네이처 컨텐츠

Editorials

Animal farm p.5

Misrepresentation of addiction by animal-rights activists should not be allowed to derail research.

doi: 10.1038/506005a

Invisible borders p.6

UK immigration rules are perceived as being tougher than they really are.

doi: 10.1038/506006a

Trick of the light p.6

The Amazon doesn’t absorb extra carbon in the dry season after all. It can become a carbon source.

doi: 10.1038/506006b

News

News Features

News & Views

A talented genus p.38

Members of a newly described candidate bacterial genus, Entotheonella, have been identified as the sources of the rich array of natural products found in the marine sponge Theonella swinhoei. Two scientists discuss this discovery from the perspectives of microbial ecology and drug discovery. See Article p.58

doi: 10.1038/nature13049

Interference identifies immune modulators p.39

A broad in vivo screen of the effects of specific gene inhibition on the antitumour activity of immune cells in mice bearing melanomas has revealed potential targets for cancer therapy. See Article p.52

doi: 10.1038/nature13050

Drought and fire change sink to source p.41

Aircraft have captured the 'breath' of the Amazon forest — carbon emissions over the Amazon basin. The findings raise concerns about the effects of future drought and call for a reassessment of how fire is used in the region. See Letter p.76

doi: 10.1038/506041a

Oiling the wheels of autoimmunity p.42

Oily substances in the skin have now been shown to contain structures that activate a population of skin-homing, self-reactive T cells. The responses of these immune cells may contribute to local defences, but also to autoimmune disease.

doi: 10.1038/506042a

Quarks are not ambidextrous p.43

By separately scattering right- and left-handed electrons off quarks in a deuterium target, researchers have improved, by about a factor of five, on a classic result of mirror-symmetry breaking from 35 years ago. See Letter p.67

doi: 10.1038/506043a

Plant diversity rooted in pathogens p.44

Ecologists have long pondered how so many species of plant can coexist locally in tropical forests. It seems that fungal pathogens have a central role, by disadvantaging species where they are locally common. See Letter p.85

doi: 10.1038/nature12851

Articles

Fifty thousand years of Arctic vegetation and megafaunal diet p.47

By analysing plant and nematode DNA from sites all around the Arctic, it is shown that vegetation before about 10,000 years ago contained more forbs (non-graminoid herbaceous vascular plants) than previously believed, which changes our understanding about the functioning of the diverse northern ecosystem that existed at this time.

doi: 10.1038/nature12921

In vivo discovery of immunotherapy targets in the tumour microenvironment p.52

A short hairpin RNA screen to identify genes that modify the action of tumour-infiltrating CD8 T cells in tumour-bearing mice pinpointed the phosphatase subunit Ppp2r2d as a new target for tumour therapy; knockdown of Ppp2r2d in T cells enabled their accumulation in tumours and significantly delayed tumour growth.

doi: 10.1038/nature12988

An environmental bacterial taxon with a large and distinct metabolic repertoire OPEN p.58

Single-cell- and metagenomics-based study reveals two members of the candidate genus ‘Entotheonella’, symbionts of the marine sponge Theonella swinhoei; distinct biosynthetic gene clusters that account for most of the bioactive polyketides and peptides known from T. swinhoei are shown to be attributable to a single member of the T. swinhoei Y microbiome.

doi: 10.1038/nature12959

Letters

A cosmic web filament revealed in Lyman-α emission around a luminous high-redshift quasar p.63

Simulations of structure formation in the Universe predict that galaxies are embedded in a ‘cosmic web’, where most baryons reside as rarefied and highly ionized gas. This material has been studied for decades in absorption against background sources, but the sparseness of these inherently one-dimensional probes preclude direct constraints on the three-dimensional morphology of the underlying web. Here we report observations of a cosmic web filament in Lyman-α emission, discovered during a survey for cosmic gas fluorescently illuminated by bright quasars at redshift z ≈ 2.3. With a linear projected size of approximately 460 physical kiloparsecs, the Lyman-α emission surrounding the radio-quiet quasar UM 287 extends well beyond the virial radius of any plausible associated dark-matter halo and therefore traces intergalactic gas. The estimated cold gas mass of the filament from the observed emission—about 1012.0 ± 0.5/C1/2 solar masses, where C is the gas clumping factor—is more than ten times larger than what is typically found in cosmological simulations, suggesting that a population of intergalactic gas clumps with subkiloparsec sizes may be missing in current numerical models.

doi: 10.1038/nature12898

Measurement of parity violation in electron–quark scattering p.67

Symmetry permeates nature and is fundamental to all laws of physics. One example is parity (mirror) symmetry, which implies that flipping left and right does not change the laws of physics. Laws for electromagnetism, gravity and the subatomic strong force respect parity symmetry, but the subatomic weak force does not. Historically, parity violation in electron scattering has been important in establishing (and now testing) the standard model of particle physics. One particular set of quantities accessible through measurements of parity-violating electron scattering are the effective weak couplings C2q, sensitive to the quarks’ chirality preference when participating in the weak force, which have been measured directly only once in the past 40 years. Here we report a measurement of the parity-violating asymmetry in electron–quark scattering, which yields a determination of 2C2u − C2d (where u and d denote up and down quarks, respectively) with a precision increased by a factor of five relative to the earlier result. These results provide evidence with greater than 95 per cent confidence that the C2q couplings are non-zero, as predicted by the electroweak theory. They lead to constraints on new parity-violating interactions beyond the standard model, particularly those due to quark chirality. Whereas contemporary particle physics research is focused on high-energy colliders such as the Large Hadron Collider, our results provide specific chirality information on electroweak theory that is difficult to obtain at high energies. Our measurement is relatively free of ambiguity in its interpretation, and opens the door to even more precise measurements in the future.

doi: 10.1038/nature12964

An optical lattice clock with accuracy and stability at the 10−18 level p.71

Progress in atomic, optical and quantum science has led to rapid improvements in atomic clocks. At the same time, atomic clock research has helped to advance the frontiers of science, affecting both fundamental and applied research. The ability to control quantum states of individual atoms and photons is central to quantum information science and precision measurement, and optical clocks based on single ions have achieved the lowest systematic uncertainty of any frequency standard. Although many-atom lattice clocks have shown advantages in measurement precision over trapped-ion clocks, their accuracy has remained 16 times worse. Here we demonstrate a many-atom system that achieves an accuracy of 6.4 × 10−18, which is not only better than a single-ion-based clock, but also reduces the required measurement time by two orders of magnitude. By systematically evaluating all known sources of uncertainty, including in situ monitoring of the blackbody radiation environment, we improve the accuracy of optical lattice clocks by a factor of 22. This single clock has simultaneously achieved the best known performance in the key characteristics necessary for consideration as a primary standard—stability and accuracy. More stable and accurate atomic clocks will benefit a wide range of fields, such as the realization and distribution of SI units, the search for time variation of fundamental constants, clock-based geodesy and other precision tests of the fundamental laws of nature. This work also connects to the development of quantum sensors and many-body quantum state engineering (such as spin squeezing) to advance measurement precision beyond the standard quantum limit.

doi: 10.1038/nature12941

Drought sensitivity of Amazonian carbon balance revealed by atmospheric measurements p.76

Feedbacks between land carbon pools and climate provide one of the largest sources of uncertainty in our predictions of global climate. Estimates of the sensitivity of the terrestrial carbon budget to climate anomalies in the tropics and the identification of the mechanisms responsible for feedback effects remain uncertain. The Amazon basin stores a vast amount of carbon, and has experienced increasingly higher temperatures and more frequent floods and droughts over the past two decades. Here we report seasonal and annual carbon balances across the Amazon basin, based on carbon dioxide and carbon monoxide measurements for the anomalously dry and wet years 2010 and 2011, respectively. We find that the Amazon basin lost 0.48 ± 0.18 petagrams of carbon per year (Pg C yr−1) during the dry year but was carbon neutral (0.06 ± 0.1 Pg C yr−1) during the wet year. Taking into account carbon losses from fire by using carbon monoxide measurements, we derived the basin net biome exchange (that is, the carbon flux between the non-burned forest and the atmosphere) revealing that during the dry year, vegetation was carbon neutral. During the wet year, vegetation was a net carbon sink of 0.25 ± 0.14 Pg C yr−1, which is roughly consistent with the mean long-term intact-forest biomass sink of 0.39 ± 0.10 Pg C yr−1 previously estimated from forest censuses. Observations from Amazonian forest plots suggest the suppression of photosynthesis during drought as the primary cause for the 2010 sink neutralization. Overall, our results suggest that moisture has an important role in determining the Amazonian carbon balance. If the recent trend of increasing precipitation extremes persists, the Amazon may become an increasing carbon source as a result of both emissions from fires and the suppression of net biome exchange by drought.

doi: 10.1038/nature12957

Convective forcing of mercury and ozone in the Arctic boundary layer induced by leads in sea ice p.81

The ongoing regime shift of Arctic sea ice from perennial to seasonal ice is associated with more dynamic patterns of opening and closing sea-ice leads (large transient channels of open water in the ice), which may affect atmospheric and biogeochemical cycles in the Arctic. Mercury and ozone are rapidly removed from the atmospheric boundary layer during depletion events in the Arctic, caused by destruction of ozone along with oxidation of gaseous elemental mercury (Hg(0)) to oxidized mercury (Hg(ii)) in the atmosphere and its subsequent deposition to snow and ice. Ozone depletion events can change the oxidative capacity of the air by affecting atmospheric hydroxyl radical chemistry, whereas atmospheric mercury depletion events can increase the deposition of mercury to the Arctic, some of which can enter ecosystems during snowmelt. Here we present near-surface measurements of atmospheric mercury and ozone from two Arctic field campaigns near Barrow, Alaska. We find that coastal depletion events are directly linked to sea-ice dynamics. A consolidated ice cover facilitates the depletion of Hg(0) and ozone, but these immediately recover to near-background concentrations in the upwind presence of open sea-ice leads. We attribute the rapid recoveries of Hg(0) and ozone to lead-initiated shallow convection in the stable Arctic boundary layer, which mixes Hg(0) and ozone from undepleted air masses aloft. This convective forcing provides additional Hg(0) to the surface layer at a time of active depletion chemistry, where it is subject to renewed oxidation. Future work will need to establish the degree to which large-scale changes in sea-ice dynamics across the Arctic alter ozone chemistry and mercury deposition in fragile Arctic ecosystems.

doi: 10.1038/nature12924

Pathogens and insect herbivores drive rainforest plant diversity and composition p.85

Tropical forests are important reservoirs of biodiversity, but the processes that maintain this diversity remain poorly understood. The Janzen–Connell hypothesis suggests that specialized natural enemies such as insect herbivores and fungal pathogens maintain high diversity by elevating mortality when plant species occur at high density (negative density dependence; NDD). NDD has been detected widely in tropical forests, but the prediction that NDD caused by insects and pathogens has a community-wide role in maintaining tropical plant diversity remains untested. We show experimentally that changes in plant diversity and species composition are caused by fungal pathogens and insect herbivores. Effective plant species richness increased across the seed-to-seedling transition, corresponding to large changes in species composition. Treating seeds and young seedlings with fungicides significantly reduced the diversity of the seedling assemblage, consistent with the Janzen–Connell hypothesis. Although suppressing insect herbivores using insecticides did not alter species diversity, it greatly increased seedling recruitment and caused a marked shift in seedling species composition. Overall, seedling recruitment was significantly reduced at high conspecific seed densities and this NDD was greatest for the species that were most abundant as seeds. Suppressing fungi reduced the negative effects of density on recruitment, confirming that the diversity-enhancing effect of fungi is mediated by NDD. Our study provides an overall test of the Janzen–Connell hypothesis and demonstrates the crucial role that insects and pathogens have both in structuring tropical plant communities and in maintaining their remarkable diversity.

doi: 10.1038/nature12911

Three keys to the radiation of angiosperms into freezing environments p.89

Early flowering plants are thought to have been woody species restricted to warm habitats. This lineage has since radiated into almost every climate, with manifold growth forms. As angiosperms spread and climate changed, they evolved mechanisms to cope with episodic freezing. To explore the evolution of traits underpinning the ability to persist in freezing conditions, we assembled a large species-level database of growth habit (woody or herbaceous; 49,064 species), as well as leaf phenology (evergreen or deciduous), diameter of hydraulic conduits (that is, xylem vessels and tracheids) and climate occupancies (exposure to freezing). To model the evolution of species’ traits and climate occupancies, we combined these data with an unparalleled dated molecular phylogeny (32,223 species) for land plants. Here we show that woody clades successfully moved into freezing-prone environments by either possessing transport networks of small safe conduits and/or shutting down hydraulic function by dropping leaves during freezing. Herbaceous species largely avoided freezing periods by senescing cheaply constructed aboveground tissue. Growth habit has long been considered labile, but we find that growth habit was less labile than climate occupancy. Additionally, freezing environments were largely filled by lineages that had already become herbs or, when remaining woody, already had small conduits (that is, the trait evolved before the climate occupancy). By contrast, most deciduous woody lineages had an evolutionary shift to seasonally shedding their leaves only after exposure to freezing (that is, the climate occupancy evolved before the trait). For angiosperms to inhabit novel cold environments they had to gain new structural and functional trait solutions; our results suggest that many of these solutions were probably acquired before their foray into the cold.

doi: 10.1038/nature12872

Modelling the effects of subjective and objective decision making in scientific peer review p.93

The objective of science is to advance knowledge, primarily in two interlinked ways: circulating ideas, and defending or criticizing the ideas of others. Peer review acts as the gatekeeper to these mechanisms. Given the increasing concern surrounding the reproducibility of much published research, it is critical to understand whether peer review is intrinsically susceptible to failure, or whether other extrinsic factors are responsible that distort scientists’ decisions. Here we show that even when scientists are motivated to promote the truth, their behaviour may be influenced, and even dominated, by information gleaned from their peers’ behaviour, rather than by their personal dispositions. This phenomenon, known as herding, subjects the scientific community to an inherent risk of converging on an incorrect answer and raises the possibility that, under certain conditions, science may not be self-correcting. We further demonstrate that exercising some subjectivity in reviewer decisions, which serves to curb the herding process, can be beneficial for the scientific community in processing available information to estimate truth more accurately. By examining the impact of different models of reviewer decisions on the dynamic process of publication, and thereby on eventual aggregation of knowledge, we provide a new perspective on the ongoing discussion of how the peer-review process may be improved.

doi: 10.1038/nature12786

Sequence variants in SLC16A11 are a common risk factor for type 2 diabetes in Mexico p.97

Performing genetic studies in multiple human populations can identify disease risk alleles that are common in one population but rare in others, with the potential to illuminate pathophysiology, health disparities, and the population genetic origins of disease alleles. Here we analysed 9.2 million single nucleotide polymorphisms (SNPs) in each of 8,214 Mexicans and other Latin Americans: 3,848 with type 2 diabetes and 4,366 non-diabetic controls. In addition to replicating previous findings, we identified a novel locus associated with type 2 diabetes at genome-wide significance spanning the solute carriers SLC16A11 and SLC16A13 (P = 3.9 × 10−13; odds ratio (OR) = 1.29). The association was stronger in younger, leaner people with type 2 diabetes, and replicated in independent samples (P = 1.1 × 10−4; OR = 1.20). The risk haplotype carries four amino acid substitutions, all in SLC16A11; it is present at ∼50% frequency in Native American samples and ∼10% in east Asian, but is rare in European and African samples. Analysis of an archaic genome sequence indicated that the risk haplotype introgressed into modern humans via admixture with Neanderthals. The SLC16A11 messenger RNA is expressed in liver, and V5-tagged SLC16A11 protein localizes to the endoplasmic reticulum. Expression of SLC16A11 in heterologous cells alters lipid metabolism, most notably causing an increase in intracellular triacylglycerol levels. Despite type 2 diabetes having been well studied by genome-wide association studies in other populations, analysis in Mexican and Latin American individuals identified SLC16A11 as a novel candidate gene for type 2 diabetes with a possible role in triacylglycerol metabolism.

doi: 10.1038/nature12828

Structure of the SecY channel during initiation of protein translocation p.102

Many secretory proteins are targeted by signal sequences to a protein-conducting channel, formed by prokaryotic SecY or eukaryotic Sec61 complexes, and are translocated across the membrane during their synthesis. Crystal structures of the inactive channel show that the SecY subunit of the heterotrimeric complex consists of two halves that form an hourglass-shaped pore with a constriction in the middle of the membrane and a lateral gate that faces the lipid phase. The closed channel has an empty cytoplasmic funnel and an extracellular funnel that is filled with a small helical domain, called the plug. During initiation of translocation, a ribosome–nascent chain complex binds to the SecY (or Sec61) complex, resulting in insertion of the nascent chain. However, the mechanism of channel opening during translocation is unclear. Here we have addressed this question by determining structures of inactive and active ribosome–channel complexes with cryo-electron microscopy. Non-translating ribosome–SecY channel complexes derived from Methanocaldococcus jannaschii or Escherichia coli show the channel in its closed state, and indicate that ribosome binding per se causes only minor changes. The structure of an active E. coli ribosome–channel complex demonstrates that the nascent chain opens the channel, causing mostly rigid body movements of the amino- and carboxy-terminal halves of SecY. In this early translocation intermediate, the polypeptide inserts as a loop into the SecY channel with the hydrophobic signal sequence intercalated into the open lateral gate. The nascent chain also forms a loop on the cytoplasmic surface of SecY rather than entering the channel directly.

doi: 10.1038/nature12720

Structures of the Sec61 complex engaged in nascent peptide translocation or membrane insertion p.107

The biogenesis of secretory as well as transmembrane proteins requires the activity of the universally conserved protein-conducting channel (PCC), the Sec61 complex (SecY complex in bacteria). In eukaryotic cells the PCC is located in the membrane of the endoplasmic reticulum where it can bind to translating ribosomes for co-translational protein transport. The Sec complex consists of three subunits (Sec61α, β and γ) and provides an aqueous environment for the translocation of hydrophilic peptides as well as a lateral opening in the Sec61α subunit that has been proposed to act as a gate for the membrane partitioning of hydrophobic domains. A plug helix and a so-called pore ring are believed to seal the PCC against ion flow and are proposed to rearrange for accommodation of translocating peptides. Several crystal and cryo-electron microscopy structures revealed different conformations of closed and partially open Sec61 and SecY complexes. However, in none of these samples has the translocation state been unambiguously defined biochemically. Here we present cryo-electron microscopy structures of ribosome-bound Sec61 complexes engaged in translocation or membrane insertion of nascent peptides. Our data show that a hydrophilic peptide can translocate through the Sec complex with an essentially closed lateral gate and an only slightly rearranged central channel. Membrane insertion of a hydrophobic domain seems to occur with the Sec complex opening the proposed lateral gate while rearranging the plug to maintain an ion permeability barrier. Taken together, we provide a structural model for the basic activities of the Sec61 complex as a protein-conducting channel.

doi: 10.1038/nature12950

Aprataxin resolves adenylated RNA–DNA junctions to maintain genome integrity p.111

Faithful maintenance and propagation of eukaryotic genomes is ensured by three-step DNA ligation reactions used by ATP-dependent DNA ligases. Paradoxically, when DNA ligases encounter nicked DNA structures with abnormal DNA termini, DNA ligase catalytic activity can generate and/or exacerbate DNA damage through abortive ligation that produces chemically adducted, toxic 5′-adenylated (5′-AMP) DNA lesions. Aprataxin (APTX) reverses DNA adenylation but the context for deadenylation repair is unclear. Here we examine the importance of APTX to RNase-H2-dependent excision repair (RER) of a lesion that is very frequently introduced into DNA, a ribonucleotide. We show that ligases generate adenylated 5′ ends containing a ribose characteristic of RNase H2 incision. APTX efficiently repairs adenylated RNA–DNA, and acting in an RNA–DNA damage response (RDDR), promotes cellular survival and prevents S-phase checkpoint activation in budding yeast undergoing RER. Structure–function studies of human APTX–RNA–DNA–AMP–Zn complexes define a mechanism for detecting and reversing adenylation at RNA–DNA junctions. This involves A-form RNA binding, proper protein folding and conformational changes, all of which are affected by heritable APTX mutations in ataxia with oculomotor apraxia 1. Together, these results indicate that accumulation of adenylated RNA–DNA may contribute to neurological disease.

doi: 10.1038/nature12824

Crystal structures of the Lsm complex bound to the 3′ end sequence of U6 small nuclear RNA p.116

Splicing of precursor messenger RNA (pre-mRNA) in eukaryotic cells is carried out by the spliceosome, which consists of five small nuclear ribonucleoproteins (snRNPs) and a number of accessory factors and enzymes. Each snRNP contains a ring-shaped subcomplex of seven proteins and a specific RNA molecule. The U6 snRNP contains a unique heptameric Lsm protein complex, which specifically recognizes the U6 small nuclear RNA at its 3′ end. Here we report the crystal structures of the heptameric Lsm complex, both by itself and in complex with a 3′ fragment of U6 snRNA, at 2.8 Å resolution. Each of the seven Lsm proteins interacts with two neighbouring Lsm components to form a doughnut-shaped assembly, with the order Lsm3–2–8–4–7–5–6. The four uridine nucleotides at the 3′ end of U6 snRNA are modularly recognized by Lsm3, Lsm2, Lsm8 and Lsm4, with the uracil base specificity conferred by a highly conserved asparagine residue. The uracil base at the extreme 3′ end is sandwiched by His 36 and Arg 69 from Lsm3, through π–π and cation–π interactions, respectively. The distinctive end-recognition of U6 snRNA by the Lsm complex contrasts with RNA binding by the Sm complex in the other snRNPs. The structural features and associated biochemical analyses deepen mechanistic understanding of the U6 snRNP function in pre-mRNA splicing.

doi: 10.1038/nature12803