A model for SOS-lesion-targeted mutations in Escherichia coli

The UmuD'2C protein complex (Escherichia coli pol V) is a low-fidelity DNA polymerase (pol) that copies damaged DNA in the presence of RecA, single-stranded-DNA binding protein (SSB) and the beta,gamma-processivity complex of E. coli pol III (ref. 4). Here we propose a model to explain SOS-lesion-targeted mutagenesis, assigning specific biochemical functions for each protein during translesion synthesis. (SOS lesion-targeted mutagenesis occurs when pol V is induced as part of the SOS response to DNA damage and incorrectly incorporates nucleotides opposite template lesions.) Pol V plus SSB catalyses RecA filament disassembly in the 3' to 5' direction on the template, ahead of the polymerase, in a reaction that does not involve ATP hydrolysis. Concurrent ATP-hydrolysis-driven filament disassembly in the 5' to 3' direction results in a bidirectional stripping of RecA from the template strand. The bidirectional collapse of the RecA filament restricts DNA synthesis by pol V to template sites that are proximal to the lesion, thereby minimizing the occurrence of untargeted mutations at undamaged template sites.     

Geochemical evidence for magmatic water within Mars from pyroxenes in the Shergotty meteorite

Observations of martian surface morphology have been used to argue that an ancient ocean once existed on Mars. It has been thought that significant quantities of such water could have been supplied to the martian surface through volcanic outgassing, but this suggestion is contradicted by the low magmatic water content that is generally inferred from chemical analyses of igneous martian meteorites. Here, however, we report the distributions of trace elements within pyroxenes of the Shergotty meteorite--a basalt body ejected 175 million years ago from Mars--as well as hydrous and anhydrous crystallization experiments that, together, imply that water contents of pre-eruptive magma on Mars could have been up to 1.8%. We found that in the Shergotty meteorite, the inner cores of pyroxene minerals (which formed at depth in the martian crust) are enriched in soluble trace elements when compared to the outer rims (which crystallized on or near to the martian surface). This implies that water was present in pyroxenes at depth but was largely lost as pyroxenes were carried to the surface during magma ascent. We conclude that ascending magmas possibly delivered significant quantities of water to the martian surface in recent times, reconciling geologic and petrologic constraints on the outgassing history of Mars.     

A massive protocluster of galaxies at a redshift of z ≈ 5.3

Massive clusters of galaxies have been found that date from as early as 3.9 billion years (3.9 Gyr; z = 1.62) after the Big Bang, containing stars that formed at even earlier epochs. Cosmological simulations using the current cold dark matter model predict that these systems should descend from 'protoclusters'-early overdensities of massive galaxies that merge hierarchically to form a cluster. These protocluster regions themselves are built up hierarchically and so are expected to contain extremely massive galaxies that can be observed as luminous quasars and starbursts. Observational evidence for this picture, however, is sparse because high-redshift protoclusters are rare and difficult to observe. Here we report a protocluster region that dates from 1 Gyr (z = 5.3) after the Big Bang. This cluster of massive galaxies extends over more than 13 megaparsecs and contains a luminous quasar as well as a system rich in molecular gas. These massive galaxies place a lower limit of more than 4 × 10(11) solar masses of dark and luminous matter in this region, consistent with that expected from cosmological simulations for the earliest galaxy clusters.     

Domination of heliosheath pressure by shock-accelerated pickup ions from observations of neutral atoms

The solar wind blows an immense magnetic bubble, the heliosphere, in the local interstellar medium (mostly neutral gas) flowing by the Sun. Recent measurements by Voyager 2 across the termination shock, where the solar wind is slowed to subsonic speeds before entering the heliosheath, found that the shocked solar wind plasma contains only approximately 20 per cent of the energy released by the termination shock, whereas energetic particles above approximately 28 keV contain only approximately 10 per cent; approximately 70 per cent of the energy is unaccounted for, leading to speculation that the unmeasured pickup ions or energetic particles below 28 keV contain the missing energy. Here we report the detection and mapping of heliosheath energetic ( approximately 4-20 keV) neutral atoms produced by charge exchange of suprathermal ions with interstellar neutral atoms. The energetic neutral atoms come from a source approximately 60 degrees wide in longitude straddling the direction of the local interstellar medium. Their energy spectra resemble those of solar wind pickup ions, but with a knee at approximately 11 keV instead of approximately 4 keV, indicating that their parent ions are pickup ions energized by the termination shock. These termination-shock-energized pickup ions contain the missing approximately 70 per cent of the energy dissipated in the termination shock, and they dominate the pressure in the heliosheath.     

The genome of the choanoflagellate Monosiga brevicollis and the origin of metazoans

Choanoflagellates are the closest known relatives of metazoans. To discover potential molecular mechanisms underlying the evolution of metazoan multicellularity, we sequenced and analysed the genome of the unicellular choanoflagellate Monosiga brevicollis. The genome contains approximately 9,200 intron-rich genes, including a number that encode cell adhesion and signalling protein domains that are otherwise restricted to metazoans. Here we show that the physical linkages among protein domains often differ between M. brevicollis and metazoans, suggesting that abundant domain shuffling followed the separation of the choanoflagellate and metazoan lineages. The completion of the M. brevicollis genome allows us to reconstruct with increasing resolution the genomic changes that accompanied the origin of metazoans.     

A variant associated with nicotine dependence, lung cancer and peripheral arterial disease

Smoking is a leading cause of preventable death, causing about 5 million premature deaths worldwide each year. Evidence for genetic influence on smoking behaviour and nicotine dependence (ND) has prompted a search for susceptibility genes. Furthermore, assessing the impact of sequence variants on smoking-related diseases is important to public health. Smoking is the major risk factor for lung cancer (LC) and is one of the main risk factors for peripheral arterial disease (PAD). Here we identify a common variant in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 with an effect on smoking quantity, ND and the risk of two smoking-related diseases in populations of European descent. The variant has an effect on the number of cigarettes smoked per day in our sample of smokers. The same variant was associated with ND in a previous genome-wide association study that used low-quantity smokers as controls, and with a similar approach we observe a highly significant association with ND. A comparison of cases of LC and PAD with population controls each showed that the variant confers risk of LC and PAD. The findings provide a case study of a gene-environment interaction, highlighting the role of nicotine addiction in the pathology of other serious diseases.