Publications

Bats are extraordinary among mammals, having uniquely evolved powered flight and laryngeal echolocation, along with disease resistance, extended healthspans and the ability to hibernate1. However, the evolutionary history of bats and the understanding of these adaptations remain unresolved. We analysed chromosome-level, long-read genome assemblies from 103 bat species, including 42 new assemblies, representing all 21 bat families. This dataset, expanded in scope and assembly quality, yielded a new bat phylogeny. We placed Myzopodidae as the earliest branch within Vespertilionoidea, and resolved yangochiropteran relationships, identifying Emballonuroidea and Vespertilionoidea as sister groups. Our analysis revealed a mosaic evolutionary history across bats and explained why previous phylogenetic studies were misled. Chromosomal ancestral-state reconstructions supported 26 ancestral bat chromosomes. We integrated a morphological dataset of 699 characters for 65 species, including 44 pre-Quaternary fossils and representatives of most living bat families, with neutrally evolving genomic sites. Fossilized birth–death and dispersal–extinction cladogenesis analyses showed that bats, and thus powered flight, probably originated in Europe in the late Palaeocene, refuting African and North American origins. Placement of the fossil †Vielasia in the oldest ‘Eochiroptera’ clade indicates that laryngeal echolocation predates crown-bat diversification. Total evidence dating, including the fossil taxa, significantly reduced unrepresented basal branch lengths compared with molecular-only divergence estimates. By integrating comprehensive genomic and morphological datasets, analysed using innovative methods, we resolve long-standing controversies in bat biology and provide new insights into the evolutionary history and trait diversification of bats.

Understanding the molecular basis of neurodegeneration requires a comprehensive map of the genome’s protein-coding output. Although thousands of small open reading frames (ORFs) are translated in the human brain, proteomic evidence for their encoded microproteins (MPs) (≤150 amino acids (aa)) remains limited. Here, we present a brain MP atlas that integrates transcriptomics, mass spectrometry and deep-learning-predicted spectra across more than 600 postmortem frontal cortex samples with and without Alzheimer’s disease (AD). We identified 1,067 MPs absent from reviewed UniProtKB entries with high-confidence spectral support. A subset is differentially expressed in AD independently of the annotated main ORF at the same locus. A small ORF expressed by MKKS encodes a 63-amino-acid MP that is the locus’s predominant translation product and is downregulated in AD; its loss impairs microglial mitochondrial respiration, implicating it in microglial bioenergetics. This atlas expands the annotated brain proteome and provides a resource for studying MPs in aging and neurodegeneration.

Nuclear receptors are key effectors of metabolic programs; however, the contribution of co-regulatory complexes in maintaining metabolic homeostasis is not fully understood. Here, we show that modulation of the constitutive androstane receptor (CAR) by the co-repressor silencing mediator of retinoic acid and thyroid hormone receptors (SMRT) is required for bile acid (BA) homeostasis. Transcriptional changes in the livers of mice harboring a targeted disruption in one of the nuclear receptor-interacting domains (RIDs), SMRTmRID1 mice, revealed increased expression of CAR target genes involved in BA export. Consistent with this, SMRTmRID1 mice challenged with a high-fat diet showed increased BAs in serum and urine with commensurate decreases in the liver and intestines. Notably, the reduction in intestinal BAs led to decreased activity of the BA receptor farnesoid X receptor (FXR). This reduction in FXR activity compromised the integrity of the intestinal barrier, increased bacterial burden, and augmented intestinal inflammation. Moreover, SMRTmRID1 mice were susceptible to intestinal damage, with higher mortality rates in acute colitis and colitis-associated cancer models. Treatment with a synthetic FXR agonist (XL335) rescued SMRTmRID1 mice during acute colitis. Collectively, these studies highlight the importance of SMRT in maintaining BA homeostasis through direct and indirect regulation of hepatic CAR and intestinal FXR activity, respectively, and point to potential therapeutic routes for combating intestinal pathologies associated with a high-fat diet.

The DNA damage response (DDR) is a sophisticated network of cellular pathways whose perturbation leads to genome instability and is a key hallmark of oncogenesis. Here, we present data from 32 genome-scale loss-of-function CRISPR interference chemical–genetic screens with inhibitors targeting core constituents of the DDR machinery (PARP, ATR, ATM, DNAPK and WEE1), as both single agents and in combination with poly(ADP-ribose) polymerase inhibitors. These experiments identify >1,000 genes whose perturbation modifies the DDR and provides a rich resource to the DDR community. In addition, this compendium of functional genomics data reveals key principles governing the DDR and highlights a strong chemical–genetic interaction between loss of activity of the peroxiredoxin PRDX1 and all tested DDR inhibitors through a mechanism involving iron availability mediated by an MRGBP–PAX7–IREB2 axis. Our data position PRDX1 as a key suppressor of DNA damage accumulation and potential druggable target in combination with DDR inhibitors. (Figure presented.)

The search for life beyond Earth has focused on planets and moons with liquid water, reflecting the assumption that complex biomolecules require aqueous environments to remain stable and functional. Such a view excludes a wide class of planetary settings, including the concentrated sulfuric acid clouds of Venus, where extreme acidity and minimal water are thought to preclude molecular structure despite suitable temperatures. A growing body of evidence shows that a wide range of organic molecules can remain stable in concentrated sulfuric acid, including nucleic acid bases, amino acids, lipid micelles and vesicles, and peptide nucleic acid (PNA), but such stability does not address whether macromolecules can retain folded structures required for function. Using NMR spectroscopy, here we show that three peptides adopt stable, well-defined folded structures in concentrated (98% w/w) sulfuric acid, an extreme solvent environment that has been long assumed to be incompatible with biomolecules. The peptides form compact Ω-loop conformations stabilized by solvent-mediated interactions and intramolecular hydrogen bonding. This finding strongly counters conventional thinking where sulfuric acid would destroy peptide bonds via acid-catalyzed hydrolysis. Here, the near absence of water in 98% (w/w) sulfuric acid means hydrolysis does not occur. The result identifies a regime in which macromolecular structure persists under conditions long considered incompatible with life. The finding expands the range of planetary environments that may support complex chemistry and motivates renewed consideration of chemically diverse exoplanets in the search for signs of life beyond Earth.

Field-based monitoring of tree species in forests is often sparse due to logistical constraints. Remote sensing enables repeated, spatially contiguous collection of reflectance data across large areas. Tree species classification accuracy using such data is variable, likely because most studies use observational datasets where species occurrence correlates with environmental variation. We used two sites of a tree biodiversity experiment in Germany (BIOTREE: Kaltenborn and Bechstedt), where different species have been planted with high replication under controlled diversity levels, to assess how well tree species could be classified using reflectance data from airborne imaging spectroscopy and different classification methods (linear discriminant analysis, LDA, and a non-linear support vector machine, SVM). Reflectance data for 589 wavelengths between 400–2400 nm were acquired at 1 m spatial resolution during peak growing season. Reflectance spectra showed large and significant variation between taxonomic classes, orders, and species, and weak, but still significant, interactions between classes or orders and diversity levels. Classification accuracy reached 100% in training datasets, 77%–83% for the four species in Kaltenborn prediction datasets, and 31%–49% for the 16 species in Bechstedt prediction datasets. LDA provided more accurate predictions than SVM, and using similarly-spaced original wavelengths with LDA was as efficient as using principal components derived from the original data. While airborne imaging spectroscopy effectively distinguished up to four tree species in our datasets, classification accuracy was lower when 16 species had to be distinguished. In these cases, the methodology may be more useful for functional diversity monitoring than for tree species classification.

Emerging evidence shows that responses to deforestation can differ both across species and among populations of the same species. The reasons underlying these complex patterns are unclear, and this lack of clarity is a barrier to accurate monitoring and prediction of biodiversity change. Using data from 2,262 bird species across 7,326 sites from all forested continents, we show that between-species and within-species variations in responses to forest cover are mediated by temperature. Populations in warmer macroclimates tend to decline in incidence in deforested landscapes because hotter microclimates push them closer to their species’ realized upper thermal tolerance limits. By contrast, populations in cooler macroclimates tend to be less affected by or even benefit from deforestation, as microclimatic temperatures are pushed closer to more optimal temperatures. Our findings offer an empirically grounded framework for biodiversity models that move beyond fixed species responses and incorporate interactions between temperature and land-use change.

Fucoidans, a class of complex polysaccharides produced by brown algae and diatoms, contribute to long-term carbon sequestration owing to their resistance to microbial degradation1,2. Although individual microorganisms can break down portions of these polysaccharides3, 4–5, it remains unclear whether complete breakdown is possible in nature and, if so, by what mechanisms. Here we show that fucoidans are degraded through synergistic interactions between specialized bacteria with complementary metabolic functions. Using metabolomic analysis of a reconstructed marine consortium, we uncovered metabolic guilds of bacteria that preferentially degrade either the sulfated fucose backbone or the side branches of rare monomers. This functional division of labour leads to an unexpectedly high number of synergistic interactions between different degraders that enhanced degradation efficiency up to 97.1%. Despite varying fucoidan structures across different types of algae6, the metabolic functions of degraders remained conserved, enabling quantitative prediction of degradation outcomes based on community and substrate composition. The frequent co-occurrence of functionally complementary fucoidan degraders in ocean metagenomes suggests that synergistic degradation is a globally relevant strategy. Our findings suggest that the environmental turnover of complex biopolymers depends not only on individual metabolic capabilities of degraders but also on ecological interactions shaped by substrate architecture. This work provides a mechanistic framework for understanding carbon cycling in the ocean and for engineering synthetic microbial consortia to degrade recalcitrant polysaccharides.