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Environmental disturbances in the Neotropics (e.g., deforestation, agriculture intensifica-tion, urbanization) contribute to an increasing risk of cross-species transmission of microorganisms and to disease outbreaks due to changing ecosystems of reservoir hosts. Although Amazonia encompasses the greatest diversity of reservoir species, the outsized viral population diversity (virome) has yet to be investigated. Here, through a metagenomic approach, we identified 10,991 viral sequences in the saliva and feces of two bat species, Desmodus rotundus (hematophagous), trapped in two different caves surrounded by primary lowland forest, and Molossus molossus (insectivorous), trapped in forest and urban habitats. These sequences are related to 51 viral families known to infect a wide range of hosts (i.e., bacteria , plants, insects and vertebrates). Most viruses detected reflected the diet of bat species, with a high proportion of plant and insect-related viral families for M. molossus and a high proportion of vertebrate-related viral families for D. rotundus, highlighting its influence in shaping the viral diversity of bats. Lastly, we reconstructed the phylogenetic relationships for five vertebrate-related viral families (Nairoviridae, Circoviridae, Retroviridae, Herpesviri-dae, Papillomaviridae). The results showed highly supported clustering with other viral sequences of the same viral family hosted by other bat species, highlighting the potential association of viral diversity with the host's diet. These findings provide significant insight into viral bat diversity in French Guiana belonging to the Amazonian biome and emphasize that habitats and the host's dietary ecology may drive the viral diversity in the bat communities investigated.

Genetic differentiations and phylogeographical patterns are controlled by the interplay between spatial isolation and gene flow. To assess the extent of gene flow across an oceanic barrier, we explored the effect of the separation of the peninsula of Baja California on the evolution of mainland and peninsular populations of the long-lived columnar cactus Stenocereus thurberi . We analyzed twelve populations throughout the OPC distribution range to assess genetic diversity and structure using chloroplast DNA sequences. Genetic diversity was higher ( H d = 0.81), and genetic structure was lower ( G ST = 0.143) in mainland populations vs peninsular populations ( H d = 0.71, G ST = 0.358 respectively). Genetic diversity was negatively associated with elevation but positively with rainfall. Two mainland and one peninsular ancestral haplotypes were reconstructed. Peninsular populations were as isolated among them as with mainland populations. Peninsular haplotypes formed a group with one mainland coastal population, and populations across the gulf shared common haplotypes giving support to regular gene flow across the Gulf. Gene flow is likely mediated by bats, the main pollinators and seed dispersers. Niche modeling suggests that during the Last Glacial Maximum (c. 130 ka), OPC populations shrank to southern locations. Currently, Stenocereus thurberi populations are expanding, and the species is under population divergence despite ongoing gene flow. Ancestral populations are located on the mainland and although vicariant peninsular populations cannot be ruled out, they are likely the result of gene flow across the seemingly formidable barrier of the Gulf of California. Still, unique haplotypes occur in the peninsula and the mainland, and peninsular populations are more structured than those on the mainland.

Bats possess extraordinary adaptations, including flight, echolocation, extreme longevity and unique immunity. High-quality genomes are crucial for understanding the molecular basis and evolution of these traits. Here we incorporated long-read sequencing and state-of-the-art scaffolding protocols 1 to generate, to our knowledge, the first reference-quality genomes of six bat species ( Rhinolophus ferrumequinum , Rousettus aegyptiacus , Phyllostomus discolor , Myotis myotis , Pipistrellus kuhlii and Molossus molossus ). We integrated gene projections from our ‘Tool to infer Orthologs from Genome Alignments’ (TOGA) software with de novo and homology gene predictions as well as short- and long-read transcriptomics to generate highly complete gene annotations. To resolve the phylogenetic position of bats within Laurasiatheria, we applied several phylogenetic methods to comprehensive sets of orthologous protein-coding and noncoding regions of the genome, and identified a basal origin for bats within Scrotifera. Our genome-wide screens revealed positive selection on hearing-related genes in the ancestral branch of bats, which is indicative of laryngeal echolocation being an ancestral trait in this clade. We found selection and loss of immunity-related genes (including pro-inflammatory NF-κB regulators) and expansions of anti-viral APOBEC3 genes, which highlights molecular mechanisms that may contribute to the exceptional immunity of bats. Genomic integrations of diverse viruses provide a genomic record of historical tolerance to viral infection in bats. Finally, we found and experimentally validated bat-specific variation in microRNAs, which may regulate bat-specific gene-expression programs. Our reference-quality bat genomes provide the resources required to uncover and validate the genomic basis of adaptations of bats, and stimulate new avenues of research that are directly relevant to human health and disease 1 . Reference-quality genomes for six bat species shed light on the phylogenetic position of Chiroptera, and provide insight into the genetic underpinnings of the unique adaptations of this clade.

Background Although bats are natural reservoirs of many pathogens, few studies have been conducted on the genetic variation and detection of selection in major histocompatibility complex (MHC) genes. These genes are critical for resistance and susceptibility to diseases, and host–pathogen interactions are major determinants of their extensive polymorphism. Here we examined spatial patterns of diversity of the expressed MHC class II DRB gene of three sympatric Neotropical bats, Carollia perspicillata and Desmodus rotundus (Phyllostomidae), and Molossus molossus (Molossidae), all of which use the same environments (e.g., forests, edge habitats, urban areas). Comparison with neutral marker (mtDNA D-loop) diversity was performed at the same time. Results Twenty-three DRB alleles were identified in 19 C. perspicillata , 30 alleles in 35 D. rotundus and 20 alleles in 28  M. molossus . The occurrence of multiple DRB loci was found for the two Phyllostomidae species. The DRB polymorphism was high in all sampling sites and different signatures of positive selection were detected depending on the environment. The patterns of DRB diversity were similar to those of neutral markers for C. perspicillata and M. molossus. In contrast, these patterns were different for D. rotundus for which a geographical structure was highlighted. A heterozygote advantage was also identified for this species. No recombination or gene conversion event was found and phylogenetic relationships showed a trans-species mode of evolution in the Phyllostomids. Conclusions This study of MHC diversity demonstrated the strength of the environment and contrasting pathogen pressures in shaping DRB diversity. Differences between positively selected sites identified in bat species highlighted the potential role of gut microbiota in shaping immune responses. Furthermore, multiple geographic origins and/or population admixtures observed in C. perspicillata and M. molossus populations acted as an additional force in shaping DRB diversity. In contrast, DRB diversity of D. rotundus was shaped by environment rather than demographic history.

Zoonoses are infectious diseases transmitted from animals to humans. Bats have been suggested to harbour more zoonotic viruses than any other mammalian order 1 . Infections in bats are largely asymptomatic 2 , 3 , indicating limited tissue-damaging inflammation and immunopathology. To investigate the genomic basis of disease resistance, the Bat1K project generated reference-quality genomes of ten bat species, including potential viral reservoirs. Here we describe a systematic analysis covering 115 mammalian genomes that revealed that signatures of selection in immune genes are more prevalent in bats than in other mammalian orders. We found an excess of immune gene adaptations in the ancestral chiropteran branch and in many descending bat lineages, highlighting viral entry and detection factors, and regulators of antiviral and inflammatory responses. ISG15 , which is an antiviral gene contributing to hyperinflammation during COVID-19 (refs. 4 , 5 ), exhibits key residue changes in rhinolophid and hipposiderid bats. Cellular infection experiments show species-specific antiviral differences and an essential role of protein conjugation in antiviral function of bat ISG15 , separate from its role in secretion and inflammation in humans. Furthermore, in contrast to humans, ISG15 in most rhinolophid and hipposiderid bats has strong anti-SARS-CoV-2 activity. Our work reveals molecular mechanisms that contribute to viral tolerance and disease resistance in bats. A systematic analysis of 115 mammalian genomes, including 10 new bat genomes, reveals prevalent positive selection in immune genes in bats and shows key adaptations in the antiviral gene ISG15 that aid disease resistance in bats, including to coronaviruses.

Background Phylogenetic comparative analyses usually rely on a single consensus phylogenetic tree in order to study evolutionary processes. However, most phylogenetic trees are incomplete with regard to species sampling, which may critically compromise analyses. Some approaches have been proposed to integrate non-molecular phylogenetic information into incomplete molecular phylogenies. An expanded tree approach consists of adding missing species to random locations within their clade. The information contained in the topology of the resulting expanded trees can be captured by the pairwise phylogenetic distance between species and stored in a matrix for further statistical analysis. Thus, the random expansion and processing of multiple phylogenetic trees can be used to estimate the phylogenetic uncertainty through a simulation procedure. Because of the computational burden required, unless this procedure is efficiently implemented, the analyses are of limited applicability. Results In this paper, we present efficient algorithms and implementations for randomly expanding and processing phylogenetic trees so that simulations involved in comparative phylogenetic analysis with uncertainty can be conducted in a reasonable time. We propose algorithms for both randomly expanding trees and calculating distance matrices. We made available the source code, which was written in the C++ language. The code may be used as a standalone program or as a shared object in the R system. The software can also be used as a web service through the link: http://purl.oclc.org/NET/sunplin/ . Conclusion We compare our implementations to similar solutions and show that significant performance gains can be obtained. Our results open up the possibility of accounting for phylogenetic uncertainty in evolutionary and ecological analyses of large datasets.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a major threat to global health. Although varied SARS-CoV-2–related coronaviruses have been isolated from bats and SARS-CoV-2 may infect bat, the structural basis for SARS-CoV-2 to utilize the human receptor counterpart bat angiotensin-converting enzyme 2 (bACE2) for virus infection remains less understood. Here, we report that the SARS-CoV-2 spike protein receptor binding domain (RBD) could bind to bACE2 from Rhinolophus macrotis (bACE2-Rm) with substantially lower affinity compared with that to the human ACE2 (hACE2), and its infectivity to host cells expressing bACE2-Rm was confirmed with pseudotyped SARS-CoV-2 virus and SARS-CoV-2 wild virus. The structure of the SARS-CoV-2 RBD with the bACE2-Rm complex was determined, revealing a binding mode similar to that of hACE2. The analysis of binding details between SARS-CoV-2 RBD and bACE2-Rm revealed that the interacting network involving Y41 and E42 of bACE2-Rm showed substantial differences with that to hACE2. Bats have extensive species diversity and the residues for RBD binding in bACE2 receptor varied substantially among different bat species. Notably, the Y41H mutant, which exists in many bats, attenuates the binding capacity of bACE2-Rm, indicating the central roles of Y41 in the interaction network. These findings would benefit our understanding of the potential infection of SARS-CoV-2 in varied species of bats.

Zoonotic influenza A viruses of avian origin can cause severe disease in individuals, or even global pandemics, and thus pose a threat to human populations. Waterfowl and shorebirds are believed to be the reservoir for all influenza A viruses, but this has recently been challenged by the identification of novel influenza A viruses in bats 1 , 2 . The major bat influenza A virus envelope glycoprotein, haemagglutinin, does not bind the canonical influenza A virus receptor, sialic acid or any other glycan 1 , 3 , 4 , despite its high sequence and structural homology with conventional haemagglutinins. This functionally uncharacterized plasticity of the bat influenza A virus haemagglutinin means the tropism and zoonotic potential of these viruses has not been fully determined. Here we show, using transcriptomic profiling of susceptible versus non-susceptible cells in combination with genome-wide CRISPR–Cas9 screening, that the major histocompatibility complex class II (MHC-II) human leukocyte antigen DR isotype (HLA-DR) is an essential entry determinant for bat influenza A viruses. Genetic ablation of the HLA-DR α-chain rendered cells resistant to infection by bat influenza A virus, whereas ectopic expression of the HLA-DR complex in non-susceptible cells conferred susceptibility. Expression of MHC-II from different bat species, pigs, mice or chickens also conferred susceptibility to infection. Notably, the infection of mice with bat influenza A virus resulted in robust virus replication in the upper respiratory tract, whereas mice deficient for MHC-II were resistant. Collectively, our data identify MHC-II as a crucial entry mediator for bat influenza A viruses in multiple species, which permits a broad vertebrate tropism. The DR isotype of the human leukocyte antigen of the MHC class II—or its homologues in bats, pigs, mice and chickens—is an essential cell entry determinant for bat influenza A viruses.

Species richness varies widely across extant clades, but the causes of this variation remain poorly understood. We investigate the role of diversification rate heterogeneity in shaping patterns of diversity across families of extant bats. To provide a robust framework for macroevolutionary inference, we assemble a time-calibrated, species-level phylogeny using a supermatrix of mitochondrial and nuclear sequence data. We analyze the phylogeny using a Bayesian method for modeling complex evolutionary dynamics. Surprisingly, we find that variation in family richness can largely be explained without invoking heterogeneous diversification dynamics. We document only a single well-supported shift in diversification dynamics across bats, occurring at the base of the subfamily Stenodermatinae. Bat diversity is phylogenetically imbalanced, but—contrary to previous hypotheses—this pattern is unexplained by any simple patterns of diversification rate heterogeneity. This discordance may indicate that diversification dynamics are more complex than can be captured using the statistical tools available for modeling data at this scale. We infer that bats as a whole are almost entirely united into one macroevolutionary cohort, with decelerating speciation through time. There is also a significant relationship between clade age and richness, suggesting that global bat diversity may still be expanding.

Bats harbor many emerging and reemerging viruses, several of which are highly pathogenic in other mammals but cause no clinical signs of disease in bats. To determine the role of interferons (IFNs) in the ability of bats to coexist with viruses, we sequenced the type I IFN locus of the Australian black flying fox, Pteropus alecto, providing what is, to our knowledge, the first gene map of the IFN region of any bat species. Our results reveal a highly contracted type I IFN family consisting of only 10 IFNs, including three functional IFN-α loci. Furthermore, the three IFN-α genes are constitutively expressed in unstimulated bat tissues and cells and their expression is unaffected by viral infection. Constitutively expressed IFN-α results in the induction of a subset of IFN-stimulated genes associated with antiviral activity and resistance to DNA damage, providing evidence for a unique IFN system that may be linked to the ability of bats to coexist with viruses.