Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours.

Mutations in the p53 tumour-suppressor gene are the most frequently observed genetic lesions in human cancers. To investigate the role of the p53 gene in mammalian development and tumorigenesis, a null mutation was introduced into the gene by homologous recombination in murine embryonic stem cells. Mice homozygous for the null allele appear normal but are prone to the spontaneous development of a variety of neoplasms by 6 months of age. These observations indicate that a normal p53 gene is dispensable for embryonic development, that its absence predisposes the animal to neoplastic disease, and that an oncogenic mutant form of p53 is not obligatory for the genesis of many types of tumours.     

Tibetan plateau river incision inhibited by glacial stabilization of the Tsangpo gorge

A considerable amount of research has focused on how and when the Tibetan plateau formed in the wake of tectonic convergence between India and Asia. Although far less enquiry has addressed the controls on river incision into the plateau itself, widely accepted theory predicts that steep fluvial knick points (river reaches with very steep gradients) in the eastern Himalayan syntaxis at the southeastern plateau margin should erode rapidly, driving a wave of incision back into the plateau. Preservation of the plateau edge thus presents something of a conundrum that may be resolved by invoking either differential rock uplift matching erosional decay, or other mechanisms for retarding bedrock river incision in this region where high stream power excludes the potential for aridity as a simple limit to dissection of the plateau. Here we report morphologic evidence showing that Quaternary depression of the regional equilibrium line altitude, where long-term glacier mass gain equals mass loss, was sufficient to repeatedly form moraine dams on major rivers: such damming substantially impeded river incision into the southeastern edge of the Tibetan plateau through the coupled effects of upstream impoundment and interglacial aggradation. Such glacial stabilization of the resulting highly focused river incision centred on the Tsangpo gorge could further contribute to initiating and accentuating a locus of rapid exhumation, known as tectonic anaeurysm.     

Evidence for enhanced mixing over rough topography in the abyssal ocean

The overturning circulation of the ocean plays an important role in modulating the Earth's climate. But whereas the mechanisms for the vertical transport of water into the deep ocean--deep water formation at high latitudes--and horizontal transport in ocean currents have been largely identified, it is not clear how the compensating vertical transport of water from the depths to the surface is accomplished. Turbulent mixing across surfaces of constant density is the only viable mechanism for reducing the density of the water and enabling it to rise. However, measurements of the internal wave field, the main source of energy for mixing, and of turbulent dissipation rates, have typically implied diffusivities across surfaces of equal density of only approximately 0.1 cm2 s(-1), too small to account for the return flow. Here we report measurements of tracer dispersion and turbulent energy dissipation in the Brazil basin that reveal diffusivities of 2-4 cm2 s(-1) at a depth of 500 m above abyssal hills on the flank of the Mid-Atlantic Ridge, and approximately 10 cm2 s(-1) nearer the bottom. This amount of mixing, probably driven by breaking internal waves that are generated by tidal currents flowing over the rough bathymetry, may be large enough to close the buoyancy budget for the Brazil basin and suggests a mechanism for closing the global overturning circulation.     

Global variation in copy number in the human genome

Copy number variation (CNV) of DNA sequences is functionally significant but has yet to be fully ascertained. We have constructed a first-generation CNV map of the human genome through the study of 270 individuals from four populations with ancestry in Europe, Africa or Asia (the HapMap collection). DNA from these individuals was screened for CNV using two complementary technologies: single-nucleotide polymorphism (SNP) genotyping arrays, and clone-based comparative genomic hybridization. A total of 1,447 copy number variable regions (CNVRs), which can encompass overlapping or adjacent gains or losses, covering 360 megabases (12% of the genome) were identified in these populations. These CNVRs contained hundreds of genes, disease loci, functional elements and segmental duplications. Notably, the CNVRs encompassed more nucleotide content per genome than SNPs, underscoring the importance of CNV in genetic diversity and evolution. The data obtained delineate linkage disequilibrium patterns for many CNVs, and reveal marked variation in copy number among populations. We also demonstrate the utility of this resource for genetic disease studies.     

Apparent absence of transposable elements related to the P elements of D. melanogaster in other species of Drosophila

P elements are transposable elements found in P strain, but usually not in M strain, Drosophila melanogaster, and are responsible for the hybrid dysgenesis that occurs when male D. melanogaster of the P strain mate with females of the M strain (ref. 1 and references therein). Several P elements, which vary in length and genetic effects, have now been cloned. To investigate the evolutionary origin of P elements, we have used a cloned copy of a D. melanogaster P element to look for related sequences in the genomes of six other Drosophila species. We report here that, unlike many other transposable elements found in D. melanogaster, which seem also to be present in other Drosophila species, we have found no sequences closely enough related to P elements to be detected by DNA hybridization in any other Drosophila species. This result supports the hypothesis that P elements have recently invaded D. melanogaster by horizontal transmission.     

Genomic and functional adaptation in surface ocean planktonic prokaryotes

The understanding of marine microbial ecology and metabolism has been hampered by the paucity of sequenced reference genomes. To this end, we report the sequencing of 137 diverse marine isolates collected from around the world. We analysed these sequences, along with previously published marine prokaryotic genomes, in the context of marine metagenomic data, to gain insights into the ecology of the surface ocean prokaryotic picoplankton (0.1-3.0?μm size range). The results suggest that the sequenced genomes define two microbial groups: one composed of only a few taxa that are nearly always abundant in picoplanktonic communities, and the other consisting of many microbial taxa that are rarely abundant. The genomic content of the second group suggests that these microbes are capable of slow growth and survival in energy-limited environments, and rapid growth in energy-rich environments. By contrast, the abundant and cosmopolitan picoplanktonic prokaryotes for which there is genomic representation have smaller genomes, are probably capable of only slow growth and seem to be relatively unable to sense or rapidly acclimate to energy-rich conditions. Their genomic features also lead us to propose that one method used to avoid predation by viruses and/or bacterivores is by means of slow growth and the maintenance of low biomass.     

Dystrophic mice show age related muscle fibre and myelinated axon losses

Although many differences between age matched normal and dystrophic animals have been found, there have been few demonstrations of a time related quantitative change from normal to a characteristically dystrophic situation within the dystrophic strain itself. Here we report such a change-normal numbers of muscle fibres present in young dystrophic mice were rapidly lost, such that older animals showed the reduced number of muscle fibres characteristic of murine dystrophy. Although these losses began after a demonstrable loss of myelinated axons had occurred, it is not possible to say if the loss of muscle fibres was a result of the loss of nerve fibres.     

Common sequence variants on 20q11.22 confer melanoma susceptibility

We conducted a genome-wide association pooling study for cutaneous melanoma and performed validation in samples totaling 2,019 cases and 2,105 controls. Using pooling, we identified a new melanoma risk locus on chromosome 20 (rs910873 and rs1885120), with replication in two further samples (combined P < 1 x 10(-15)). The per allele odds ratio was 1.75 (1.53, 2.01), with evidence for stronger association in early-onset cases.     

A sequence-based variation map of 8.27 million SNPs in inbred mouse strains

A dense map of genetic variation in the laboratory mouse genome will provide insights into the evolutionary history of the species and lead to an improved understanding of the relationship between inter-strain genotypic and phenotypic differences. Here we resequence the genomes of four wild-derived and eleven classical strains. We identify 8.27 million high-quality single nucleotide polymorphisms (SNPs) densely distributed across the genome, and determine the locations of the high (divergent subspecies ancestry) and low (common subspecies ancestry) SNP-rate intervals for every pairwise combination of classical strains. Using these data, we generate a genome-wide haplotype map containing 40,898 segments, each with an average of three distinct ancestral haplotypes. For the haplotypes in the classical strains that are unequivocally assigned ancestry, the genetic contributions of the Mus musculus subspecies--M. m. domesticus, M. m. musculus, M. m. castaneus and the hybrid M. m. molossinus--are 68%, 6%, 3% and 10%, respectively; the remaining 13% of haplotypes are of unknown ancestral origin. The considerable regional redundancy of the SNP data will facilitate imputation of the majority of these genotypes in less-densely typed classical inbred strains to provide a complete view of variation in additional strains.