The DNA sequence and analysis of human chromosome 13

Chromosome 13 is the largest acrocentric human chromosome. It carries genes involved in cancer including the breast cancer type 2 (BRCA2) and retinoblastoma (RB1) genes, is frequently rearranged in B-cell chronic lymphocytic leukaemia, and contains the DAOA locus associated with bipolar disorder and schizophrenia. We describe completion and analysis of 95.5 megabases (Mb) of sequence from chromosome 13, which contains 633 genes and 296 pseudogenes. We estimate that more than 95.4% of the protein-coding genes of this chromosome have been identified, on the basis of comparison with other vertebrate genome sequences. Additionally, 105 putative non-coding RNA genes were found. Chromosome 13 has one of the lowest gene densities (6.5 genes per Mb) among human chromosomes, and contains a central region of 38 Mb where the gene density drops to only 3.1 genes per Mb.     

Development of behavioural tolerance to nicotine in the rat

Résumé On a donné de la nicotine à des rats une fois par jour, pendant 10 jours. L'activité des animaux a d'abord diminué, mais après quelques administrations de la drogue, on constata une accoutumance à ces effets. L'administration terminée, l'activité a augmenté.

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This work was supported by a grant from the Tobacco Research Council.     

A radiation hybrid map of the zebrafish genome.

Recent large-scale mutagenesis screens have made the zebrafish the first vertebrate organism to allow a forward genetic approach to the discovery of developmental control genes. Mutations can be cloned positionally, or placed on a simple sequence length polymorphism (SSLP) map to match them with mapped candidate genes and expressed sequence tags (ESTs). To facilitate the mapping of candidate genes and to increase the density of markers available for positional cloning, we have created a radiation hybrid (RH) map of the zebrafish genome. This technique is based on somatic cell hybrid lines produced by fusion of lethally irradiated cells of the species of interest with a rodent cell line. Random fragments of the donor chromosomes are integrated into recipient chromosomes or retained as separate minichromosomes. The radiation-induced breakpoints can be used for mapping in a manner analogous to genetic mapping, but at higher resolution and without a need for polymorphism. Genome-wide maps exist for the human, based on three RH panels of different resolutions, as well as for the dog, rat and mouse. For our map of the zebrafish genome, we used an existing RH panel and 1,451 sequence tagged site (STS) markers, including SSLPs, cloned candidate genes and ESTs. Of these, 1,275 (87.9%) have significant linkage to at least one other marker. The fraction of ESTs with significant linkage, which can be used as an estimate of map coverage, is 81.9%. We found the average marker retention frequency to be 18.4%. One cR3000 is equivalent to 61 kb, resulting in a potential resolution of approximately 350 kb.     

Microbiology: eukaryotic diversity in Spain's River of Fire

The Rio Tinto, known by the Phoenicians as 'Ur-yero', or 'River of Fire', because of its deep red colour and high acidity, flows through the world's largest pyritic belt in southwestern Spain. Surprisingly, eukaryotic microbes are the principal contributors of biomass in this hostile river, which has a pH of 2 and contains much higher concentrations of heavy metals than are typically found in fresh waters. Here we show that the Rio Tinto shows an unexpected degree of eukaryotic diversity and includes new lineages that we have identified by sequence analysis of genes encoding small-subunit ribosomal RNAs. The diversity of these eukaryotes is much greater than that of prokaryotes, whose metabolism is responsible for the extreme environment.     

The mechanism of membrane-associated steps in tail-anchored protein insertion

Tail-anchored (TA) membrane proteins destined for the endoplasmic reticulum are chaperoned by cytosolic targeting factors that deliver them to a membrane receptor for insertion. Although a basic framework for TA protein recognition is now emerging, the decisive targeting and membrane insertion steps are not understood. Here we reconstitute the TA protein insertion cycle with purified components, present crystal structures of key complexes between these components and perform mutational analyses based on the structures. We show that a committed targeting complex, formed by a TA protein bound to the chaperone ATPase Get3, is initially recruited to the membrane through an interaction with Get2. Once the targeting complex has been recruited, Get1 interacts with Get3 to drive TA protein release in an ATPase-dependent reaction. After releasing its TA protein cargo, the now-vacant Get3 recycles back to the cytosol concomitant with ATP binding. This work provides a detailed structural and mechanistic framework for the minimal TA protein insertion cycle.     

A giant outburst two years before the core-collapse of a massive star

The death of massive stars produces a variety of supernovae, which are linked to the structure of the exploding stars. The detection of several precursor stars of type II supernovae has been reported (see, for example, ref. 3), but we do not yet have direct information on the progenitors of the hydrogen-deficient type Ib and Ic supernovae. Here we report that the peculiar type Ib supernova SN 2006jc is spatially coincident with a bright optical transient that occurred in 2004. Spectroscopic and photometric monitoring of the supernova leads us to suggest that the progenitor was a carbon-oxygen Wolf-Rayet star embedded within a helium-rich circumstellar medium. There are different possible explanations for this pre-explosion transient. It appears similar to the giant outbursts of luminous blue variable stars (LBVs) of 60-100 solar masses, but the progenitor of SN 2006jc was helium- and hydrogen-deficient (unlike LBVs). An LBV-like outburst of a Wolf-Rayet star could be invoked, but this would be the first observational evidence of such a phenomenon. Alternatively, a massive binary system composed of an LBV that erupted in 2004, and a Wolf-Rayet star exploding as SN 2006jc, could explain the observations.