Genesis of ancestral haplotypes: RNA modifications and reverse transcription–mediated polymorphisms

Understanding the genesis of the block haplotype structure of the genome is a major challenge. With the completion of the sequencing of the Human Genome and the initiation of the HapMap project the concept that the chromosomes of the mammalian genome are a mosaic, or patchwork, of conserved extended block haplotype sequences is now accepted by the mainstream genomics research community. Ancestral Haplotypes (AHs) can be viewed as a recombined string of smaller Polymorphic Frozen Blocks (PFBs). How have such variant extended DNA sequence tracts emerged in evolution? Here the relevant literature on the problem is reviewed from various fields of molecular and cell biology particularly molecular immunology and comparative and functional genomics. Based on our synthesis we then advance a testable molecular and cellular model. A critical part of the analysis concerns the origin of the strand biased mutation signatures in the transcribed regions of the human and higher primate genome, A-to-G versus T-to-C (ratio ~1.5 fold) and C-to-T versus G-to-A (≥1.5 fold). A comparison and evaluation of the current state of the fields of immunoglobulin Somatic Hypermutation (SHM) and Transcription-Coupled DNA Repair focused on how mutations in newly synthesized RNA might be copied back to DNA thus accounting for some of the genome-wide strand biases (e.g., the A-to-G vs T-to-C component of the strand biased spectrum). We hypothesize that the genesis of PFBs and extended AHs occurs during mutagenic episodes in evolution (e.g., retroviral infections) and that many of the critical DNA sequence diversifying events occur first at the RNA level, e.g., recombination between RNA strings resulting in tandem and dispersed RNA duplications (retroduplications), RNA mutations via adenosine-to-inosine pre-mRNA editing events as well as error prone RNA synthesis. These are then copied back into DNA by a cellular reverse transcription process (also likely to be error-prone) that we have called "reverse transcription-mediated long DNA conversion." Finally we suggest that all these activities and others can be envisaged as being brought physically under the umbrella of special sites in the nucleus involved in transcription known as "transcription factories."

The nature and formation of cristobalite at the Soufrière Hills volcano, Montserrat: implications for the petrology and stability of silicic lava domes

Cristobalite is commonly found in the dome lava of silicic volcanoes but is not a primary magmatic phase; its presence indicates that the composition and micro-structure of dome lavas evolve during, and after, emplacement. Nine temporally and mineralogically diverse dome samples from the Soufrière Hills volcano (SHV), Montserrat, are analysed to provide the first detailed assessment of the nature and mode of cristobalite formation in a volcanic dome. The dome rocks contain up to 11 wt.% cristobalite, as defined by X-ray diffraction. Prismatic and platy forms of cristobalite, identified by scanning electron microscopy (SEM), are commonly found in pores and fractures, suggesting that they have precipitated from a vapour phase. Feathery crystallites and micro-crystals of cristobalite and quartz associated with volcanic glass, identified using SEM-Raman, are interpreted to have formed by varying amounts of devitrification. We discuss mechanisms of silica transport and cristobalite formation, and their implications for petrological interpretations and dome stability. We conclude: (1) that silica may be transported in the vapour phase locally, or from one part of the magmatic system to another; (2) that the potential for transport of silica into the dome should not be neglected in petrological and geochemical studies because the addition of non-magmatic phases may affect whole rock composition; and (3) that the extent of cristobalite mineralisation in the dome at SHV is sufficient to reduce porosity—hence, permeability—and may impact on the mechanical strength of the dome rock, thereby potentially affecting dome stability

Field deployments of a self-contained subsea platform for acoustic monitoring of the environment around marine renewable energy structurea

The drive towards sustainable energy has seen rapid development of marine renewable energy devices, and current efforts are focusing on wave and tidal stream energy. The NERC/DEFRA collaboration FLOWBEC-4D (Flow, Water column & Benthic Ecology 4D) is addressing the lack of knowledge of the environmental and ecological effects of installing and operating large arrays of wave and tidal energy devices. The FLOWBEC sonar platform combines a number of instruments to record information at a range of physical and multi-trophic levels. Data are recorded at a resolution of several measurements per second, for durations of 2 weeks to capture an entire spring-neap tidal cycle. An upward-facing multifrequency Simrad EK60 echosounder (38, 120 and 200 kHz) is synchronized with an upward-facing Imagenex 837B Delta T multibeam sonar (120° × 20° beamwidth, 260 kHz) aligned with the tidal flow. An ADV is used for local current measurements and a fluorometer is used to measure chlorophyll (as a proxy for plankton) and turbidity. The platform is self-contained with no cables or anchors, facilitating rapid deployment and recovery in high-energy sites and flexibility in allowing baseline data to be gathered. Five 2-week deployments were completed in 2012 and 2013 at wave and tidal energy sites, both in the presence and absence of renewable energy structures. These surveys were conducted at the European Marine Energy Centre, Orkney, UK. Algorithms for noise removal, target detection and target tracking have been written using a combination of LabVIEW, MATLAB and Echoview. Target morphology, behavior and frequency response are used to aid target classification, with concurrent shore-based seabird observations used to ground truth the acoustic data. Using this information, the depth preference and interactions of birds, fish schools and marine mammals with renewable energy structures can be tracked. Seabird and mammal dive profiles, predator-prey interactions a- d the effect of hydrodynamic processes during foraging events throughout the water column can also be analyzed. These datasets offer insights into how fish, seabirds and marine mammals successfully forage within dynamic marine habitats and also whether individuals face collision risks with tidal stream turbines. Measurements from the subsea platform are complemented by 3D hydrodynamic model data and concurrent shore-based marine X-band radar. This range of concurrent fine-scale information across physical and trophic levels will improve our understanding of how the fine-scale physical influence of currents, waves and turbulence at tidal and wave energy sites affect the behavior of marine wildlife, and how tidal and wave energy devices might alter the behavior of such wildlife. Together, the results from these deployments increase our environmental understanding of the physical and ecological effects of installing and operating marine renewable energy devices. These results can be used to guide marine spatial planning, device design, licensing and operation, as individual devices are scaled up to arrays and new sites are considered. The combination of our current technology and analytical approach can help to de-risk the licensing process by providing a higher level of certainty about the behavior of a range of mobile marine species in high energy environments. It is likely that this approach will lead to greater mechanistic understanding of how and why mobile predators use these high energy areas for foraging. If a fuller understanding and quantification can be achieved at single demonstration scales, and these are found to be similar, then the predictive power of the outcomes might lead to a wider strategic approach to monitoring and possibly lead to a reduction in the level of monitoring required at each commercial site

Injection of Ballistic Hot Electrons and Cool Holes in a Two-Dimensional Electron Gas

We have constructed a novel magnetic spectrometer to study the dynamics of hot electrons and cool missing electron states injected by quantum point contacts in the two-dimensional electron gas of a GaAs-AlxGa1-xAs heterostructure. The mean free path of these quasi-particles is found to be longer than recent theoretical estimates. The injection energy of the particles is found to be anomalously low as the point contact approaches pinch-off, and also for high bias voltages.

Genomic evolution and polymorphism: Segmental duplications and haplotypes at 108 regions on 21 chromosomes

We describe here extensive, previously unknown, genomic polymorphism in 120 regions, covering 19 autosomes and both sex chromosomes. Each contains duplication within multigene clusters. Of these, 108 are extremely polymorphic with multiple haplotypes.We used the genomic matching technique (GMT), previously used to characterise the major histocompatibility complex (MHC) and regulators of complement activation (RCA).This genome-wide extension of this technique enables the examination of many underlying cis, trans and epistatic interactions responsible for phenotypic differences especially in relation to individuality, evolution and disease susceptibility.The extent of the diversity could not have been predicted and suggests a new model of primate evolution based on conservation of polymorphism rather than de novo mutation

Darkness visible: reflections on underground ecology

1 Soil science and ecology have developed independently, making it difficult for ecologists to contribute to urgent current debates on the destruction of the global soil resource and its key role in the global carbon cycle. Soils are believed to be exceptionally biodiverse parts of ecosystems, a view confirmed by recent data from the UK Soil Biodiversity Programme at Sourhope, Scotland, where high diversity was a characteristic of small organisms, but not of larger ones. Explaining this difference requires knowledge that we currently lack about the basic biology and biogeography of micro-organisms. 2 It seems inherently plausible that the high levels of biological diversity in soil play some part in determining the ability of soils to undertake ecosystem-level processes, such as carbon and mineral cycling. However, we lack conceptual models to address this issue, and debate about the role of biodiversity in ecosystem processes has centred around the concept of functional redundancy, and has consequently been largely semantic. More precise construction of our experimental questions is needed to advance understanding. 3 These issues are well illustrated by the fungi that form arbuscular mycorrhizas, the Glomeromycota. This ancient symbiosis of plants and fungi is responsible for phosphate uptake in most land plants, and the phylum is generally held to be species-poor and non-specific, with most members readily colonizing any plant species. Molecular techniques have shown both those assumptions to be unsafe, raising questions about what factors have promoted diversification in these fungi. One source of this genetic diversity may be functional diversity. 4 Specificity of the mycorrhizal interaction between plants and fungi would have important ecosystem consequences. One example would be in the control of invasiveness in introduced plant species: surprisingly, naturalized plant species in Britain are disproportionately from mycorrhizal families, suggesting that these fungi may play a role in assisting invasion. 5 What emerges from an attempt to relate biodiversity and ecosystem processes in soil is our extraordinary ignorance about the organisms involved. There are fundamental questions that are now answerable with new techniques and sufficient will, such as how biodiverse are natural soils? Do microbes have biogeography? Are there rare or even endangered microbes

Aharonov-Bohm effect in a singly connected point contact

We report the discovery of an oscillation in the low-temperature magnetoresistance of a point contact in the two-dimensional electron gas of a GaAs-AlxGa1–xAs heterostructure. The oscillation is periodic in the magnetic field and is reminiscent of the Aharonov-Bohm effect in rings, although the geometry is singly connected. A possible mechanism for this quantum interference effect is tunneling between edge states across the point contact at the potential step at the entrance and the exit of the constriction

Black holes, gravitational waves and fundamental physics: a roadmap

The grand challenges of contemporary fundamental physics—dark matter, dark energy, vacuum energy, inflation and early universe cosmology, singularities and the hierarchy problem—all involve gravity as a key component. And of all gravitational phenomena, black holes stand out in their elegant simplicity, while harbouring some of the most remarkable predictions of General Relativity: event horizons, singularities and ergoregions. The hitherto invisible landscape of the gravitational Universe is being unveiled before our eyes: the historical direct detection of gravitational waves by the LIGO-Virgo collaboration marks the dawn of a new era of scientific exploration. Gravitational-wave astronomy will allow us to test models of black hole formation, growth and evolution, as well as models of gravitational-wave generation and propagation. It will provide evidence for event horizons and ergoregions, test the theory of General Relativity itself, and may reveal the existence of new fundamental fields. The synthesis of these results has the potential to radically reshape our understanding of the cosmos and of the laws of Nature. The purpose of this work is to present a concise, yet comprehensive overview of the state of the art in the relevant fields of research, summarize important open problems, and lay out a roadmap for future progress. This write-up is an initiative taken within the framework of the European Action on 'Black holes, Gravitational waves and Fundamental Physics'

Resonant transmission through an open quantum dot

We have measured the low-temperature transport properties of a quantum dot formed in a one-dimensional channel. In zero magnetic field this device shows quantized ballistic conductance plateaus with resonant tunneling peaks in each transition region between plateaus. Studies of this structure as a function of applied perpendicular magnetic field and source-drain bias indicate that resonant structure deriving from tightly bound states is split by Coulomb charging at zero magnetic field.Comment: To be published in Phys. Rev. B (1997). 8 LaTex pages with 5 figure