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Whole genome sequences enable discovery of rare variants which may help to explain the heritability of common diseases. Here the authors find that ultra-rare variants explain ~50% of coronary artery disease (CAD) heritability and highlight several functional processes including cell type-specific regulatory mechanisms as key drivers of CAD genetic risk.

Data from a variety of sources—including satellite, climate and soil data, as well as field-collected information on plant traits—are pooled and analysed to map the functional diversity of tropical forest canopies globally.

Inventory data from more than 1 million trees across African, Amazonian and Southeast Asian tropical forests suggests that, despite their high diversity, just 1,053 species, representing a consistent ~2.2% of tropical tree species in each region, constitute half of Earth’s 800 billion tropical trees.

A base-editing approach optimized to target the retina shows high editing rates in a mouse model of Stargardt disease, as well as in nonhuman primates and ex vivo human retinal explants, paving the way for potential clinical applications.

Inclusion body myositis (IBM) is a progressive inflammatory muscle disease of unknown cause, prevalent in older adults. Through spatial and single nuclear profiling, the authors identify a selective type 2 myofiber pathology in IBM, linked to genomic stress and denervation.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Anthropogenic ground-level ozone substantially reduces the productivity of tropical forests and so their carbon drawdown, according to ozone susceptibility experiments and dynamic global vegetation modelling.

Global ocean microbiome survey reveals the bacterial family ‘Candidatus Eudoremicrobiaceae’, which includes some of the most biosynthetically diverse microorganisms in the ocean environment.

Bacterial disulfide isomerases shuffle incorrect disulfide bonds. Here, the authors structurally characterize the disulfide isomerase ScsC fromProteus mirabilisand identify a functionally important shape-shifting motif that allows ScsC to adopt a diverse range of conformations and enable swarming in the presence of copper stress.

Tumour cells with defective mitochondria are found to use glutamine-dependent reductive carboxylation, rather than oxidative metabolism, as the major pathway of citrate and lipid formation.

Unlike Amazonian forests, African forests have maintained their carbon sink until recently but by 2030 the African carbon sink will have shrunk by 14 per cent and the Amazonian sink will reach almost zero.

In this Review, the authors present a roadmap towards achieving consensus on development, analysis and interpretation of single-cell transcriptomics data in adipose tissue, including discussion of roadblocks, best practices and ideal cell-type markers for annotation of adipose tissue cell types in mice and humans.

Single-cell transcriptomics of more than 20,000 cells from two functionally distinct areas of the mouse neocortex identifies 133 transcriptomic types, and provides a foundation for understanding the diversity of cortical cell types.

Garcia-Bermudez et al. and Sullivan et al. show that endogenous aspartate is a limiting metabolite for cancer cell proliferation under hypoxia and in tumours, and that metformin depletes aspartate to limit tumour growth.

A non-canonical tricarboxylic acid cycle is required for changes in cell state.

Autotransporter proteins are localised to the bacterial surface and promote colonisation of host epithelial surfaces. Here, the authors present the crystal structure of autotransporter UpaB and show evidence for distinct binding sites for glycosaminoglycans and host fibronectin.

Oxygen in shallow shelf waters rose linearly with atmospheric oxygen in the Neoproterozoic era, potentially driving the first radiation of marine animals, but widespread ocean oxygenation came later, according to reconstructions of oxygen levels and marine productivity.

Production of oxidized biomass is necessary to support cancer cell proliferation. In this work, Li et al. provide a quantitative analysis of the cellular needs and biochemical bottlenecks in lipid biosynthesis arising from the requirement to regenerate the cofactor NAD⁺.

Crist et al. show that tumour cells disseminate and accumulate in skeletal muscle but fail to proliferate and grow due to oxidative stress, thereby explaining why skeletal muscle is resistant to metastatic colonization and outgrowth.

An international team of researchers finds high potential for improving climate projections by a more comprehensive treatment of largely ignored Arctic vegetation types, underscoring the importance of Arctic energy exchange measuring stations.

Mitochondria maintain a balance between thermogenesis and ATP synthesis, but how this is coordinated is largely unknown. Here, the authors show that MFSD7C coordinates ATP synthesis and thermogenesis in response to heme by directly binding to electron transport chain complexes and SERCA2b.

Emerging variants of SARS-CoV-2 raise concerns about vaccine efficiency. Here, the authors present a post-hoc analysis for the ChAdOx1 nCoV-19 (AZD1222) vaccine trial in Brazil and provide efficacy against symptomatic COVID-19 caused by the Zeta (P.2) and other variants.

An integrated analysis of de novo and inherited coding variants in 42,607 individuals with autism spectrum disorder identifies 60 risk genes of which five have not previously been associated with neurodevelopmental disorders.

A quantitative high-throughput screen identified an inhibitor of phosphoglycerate dehydrogenase (PHGDH), a key enzyme for serine synthesis. This inhibitor limits one-carbon unit availability for nucleotide synthesis.

Using genome-resolved metagenomics for 41 Arctic seawater samples, this ecogenomic analysis of 530 metagenome-assembled genomes (MAGs) from the polar Arctic Ocean reveals uncultured Arctic bacterial and archaeal MAGs, their gene expression patterns, habitat preferences and metabolic potential.

A potent inhibitor of the conditionally essential mitochondrial phosphate carrier protein Mir1 in the fungi Candida albicans diminishes mitochondrial oxygen consumption and causes dramatic changes in concentrations of citrate and succinate.

The genome of the wild grass Brachypodium distachyon (Brachypodium), a member of the Pooideae subfamily, is sequenced. The Pooideae are one of three subfamilies of grasses that provide the bulk of human nutrition and may become major sources of renewable energy. Availability of the genome sequence should help establish Brachypodium as a model for developing new energy and food crops.

As phase 1 of the Earth Microbiome Project, analysis of 16S ribosomal RNA sequences from more than 27,000 environmental samples delivers a global picture of the basic structure and drivers of microbial distribution.

Plastics are invaluable materials for modern society, although they result in the generation of large amounts of litter at the end of their life cycle. This Review explores the challenges and opportunities associated with the catalytic transformation of waste plastics, looking at both chemical and biological approaches to transforming such spent materials into a resource.

The Impact of Genomic Variation on Function Consortium is combining single-cell mapping, genomic perturbations and predictive modelling to investigate relationships between human genomic variation, genome function and phenotypes and will provide an open resource to the community.

Extracellular vesicles (EVs) are a class of secreted membrane particles capable of transferring biological molecules between cells. Metabolomics measurements indicate that isolated EVs also have autonomous metabolic enzyme activities, including the unexpected identification of endogenous human asparaginase activity.

Altered cancer cell metabolism can result in intracellular metabolite concentration changes. This Review discusses the mechanisms that lead to metabolite concentration changes in cancer cells, the consequences of these changes and how they might be exploited to improve cancer therapy.

The Tobacco and Genetics Consortium report meta-analyses of several smoking phenotypes across 16 cohorts including 74,053 individuals. They identify three loci associated with cigarettes smoked per day.

Silvia Acinas et al. report the Malaspina Gene Database, a gene catalogue from deep ocean microbes and the Malaspina Deep Metagenome-Assembled Genomes (MAGs) which is made publicly available. The analysis of the metabolic pathways within these MAGs sheds light on the composition and of the strategies these microbes use to survive the deep ocean microbiome.