Analysis of the DNA sequence and duplication history of human chromosome 15

Here we present a finished sequence of human chromosome 15, together with a high-quality gene catalogue. As chromosome 15 is one of seven human chromosomes with a high rate of segmental duplication, we have carried out a detailed analysis of the duplication structure of the chromosome. Segmental duplications in chromosome 15 are largely clustered in two regions, on proximal and distal 15q; the proximal region is notable because recombination among the segmental duplications can result in deletions causing Prader-Willi and Angelman syndromes. Sequence analysis shows that the proximal and distal regions of 15q share extensive ancient similarity. Using a simple approach, we have been able to reconstruct many of the events by which the current duplication structure arose. We find that most of the intrachromosomal duplications seem to share a common ancestry. Finally, we demonstrate that some remaining gaps in the genome sequence are probably due to structural polymorphisms between haplotypes; this may explain a significant fraction of the gaps remaining in the human genome.     

Optical turbulence profiling with single star SCIDAR technique

In order to characterize optical turbulence, we have developed a single star SCIDAR （SSS） for measurement of the distribution of Cn^2 with height. The SSS consists of a 40 cm telescope and a CCD camera for fast sampling of stellar scintillation pattern. Spatio- temporal auto and cross-correlation functions of the single star images are computed, providing vertical profiles of optical turbulence intensity C2（h） and wind speed V（h）. Using this new SSS experiment, profiles of turbulence can be obtained from the ground to the top of atmosphere, allowing the determination of seeing, isoplanatic angle and coherence time. Detailed characteristics of atmospheric optical turbulence are important for active and passive imaging, astronomical site testing, adaptive optics, laser communications, target tracking and designation, and laser beam control. We plan to improve the robotization of the SSS to be able to use it routinely even under harsh weather and altitude conditions that we expect to encounter on the high Tibetan plateau or at Dome A in Antarctica. SSS will also be applied for the site testing campaign of the future Chinese extremely large telescope.     

Common variants near TARDBP and EGR2 are associated with susceptibility to Ewing sarcoma

Ewing sarcoma, a pediatric tumor characterized by EWSR1-ETS fusions, is predominantly observed in populations of European ancestry. We performed a genome-wide association study (GWAS) of 401 French individuals with Ewing sarcoma, 684 unaffected French individuals and 3,668 unaffected individuals of European descent and living in the United States. We identified candidate risk loci at 1p36.22, 10q21 and 15q15. We replicated these loci in two independent sets of cases and controls. Joint analysis identified associations with rs9430161 (P = 1.4 × 10(-20); odds ratio (OR) = 2.2) located 25 kb upstream of TARDBP, rs224278 (P = 4.0 × 10(-17); OR = 1.7) located 5 kb upstream of EGR2 and, to a lesser extent, rs4924410 at 15q15 (P = 6.6 × 10(-9); OR = 1.5). The major risk haplotypes were less prevalent in Africans, suggesting that these loci could contribute to geographical differences in Ewing sarcoma incidence. TARDBP shares structural similarities with EWSR1 and FUS, which encode RNA binding proteins, and EGR2 is a target gene of EWSR1-ETS. Variants at these loci were associated with expression levels of TARDBP, ADO (encoding cysteamine dioxygenase) and EGR2.     

Cellular mechanisms responsible for cell-to-cell spreading of prions

Prions are infectious agents that cause fatal neurodegenerative diseases. Current evidence indicates that they are essentially composed of an abnormally folded protein (PrP^Sc). These abnormal aggregated PrP^Sc species multiply in infected cells by recruiting and converting the host PrP^C protein into new PrP^Sc. How prions move from cell to cell and progressively spread across the infected tissue is of crucial importance and may provide experimental opportunity to delay the progression of the disease. In infected cells, different mechanisms have been identified, including release of infectious extracellular vesicles and intercellular transfer of PrP^Sc-containing organelles through tunneling nanotubes. These findings should allow manipulation of the intracellular trafficking events targeting PrP^Sc in these particular subcellular compartments to experimentally address the relative contribution of these mechanisms to in vivo prion pathogenesis. In addition, such information may prompt further experimental strategies to decipher the causal roles of protein misfolding and aggregation in other human neurodegenerative diseases.     

Global trends of whole-genome duplications revealed by the ciliate Paramecium tetraurelia

The duplication of entire genomes has long been recognized as having great potential for evolutionary novelties, but the mechanisms underlying their resolution through gene loss are poorly understood. Here we show that in the unicellular eukaryote Paramecium tetraurelia, a ciliate, most of the nearly 40,000 genes arose through at least three successive whole-genome duplications. Phylogenetic analysis indicates that the most recent duplication coincides with an explosion of speciation events that gave rise to the P. aurelia complex of 15 sibling species. We observed that gene loss occurs over a long timescale, not as an initial massive event. Genes from the same metabolic pathway or protein complex have common patterns of gene loss, and highly expressed genes are over-retained after all duplications. The conclusion of this analysis is that many genes are maintained after whole-genome duplication not because of functional innovation but because of gene dosage constraints.     

Berezinskii-Kosterlitz-Thouless crossover in a trapped atomic gas

Any state of matter is classified according to its order, and the type of order that a physical system can possess is profoundly affected by its dimensionality. Conventional long-range order, as in a ferromagnet or a crystal, is common in three-dimensional systems at low temperature. However, in two-dimensional systems with a continuous symmetry, true long-range order is destroyed by thermal fluctuations at any finite temperature. Consequently, for the case of identical bosons, a uniform two-dimensional fluid cannot undergo Bose-Einstein condensation, in contrast to the three-dimensional case. However, the two-dimensional system can form a 'quasi-condensate' and become superfluid below a finite critical temperature. The Berezinskii-Kosterlitz-Thouless (BKT) theory associates this phase transition with the emergence of a topological order, resulting from the pairing of vortices with opposite circulation. Above the critical temperature, proliferation of unbound vortices is expected. Here we report the observation of a BKT-type crossover in a trapped quantum degenerate gas of rubidium atoms. Using a matter wave heterodyning technique, we observe both the long-wavelength fluctuations of the quasi-condensate phase and the free vortices. At low temperatures, the gas is quasi-coherent on the length scale set by the system size. As the temperature is increased, the loss of long-range coherence coincides with the onset of proliferation of free vortices. Our results provide direct experimental evidence for the microscopic mechanism underlying the BKT theory, and raise new questions regarding coherence and superfluidity in mesoscopic systems.     

DNA sequence and analysis of human chromosome 8

The International Human Genome Sequencing Consortium (IHGSC) recently completed a sequence of the human genome. As part of this project, we have focused on chromosome 8. Although some chromosomes exhibit extreme characteristics in terms of length, gene content, repeat content and fraction segmentally duplicated, chromosome 8 is distinctly typical in character, being very close to the genome median in each of these aspects. This work describes a finished sequence and gene catalogue for the chromosome, which represents just over 5% of the euchromatic human genome. A unique feature of the chromosome is a vast region of approximately 15 megabases on distal 8p that appears to have a strikingly high mutation rate, which has accelerated in the hominids relative to other sequenced mammals. This fast-evolving region contains a number of genes related to innate immunity and the nervous system, including loci that appear to be under positive selection--these include the major defensin (DEF) gene cluster and MCPH1, a gene that may have contributed to the evolution of expanded brain size in the great apes. The data from chromosome 8 should allow a better understanding of both normal and disease biology and genome evolution.     

Stratified prokaryote network in the oxic-anoxic transition of a deep-sea halocline

The chemical composition of the Bannock basin has been studied in some detail. We recently showed that unusual microbial populations, including a new division of Archaea (MSBL1), inhabit the NaCl-rich hypersaline brine. High salinities tend to reduce biodiversity, but when brines come into contact with fresher water the natural haloclines formed frequently contain gradients of other chemicals, including permutations of electron donors and acceptors, that may enhance microbial diversity, activity and biogeochemical cycling. Here we report a 2.5-m-thick chemocline with a steep NaCl gradient at 3.3 km within the water column betweeen Bannock anoxic hypersaline brine and overlying sea water. The chemocline supports some of the most biomass-rich and active microbial communities in the deep sea, dominated by Bacteria rather than Archaea, and including four major new divisions of Bacteria. Significantly higher metabolic activities were measured in the chemocline than in the overlying sea water and underlying brine; functional analyses indicate that a range of biological processes is likely to occur in the chemocline. Many prokaryotic taxa, including the phylogenetically new groups, were confined to defined salinities, and collectively formed a diverse, sharply stratified, deep-sea ecosystem with sufficient biomass to potentially contribute to organic geological deposits.