Understanding the evolutionary transformation of fish fins into tetrapod limbs is a fundamental problem in biology. The search for antecedents of tetrapod digits in fish has remained controversial because the distal skeletons of limbs and fins differ structurally, developmentally, and histologically. Moreover, comparisons of fins with limbs have been limited by a relative paucity of data on the cellular and molecular processes underlying the development of the fin skeleton. Here, we provide a functional analysis, using CRISPR/Cas9 and fate mapping, of 5' hox genes and enhancers in zebrafish that are indispensable for the development of the wrists and digits of tetrapods. We show that cells marked by the activity of an autopodial hoxa13 enhancer exclusively form elements of the fin fold, including the osteoblasts of the dermal rays. In hox13 knockout fish, we find that a marked reduction and loss of fin rays is associated with an increased number of endochondral distal radials. These discoveries reveal a cellular and genetic connection between the fin rays of fish and the digits of tetrapods and suggest that digits originated via the transition of distal cellular fates.

Hypermethylation of the promoters of tumour suppressor genes represses transcription of these genes, conferring growth advantages to cancer cells. How these changes arise is poorly understood. Here we show that the activity of oxygen-dependent ten-eleven translocation (TET) enzymes is reduced by tumour hypoxia in human and mouse cells. TET enzymes catalyse DNA demethylation through 5-methylcytosine oxidation. This reduction in activity occurs independently of hypoxia-associated alterations in TET expression, proliferation, metabolism, hypoxia-inducible factor activity or reactive oxygen species, and depends directly on oxygen shortage. Hypoxia-induced loss of TET activity increases hypermethylation at gene promoters in vitro. In patients, tumour suppressor gene promoters are markedly more methylated in hypoxic tumour tissue, independent of proliferation, stromal cell infiltration and tumour characteristics. Our data suggest that up to half of hypermethylation events are due to hypoxia, with these events conferring a selective advantage. Accordingly, increased hypoxia in mouse breast tumours increases hypermethylation, while restoration of tumour oxygenation abrogates this effect. Tumour hypoxia therefore acts as a novel regulator of DNA methylation.

Many experiments have shown that loss of biodiversity reduces the capacity of ecosystems to provide the multiple services on which humans depend. However, experiments necessarily simplify the complexity of natural ecosystems and will normally control for other important drivers of ecosystem functioning, such as the environment or land use. In addition, existing studies typically focus on the diversity of single trophic groups, neglecting the fact that biodiversity loss occurs across many taxa and that the functional effects of any trophic group may depend on the abundance and diversity of others. Here we report analysis of the relationships between the species richness and abundance of nine trophic groups, including 4,600 above- and below-ground taxa, and 14 ecosystem services and functions and with their simultaneous provision (or multifunctionality) in 150 grasslands. We show that high species richness in multiple trophic groups (multitrophic richness) had stronger positive effects on ecosystem services than richness in any individual trophic group; this includes plant species richness, the most widely used measure of biodiversity. On average, three trophic groups influenced each ecosystem service, with each trophic group influencing at least one service. Multitrophic richness was particularly beneficial for 'regulating' and 'cultural' services, and for multifunctionality, whereas a change in the total abundance of species or biomass in multiple trophic groups (the multitrophic abundance) positively affected supporting services. Multitrophic richness and abundance drove ecosystem functioning as strongly as abiotic conditions and land-use intensity, extending previous experimental results to real-world ecosystems. Primary producers, herbivorous insects and microbial decomposers seem to be particularly important drivers of ecosystem functioning, as shown by the strong and frequent positive associations of their richness or abundance with multiple ecosystem services. Our results show that multitrophic richness and abundance support ecosystem functioning, and demonstrate that a focus on single groups has led to researchers to greatly underestimate the functional importance of biodiversity.

Cataclysmic variable stars-novae, dwarf novae, and nova-likes-are close binary systems consisting of a white dwarf star (the primary) that is accreting matter from a low-mass companion star (the secondary). From time to time such systems undergo large-amplitude brightenings. The most spectacular eruptions, with a ten-thousandfold increase in brightness, occur in classical novae and are caused by a thermonuclear runaway on the surface of the white dwarf. Such eruptions are thought to recur on timescales of ten thousand to a million years. In between, the system's properties depend primarily on the mass-transfer rate: if it is lower than a billionth of a solar mass per year, the accretion becomes unstable and the matter is dumped onto the white dwarf during quasi-periodic dwarf nova outbursts. The hibernation hypothesis predicts that nova eruptions strongly affect the mass-transfer rate in the binary, keeping it high for centuries after the event. Subsequently, the mass-transfer rate should significantly decrease for a thousand to a million years, starting the hibernation phase. After that the nova awakes again-with accretion returning to the pre-eruption level and leading to a new nova explosion. The hibernation model predicts cyclical evolution of cataclysmic variables through phases of high and low mass-transfer. The theory gained some support from the discovery of ancient nova shells around the dwarf novae Z Camelopardalis and AT Cancri, but direct evidence for considerable mass-transfer changes prior, during and after nova eruptions has not hitherto been found. Here we report long-term observations of the classical nova V1213 Cen (Nova Centauri 2009) covering its pre- and post-eruption phases and precisely documenting its evolution. Within the six years before the explosion, the system revealed dwarf nova outbursts indicative of a low mass-transfer rate. The post-nova is two orders of magnitude brighter than the pre-nova at minimum light with no trace of dwarf nova behaviour, implying that the mass-transfer rate increased considerably as a result of the nova explosion.

Thermally activated ion channels are known to detect the entire thermal range from extreme heat (TRPV2), painful heat (TRPV1, TRPM3 and ANO1), non-painful warmth (TRPV3 and TRPV4) and non-painful coolness (TRPM8) through to painful cold (TRPA1). Genetic deletion of each of these ion channels, however, has only modest effects on thermal behaviour in mice, with the exception of TRPM8, the deletion of which has marked effects on the perception of moderate coolness in the range 10-25 °C. The molecular mechanism responsible for detecting non-painful warmth, in particular, is unresolved. Here we used calcium imaging to identify a population of thermally sensitive somatosensory neurons which do not express any of the known thermally activated TRP channels. We then used a combination of calcium imaging, electrophysiology and RNA sequencing to show that the ion channel generating heat sensitivity in these neurons is TRPM2. Autonomic neurons, usually thought of as exclusively motor, also express TRPM2 and respond directly to heat. Mice in which TRPM2 had been genetically deleted showed a striking deficit in their sensation of non-noxious warm temperatures, consistent with the idea that TRPM2 initiates a 'warm' signal which drives cool-seeking behaviour.

Viruses are the most abundant biological entities on Earth, but challenges in detecting, isolating, and classifying unknown viruses have prevented exhaustive surveys of the global virome. Here we analysed over 5 Tb of metagenomic sequence data from 3,042 geographically diverse samples to assess the global distribution, phylogenetic diversity, and host specificity of viruses. We discovered over 125,000 partial DNA viral genomes, including the largest phage yet identified, and increased the number of known viral genes by 16-fold. Half of the predicted partial viral genomes were clustered into genetically distinct groups, most of which included genes unrelated to those in known viruses. Using CRISPR spacers and transfer RNA matches to link viral groups to microbial host(s), we doubled the number of microbial phyla known to be infected by viruses, and identified viruses that can infect organisms from different phyla. Analysis of viral distribution across diverse ecosystems revealed strong habitat-type specificity for the vast majority of viruses, but also identified some cosmopolitan groups. Our results highlight an extensive global viral diversity and provide detailed insight into viral habitat distribution and host–virus interactions.