Volume 502 Issue 7473


All together now p.593

Online discussion is an essential aspect of the post-publication review of findings.

doi: 10.1038/502593a

Time to talk p.593

Proposals to bring hydrofluorocarbons under the auspices of the Montreal Protocol provide a simple test of the international community’s commitment to tackling climate change.

doi: 10.1038/502593b

Playful paradoxes p.594

A half-century of Doctor Who has shown the dramatic possibilities of science in the arts.

doi: 10.1038/502594a



Southern star p.608

Can the Southern African Large Telescope live up to its potential?

doi: 10.1038/502608a

Lady of the lakes p.612

Diane Orihel set her PhD aside to lead a massive protest when Canada tried to shut down its unique Experimental Lakes Area.

doi: 10.1038/502612a

News & Views

Drivers of decoupling in drylands p.628

A study reveals that increasing aridity alters the balance of carbon, nitrogen and phosphorus in dryland soils, providing insight into how global climate change will affect soil fertility and ecosystem services. See Letter p.672

doi: 10.1038/502628a

Pivotal findings for a transcription machine p.629

Crystal structures of the complete RNA polymerase I complex are now revealed. The structures link the opening and closing of this enzyme's DNA-binding cleft to the control of transcription. See Articles p.644 & p.650

doi: 10.1038/nature12700

Single electrons pop out of the Fermi sea p.630

The ability to control individual electrons in an electronic conductor would pave the way for novel quantum technologies. Single electrons emerging from a sea of their fellows in a nanoscale electrode can now be generated. See Letter p.659

doi: 10.1038/nature12699

Rough passage across a barrier p.632

The dynamics of chemical reactions in solution are described by Kramers' theory, but the parameters involved have eluded direct measurement. A study of protein folding reveals how this problem can be overcome. See Letter p.685

doi: 10.1038/nature12697

The data gap p.633

A comprehensive search identifies a global dearth of data on the generation, treatment and use of wastewater. Remedying this situation will help policy-makers to better legislate for the management of this precious resource.

doi: 10.1038/502633a

Coral animals combat stress with sulphur p.634

Photosynthetic algal symbionts of corals produce sulphur substances that are involved in the regulation of ocean temperatures. In a twist to the tale, it emerges that coral animals produce the same compounds. See Letter p.677

doi: 10.1038/nature12698


Arteriolar niches maintain haematopoietic stem cell quiescence p.637

Immunofluorescence imaging and computational modelling are used to study the spatial distribution of different cell types within the haematopoietic stem cell (HSC) niche; findings show that quiescent HSCs associate specifically with small arterioles that are preferentially found in the endosteal bone marrow and are essential in maintaining this quiescence.

doi: 10.1038/nature12612

Crystal structure of the 14-subunit RNA polymerase I p.644

RNA polymerase (Pol) I transcribes ribosomal RNA that is critically required for ribosome assembly, and the enzyme is a major determinant of protein biosynthesis and cell growth; here the crystal structure of the complete 14-subunit Pol I from yeast is determined, providing insights into its unique architecture and the possible functional roles of its components.

doi: 10.1038/nature12636


A uniform metal distribution in the intergalactic medium of the Perseus cluster of galaxies p.656

Most of the metals (elements heavier than helium) produced by stars in the member galaxies of clusters currently reside within the hot, X-ray-emitting intra-cluster gas. Observations of X-ray line emission from this intergalactic medium have suggested a relatively small cluster-to-cluster scatter outside the cluster centres and enrichment with iron out to large radii, leading to the idea that the metal enrichment occurred early in the history of the Universe. Models with early enrichment predict a uniform metal distribution at large radii in clusters, whereas those with late-time enrichment are expected to introduce significant spatial variations of the metallicity. To discriminate clearly between these competing models, it is essential to test for potential inhomogeneities by measuring the abundances out to large radii along multiple directions in clusters, which has not hitherto been done. Here we report a remarkably uniform iron abundance, as a function of radius and azimuth, that is statistically consistent with a constant value of ZFe = 0.306 ± 0.012 in solar units out to the edge of the nearby Perseus cluster. This homogeneous distribution requires that most of the metal enrichment of the intergalactic medium occurred before the cluster formed, probably more than ten billion years ago, during the period of maximal star formation and black hole activity.

doi: 10.1038/nature12646

Minimal-excitation states for electron quantum optics using levitons p.659

The on-demand generation of pure quantum excitations is important for the operation of quantum systems, but it is particularly difficult for a system of fermions. This is because any perturbation affects all states below the Fermi energy, resulting in a complex superposition of particle and hole excitations. However, it was predicted nearly 20 years ago that a Lorentzian time-dependent potential with quantized flux generates a minimal excitation with only one particle and no hole. Here we report that such quasiparticles (hereafter termed levitons) can be generated on demand in a conductor by applying voltage pulses to a contact. Partitioning the excitations with an electronic beam splitter generates a current noise that we use to measure their number. Minimal-excitation states are observed for Lorentzian pulses, whereas for other pulse shapes there are significant contributions from holes. Further identification of levitons is provided in the energy domain with shot-noise spectroscopy, and in the time domain with electronic Hong–Ou–Mandel noise correlations. The latter, obtained by colliding synchronized levitons on a beam splitter, exemplifies the potential use of levitons for quantum information: using linear electron quantum optics in ballistic conductors, it is possible to imagine flying-qubit operation in which the Fermi statistics are exploited to entangle synchronized electrons emitted by distinct sources. Compared with electron sources based on quantum dots, the generation of levitons does not require delicate nanolithography, considerably simplifying the circuitry for scalability. Levitons are not limited to carrying a single charge, and so in a broader context n-particle levitons could find application in the study of full electron counting statistics. But they can also carry a fraction of charge if they are implemented in Luttinger liquids or in fractional quantum Hall edge channels; this allows the study of Abelian and non-Abelian quasiparticles in the time domain. Finally, the generation technique could be applied to cold atomic gases, leading to the possibility of atomic levitons.

doi: 10.1038/nature12713

Coupling a single electron to a Bose–Einstein condensate p.664

The coupling of electrons to matter lies at the heart of our understanding of material properties such as electrical conductivity. Electron–phonon coupling can lead to the formation of a Cooper pair out of two repelling electrons, which forms the basis for Bardeen–Cooper–Schrieffer superconductivity. Here we study the interaction of a single localized electron with a Bose–Einstein condensate and show that the electron can excite phonons and eventually trigger a collective oscillation of the whole condensate. We find that the coupling is surprisingly strong compared to that of ionic impurities, owing to the more favourable mass ratio. The electron is held in place by a single charged ionic core, forming a Rydberg bound state. This Rydberg electron is described by a wavefunction extending to a size of up to eight micrometres, comparable to the dimensions of the condensate. In such a state, corresponding to a principal quantum number of n = 202, the Rydberg electron is interacting with several tens of thousands of condensed atoms contained within its orbit. We observe surprisingly long lifetimes and finite size effects caused by the electron exploring the outer regions of the condensate. We anticipate future experiments on electron orbital imaging, the investigation of phonon-mediated coupling of single electrons, and applications in quantum optics.

doi: 10.1038/nature12592

Gradual demise of a thin southern Laurentide ice sheet recorded by Mississippi drainage p.668

At the Last Glacial Maximum (LGM), about 21,000 years before present, land-based ice sheets held enough water to reduce global mean sea level by 130 metres. Yet after decades of study, major uncertainties remain as to the distribution of that ice. Here we test four reconstructions of North American deglacial ice-sheet history by quantitatively connecting them to high-resolution oxygen isotope (δ18O) records from the Gulf of Mexico using a water mixing model. For each reconstruction, we route meltwater and seasonal runoff through the time-evolving Mississippi drainage basin, which co-evolves with ice geometry and changing topography as ice loads deform the solid Earth and produce spatially variable sea level in a process known as glacial isostatic adjustment. The δ18O records show that the Mississippi-drained southern Laurentide ice sheet contributed only 5.4 ± 2.1 metres to global sea level rise, of which 0.66 ± 0.07 metres were released during the meltwater pulse 1A event 14,650–14,310 years before present, far less water than previously thought. In contrast, the three reconstructions based on glacial isostatic adjustment overpredict the δ18O-based post-LGM meltwater volume by a factor of 1.6 to 3.6. The fourth reconstruction, which is based on ice physics, has a low enough Mississippi-routed meltwater discharge to be consistent with δ18O constraints, but also contains the largest LGM North American ice volume. This suggests that modelling based on ice physics may be the best way of matching isotopic records while also sequestering enough water in the North American ice sheets to match the observed LGM sea level fall.

doi: 10.1038/nature12609

Decoupling of soil nutrient cycles as a function of aridity in global drylands p.672

The biogeochemical cycles of carbon (C), nitrogen (N) and phosphorus (P) are interlinked by primary production, respiration and decomposition in terrestrial ecosystems. It has been suggested that the C, N and P cycles could become uncoupled under rapid climate change because of the different degrees of control exerted on the supply of these elements by biological and geochemical processes. Climatic controls on biogeochemical cycles are particularly relevant in arid, semi-arid and dry sub-humid ecosystems (drylands) because their biological activity is mainly driven by water availability. The increase in aridity predicted for the twenty-first century in many drylands worldwide may therefore threaten the balance between these cycles, differentially affecting the availability of essential nutrients. Here we evaluate how aridity affects the balance between C, N and P in soils collected from 224 dryland sites from all continents except Antarctica. We find a negative effect of aridity on the concentration of soil organic C and total N, but a positive effect on the concentration of inorganic P. Aridity is negatively related to plant cover, which may favour the dominance of physical processes such as rock weathering, a major source of P to ecosystems, over biological processes that provide more C and N, such as litter decomposition. Our findings suggest that any predicted increase in aridity with climate change will probably reduce the concentrations of N and C in global drylands, but increase that of P. These changes would uncouple the C, N and P cycles in drylands and could negatively affect the provision of key services provided by these ecosystems.

doi: 10.1038/nature12670

DMSP biosynthesis by an animal and its role in coral thermal stress response p.677

Globally, reef-building corals are the most prolific producers of dimethylsulphoniopropionate (DMSP), a central molecule in the marine sulphur cycle and precursor of the climate-active gas dimethylsulphide. At present, DMSP production by corals is attributed entirely to their algal endosymbiont, Symbiodinium. Combining chemical, genomic and molecular approaches, we show that coral juveniles produce DMSP in the absence of algal symbionts. DMSP levels increased up to 54% over time in newly settled coral juveniles lacking algal endosymbionts, and further increases, up to 76%, were recorded when juveniles were subjected to thermal stress. We uncovered coral orthologues of two algal genes recently identified in DMSP biosynthesis, strongly indicating that corals possess the enzymatic machinery necessary for DMSP production. Our results overturn the paradigm that photosynthetic organisms are the sole biological source of DMSP, and highlight the double jeopardy represented by worldwide declining coral cover, as the potential to alleviate thermal stress through coral-produced DMSP declines correspondingly.

doi: 10.1038/nature12677

Structural insight into magnetochrome-mediated magnetite biomineralization p.681

Magnetotactic bacteria align along the Earth’s magnetic field using an organelle called the magnetosome, a biomineralized magnetite (Fe(ii)Fe(iii)2O4) or greigite (Fe(ii)Fe(iii)2S4) crystal embedded in a lipid vesicle. Although the need for both iron(ii) and iron(iii) is clear, little is known about the biological mechanisms controlling their ratio. Here we present the structure of the magnetosome-associated protein MamP and find that it is built on a unique arrangement of a self-plugged PDZ domain fused to two magnetochrome domains, defining a new class of c-type cytochrome exclusively found in magnetotactic bacteria. Mutational analysis, enzyme kinetics, co-crystallization with iron(ii) and an in vitro MamP-assisted magnetite production assay establish MamP as an iron oxidase that contributes to the formation of iron(iii) ferrihydrite eventually required for magnetite crystal growth in vivo. These results demonstrate the molecular mechanisms of iron management taking place inside the magnetosome and highlight the role of magnetochrome in iron biomineralization.

doi: 10.1038/nature12573

Single-molecule fluorescence probes dynamics of barrier crossing p.685

Kramers developed the theory on how chemical reaction rates are influenced by the viscosity of the medium. At the viscosity of water, the kinetics of unimolecular reactions are described by diffusion of a Brownian particle over a free-energy barrier separating reactants and products. For reactions in solution this famous theory extended Eyring’s transition state theory, and is widely applied in physics, chemistry and biology, including to reactions as complex as protein folding. Because the diffusion coefficient of Kramers’ theory is determined by the dynamics in the sparsely populated region of the barrier top, its properties have not been directly measured for any molecular system. Here we show that the Kramers diffusion coefficient and free-energy barrier can be characterized by measuring the temperature- and viscosity-dependence of the transition path time for protein folding. The transition path is the small fraction of an equilibrium trajectory for a single molecule when the free-energy barrier separating two states is actually crossed. Its duration, the transition path time, can now be determined from photon trajectories for single protein molecules undergoing folding/unfolding transitions. Our finding of a long transition path time with an unusually small solvent viscosity dependence suggests that internal friction as well as solvent friction determine the Kramers diffusion coefficient for α-helical proteins, as opposed to a breakdown of his theory, which occurs for many small-molecule reactions. It is noteworthy that the new and fundamental information concerning Kramers’ theory and the dynamics of barrier crossings obtained here come from experiments on a protein rather than a much simpler chemical or physical system.

doi: 10.1038/nature12649

Photosynthetic entrainment of the Arabidopsis thaliana circadian clock p.689

Circadian clocks provide a competitive advantage in an environment that is heavily influenced by the rotation of the Earth, by driving daily rhythms in behaviour, physiology and metabolism in bacteria, fungi, plants and animals. Circadian clocks comprise transcription–translation feedback loops, which are entrained by environmental signals such as light and temperature to adjust the phase of rhythms to match the local environment. The production of sugars by photosynthesis is a key metabolic output of the circadian clock in plants. Here we show that these rhythmic, endogenous sugar signals can entrain circadian rhythms in Arabidopsis thaliana by regulating the gene expression of circadian clock components early in the photoperiod, thus defining a ‘metabolic dawn’. By inhibiting photosynthesis, we demonstrate that endogenous oscillations in sugar levels provide metabolic feedback to the circadian oscillator through the morning-expressed gene PSEUDO-RESPONSE REGULATOR 7 (PRR7), and we identify that prr7 mutants are insensitive to the effects of sucrose on the circadian period. Thus, photosynthesis has a marked effect on the entrainment and maintenance of robust circadian rhythms in A. thaliana, demonstrating that metabolism has a crucial role in regulation of the circadian clock.

doi: 10.1038/nature12603

Synthetic non-oxidative glycolysis enables complete carbon conservation p.693

Glycolysis, or its variations, is a fundamental metabolic pathway in life that functions in almost all organisms to decompose external or intracellular sugars. The pathway involves the partial oxidation and splitting of sugars to pyruvate, which in turn is decarboxylated to produce acetyl-coenzyme A (CoA) for various biosynthetic purposes. The decarboxylation of pyruvate loses a carbon equivalent, and limits the theoretical carbon yield to only two moles of two-carbon (C2) metabolites per mole of hexose. This native route is a major source of carbon loss in biorefining and microbial carbon metabolism. Here we design and construct a non-oxidative, cyclic pathway that allows the production of stoichiometric amounts of C2 metabolites from hexose, pentose and triose phosphates without carbon loss. We tested this pathway, termed non-oxidative glycolysis (NOG), in vitro and in vivo in Escherichia coli. NOG enables complete carbon conservation in sugar catabolism to acetyl-CoA, and can be used in conjunction with CO2 fixation and other one-carbon (C1) assimilation pathways to achieve a 100% carbon yield to desirable fuels and chemicals.

doi: 10.1038/nature12575

Discovery of new enzymes and metabolic pathways by using structure and genome context p.698

Assigning valid functions to proteins identified in genome projects is challenging: overprediction and database annotation errors are the principal concerns. We and others are developing computation-guided strategies for functional discovery with ‘metabolite docking’ to experimentally derived or homology-based three-dimensional structures. Bacterial metabolic pathways often are encoded by ‘genome neighbourhoods’ (gene clusters and/or operons), which can provide important clues for functional assignment. We recently demonstrated the synergy of docking and pathway context by ‘predicting’ the intermediates in the glycolytic pathway in Escherichia coli. Metabolite docking to multiple binding proteins and enzymes in the same pathway increases the reliability of in silico predictions of substrate specificities because the pathway intermediates are structurally similar. Here we report that structure-guided approaches for predicting the substrate specificities of several enzymes encoded by a bacterial gene cluster allowed the correct prediction of the in vitro activity of a structurally characterized enzyme of unknown function (PDB 2PMQ), 2-epimerization of trans-4-hydroxy-l-proline betaine (tHyp-B) and cis-4-hydroxy-d-proline betaine (cHyp-B), and also the correct identification of the catabolic pathway in which Hyp-B 2-epimerase participates. The substrate-liganded pose predicted by virtual library screening (docking) was confirmed experimentally. The enzymatic activities in the predicted pathway were confirmed by in vitro assays and genetic analyses; the intermediates were identified by metabolomics; and repression of the genes encoding the pathway by high salt concentrations was established by transcriptomics, confirming the osmolyte role of tHyp-B. This study establishes the utility of structure-guided functional predictions to enable the discovery of new metabolic pathways.

doi: 10.1038/nature12576

Meiotic chromosome structures constrain and respond to designation of crossover sites p.703

Crossover recombination events between homologous chromosomes are required to form chiasmata, temporary connections between homologues that ensure their proper segregation at meiosis I. Despite this requirement for crossovers and an excess of the double-strand DNA breaks that are the initiating events for meiotic recombination, most organisms make very few crossovers per chromosome pair. Moreover, crossovers tend to inhibit the formation of other crossovers nearby on the same chromosome pair, a poorly understood phenomenon known as crossover interference. Here we show that the synaptonemal complex, a meiosis-specific structure that assembles between aligned homologous chromosomes, both constrains and is altered by crossover recombination events. Using a cytological marker of crossover sites in Caenorhabditis elegans, we show that partial depletion of the synaptonemal complex central region proteins attenuates crossover interference, increasing crossovers and reducing the effective distance over which interference operates, indicating that synaptonemal complex proteins limit crossovers. Moreover, we show that crossovers are associated with a local 0.4–0.5-micrometre increase in chromosome axis length. We propose that meiotic crossover regulation operates as a self-limiting system in which meiotic chromosome structures establish an environment that promotes crossover formation, which in turn alters chromosome structure to inhibit other crossovers at additional sites.

doi: 10.1038/nature12577

Visualizing virus assembly intermediates inside marine cyanobacteria p.707

Cyanobacteria are photosynthetic organisms responsible for ∼25% of organic carbon fixation on the Earth. These bacteria began to convert solar energy and carbon dioxide into bioenergy and oxygen more than two billion years ago. Cyanophages, which infect these bacteria, have an important role in regulating the marine ecosystem by controlling cyanobacteria community organization and mediating lateral gene transfer. Here we visualize the maturation process of cyanophage Syn5 inside its host cell, Synechococcus, using Zernike phase contrast electron cryo-tomography (cryoET). This imaging modality yields dramatic enhancement of image contrast over conventional cryoET and thus facilitates the direct identification of subcellular components, including thylakoid membranes, carboxysomes and polyribosomes, as well as phages, inside the congested cytosol of the infected cell. By correlating the structural features and relative abundance of viral progeny within cells at different stages of infection, we identify distinct Syn5 assembly intermediates. Our results indicate that the procapsid releases scaffolding proteins and expands its volume at an early stage of genome packaging. Later in the assembly process, we detected full particles with a tail either with or without an additional horn. The morphogenetic pathway we describe here is highly conserved and was probably established long before that of double-stranded DNA viruses infecting more complex organisms.

doi: 10.1038/nature12604