. This review discusses the recent progress in our understanding of cytokinesis in animal cells and the mechanisms that may regulate it. Received 24 August 1998; received after revision 9 October 1998; accepted 9 October 1998