The genome sequence of the filamentous fungus Neurospora crassa

Neurospora crassa is a central organism in the history of twentieth-century genetics, biochemistry and molecular biology. Here, we report a high-quality draft sequence of the N. crassa genome. The approximately 40-megabase genome encodes about 10,000 protein-coding genes--more than twice as many as in the fission yeast Schizosaccharomyces pombe and only about 25% fewer than in the fruitfly Drosophila melanogaster. Analysis of the gene set yields insights into unexpected aspects of Neurospora biology including the identification of genes potentially associated with red light photobiology, genes implicated in secondary metabolism, and important differences in Ca2+ signalling as compared with plants and animals. Neurospora possesses the widest array of genome defence mechanisms known for any eukaryotic organism, including a process unique to fungi called repeat-induced point mutation (RIP). Genome analysis suggests that RIP has had a profound impact on genome evolution, greatly slowing the creation of new genes through genomic duplication and resulting in a genome with an unusually low proportion of closely related genes.     

A negative element in SMN2 exon 7 inhibits splicing in spinal muscular atrophy

Spinal muscular atrophy (SMA) is a relatively common neurodegenerative disease caused by homozygous loss of the survival motor neuron 1 (SMN1) gene. Humans possess a linked, nearly identical gene, SMN2, which produces a functional SMN protein but at levels insufficient to compensate for loss of SMN1 (refs. 1,2). A C/T transition at position +6 in exon 7 is all that differentiates the two genes, but this is sufficient to prevent efficient exon 7 splicing in SMN2 (refs. 2,3). Here we show that the C/T transition functions not to disrupt an exonic splicing enhancer (ESE) in SMN1 (ref. 4), as previously suggested, but rather to create an exonic splicing silencer (ESS) in SMN2. We show that this ESS functions as a binding site for a known repressor protein, hnRNP A1, which binds to SMN2 but not SMN1 exon 7 RNA. We establish the physiological importance of these results by using small interfering RNAs to reduce hnRNP A protein levels in living cells and show that this results in efficient SMN2 exon 7 splicing. Our findings not only define a new mechanism underlying the inefficient splicing of SMN2 exon 7 but also illustrate more generally the remarkable sensitivity and precision that characterizes control of mRNA splicing.     

A gravitationally lensed quasar with quadruple images separated by 14.62 arcseconds

Gravitational lensing is a powerful tool for the study of the distribution of dark matter in the Universe. The cold-dark-matter model of the formation of large-scale structures (that is, clusters of galaxies and even larger assemblies) predicts the existence of quasars gravitationally lensed by concentrations of dark matter so massive that the quasar images would be split by over 7 arcsec. Numerous searches for large-separation lensed quasars have, however, been unsuccessful. All of the roughly 70 lensed quasars known, including the first lensed quasar discovered, have smaller separations that can be explained in terms of galaxy-scale concentrations of baryonic matter. Although gravitationally lensed galaxies with large separations are known, quasars are more useful cosmological probes because of the simplicity of the resulting lens systems. Here we report the discovery of a lensed quasar, SDSS J1004 + 4112, which has a maximum separation between the components of 14.62 arcsec. Such a large separation means that the lensing object must be dominated by dark matter. Our results are fully consistent with theoretical expectations based on the cold-dark-matter model.     

Recent ice ages on Mars

A key pacemaker of ice ages on the Earth is climatic forcing due to variations in planetary orbital parameters. Recent Mars exploration has revealed dusty, water-ice-rich mantling deposits that are layered, metres thick and latitude dependent, occurring in both hemispheres from mid-latitudes to the poles. Here we show evidence that these deposits formed during a geologically recent ice age that occurred from about 2.1 to 0.4 Myr ago. The deposits were emplaced symmetrically down to latitudes of approximately 30 degrees--equivalent to Saudi Arabia and the southern United States on the Earth--in response to the changing stability of water ice and dust during variations in obliquity (the angle between Mars' pole of rotation and the ecliptic plane) reaching 30-35 degrees. Mars is at present in an 'interglacial' period, and the ice-rich deposits are undergoing reworking, degradation and retreat in response to the current instability of near-surface ice. Unlike the Earth, martian ice ages are characterized by warmer polar climates and enhanced equatorward transport of atmospheric water and dust to produce widespread smooth deposits down to mid-latitudes.     

Field sports and conservation in the United Kingdom

Many natural habitats exist on privately owned land outside protected areas, but few governments can afford to enforce or subsidize conservation of this biodiversity. Even in some developed countries, conservation subsidy schemes have only achieved limited success. Fortunately, some landowners may be willing to accept management costs in return for other benefits, although this remains controversial when it involves the killing of charismatic species. For example, participants in British field sports, such as fox hunting and game-bird shooting, may voluntarily conserve important habitats that are required by quarry species. Here we report results from a multidisciplinary study that addressed this issue by focusing on three sites across central England. We found that landowners participating in field sports maintained the most established woodland and planted more new woodland and hedgerows than those who did not, despite the equal availability of subsidies. Therefore, voluntary habitat management appears to be important for biodiversity conservation in Britain. Current debates on the future of field sports in Britain, and similar activities globally, may benefit from considering their utility as incentives to conserve additional habitat on private land.     

Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing

Nicastrin, a transmembrane glycoprotein, forms high molecular weight complexes with presenilin 1 and presenilin 2. Suppression of nicastrin expression in Caenorhabditis elegans embryos induces a subset of notch/glp-1 phenotypes similar to those induced by simultaneous null mutations in both presenilin homologues of C. elegans (sel-12 and hop-1). Nicastrin also binds carboxy-terminal derivatives of beta-amyloid precursor protein (betaAPP), and modulates the production of the amyloid beta-peptide (A beta) from these derivatives. Missense mutations in a conserved hydrophilic domain of nicastrin increase A beta42 and A beta40 peptide secretion. Deletions in this domain inhibit A beta production. Nicastrin and presenilins are therefore likely to be functional components of a multimeric complex necessary for the intramembranous proteolysis of proteins such as Notch/GLP-1 and betaAPP.