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There are outstanding evolutionary questions on the recent emergence of human coronavirus SARS-CoV-2 including the role of reservoir species, the role of recombination and its time of divergence from animal viruses. We find that the sarbecoviruses—the viral subgenus containing SARS-CoV and SARS-CoV-2—undergo frequent recombination and exhibit spatially structured genetic diversity on a regional scale in China. SARS-CoV-2 itself is not a recombinant of any sarbecoviruses detected to date, and its receptor-binding motif, important for specificity to human ACE2 receptors, appears to be an ancestral trait shared with bat viruses and not one acquired recently via recombination. To employ phylogenetic dating methods, recombinant regions of a 68-genome sarbecovirus alignment were removed with three independent methods. Bayesian evolutionary rate and divergence date estimates were shown to be consistent for these three approaches and for two different prior specifications of evolutionary rates based on HCoV-OC43 and MERS-CoV. Divergence dates between SARS-CoV-2 and the bat sarbecovirus reservoir were estimated as 1948 (95% highest posterior density (HPD): 1879–1999), 1969 (95% HPD: 1930–2000) and 1982 (95% HPD: 1948–2009), indicating that the lineage giving rise to SARS-CoV-2 has been circulating unnoticed in bats for decades. In this manuscript, the authors address evolutionary questions on the emergence of SARS-CoV-2. They find that SARS-CoV-2 is not a recombinant of any sarbecoviruses detected to date, and that the bat and pangolin sequences most closely related to SARS-CoV-2 probably diverged several decades ago or possibly earlier from human SARS-CoV-2 samples.

Broad paradigms of vertebrate genomic repeat element evolution have been largely shaped by analyses of mammalian and avian genomes. Here, based on analyses of genomes sequenced from over 60 squamate reptiles (lizards and snakes), we show that patterns of genomic repeat landscape evolution in squamates challenge such paradigms. Despite low variance in genome size, squamate genomes exhibit surprisingly high variation among species in abundance (ca. 25–73% of the genome) and composition of identifiable repeat elements. We also demonstrate that snake genomes have experienced microsatellite seeding by transposable elements at a scale unparalleled among eukaryotes, leading to some snake genomes containing the highest microsatellite content of any known eukaryote. Our analyses of transposable element evolution across squamates also suggest that lineage-specific variation in mechanisms of transposable element activity and silencing, rather than variation in species-specific demography, may play a dominant role in driving variation in repeat element landscapes across squamate phylogeny. Large-scale patterns of genomic repeat element evolution have been studied mainly in birds and mammals. Here, the authors analyze the genomes of over 60 squamate reptiles and show high variation in repeat elements compared to mammals and birds, and particularly high microsatellite seeding in snakes.

Background Snake venoms are trophic adaptations that represent an ideal model to examine the evolutionary factors that shape polymorphic traits under strong natural selection. Venom compositional variation is substantial within and among venomous snake species. However, the forces shaping this phenotypic complexity, as well as the potential integrated roles of biotic and abiotic factors, have received little attention. Here, we investigate geographic variation in venom composition in a wide-ranging rattlesnake ( Crotalus viridis viridis ) and contextualize this variation by investigating dietary, phylogenetic, and environmental variables that covary with venom. Results Using shotgun proteomics, venom biochemical profiling, and lethality assays, we identify 2 distinct divergent phenotypes that characterize major axes of venom variation in this species: a myotoxin-rich phenotype and a snake venom metalloprotease (SVMP)-rich phenotype. We find that dietary availability and temperature-related abiotic factors are correlated with geographic trends in venom composition. Conclusions Our findings highlight the potential for snake venoms to vary extensively within species, for this variation to be driven by biotic and abiotic factors, and for the importance of integrating biotic and abiotic variation for understanding complex trait evolution. Links between venom variation and variation in biotic and abiotic factors indicate that venom variation likely results from substantial geographic variation in selection regimes that determine the efficacy of venom phenotypes across populations and snake species. Our results highlight the cascading influence of abiotic factors on biotic factors that ultimately shape venom phenotype, providing evidence for a central role of local selection as a key driver of venom variation.

Schistosomiasis persists in Asian regions despite aggressive elimination measures. To identify factors enabling continued parasite transmission, we performed reduced representation genome sequencing on Schistosoma japonicum miracidia collected across multiple years from transmission hotspots in Sichuan, China. We discovered strong geographic structure, suggesting that local, rather than imported, reservoirs are key sources of persistent infections in the region. At the village level, parasites collected after referral for praziquantel treatment are closely related to local pre-treatment populations. Schistosomes within villages are also highly related, suggesting that only a few parasites from a limited number of hosts drive re-infection. The close familial relationships among miracidia from different human hosts also implicate short transmission routes among humans. At the individual host level, genetic evidence indicates that multiple humans retained infections following referral for treatment. Our findings suggest that end-game schistosomiasis control measures should focus on completely extirpating local parasite reservoirs and confirming successful treatment of infected human hosts.

Background Previous studies examining post-feeding organ regeneration in the Burmese python ( Python molurus bivittatus ) have identified thousands of genes that are significantly differentially regulated during this process. However, substantial gaps remain in our understanding of coherent mechanisms and specific growth pathways that underlie these rapid and extensive shifts in organ form and function. Here we addressed these gaps by comparing gene expression in the Burmese python heart, liver, kidney, and small intestine across pre- and post-feeding time points (fasted, one day post-feeding, and four days post-feeding), and by conducting detailed analyses of molecular pathways and predictions of upstream regulatory molecules across these organ systems. Results Identified enriched canonical pathways and upstream regulators indicate that while downstream transcriptional responses are fairly tissue specific, a suite of core pathways and upstream regulator molecules are shared among responsive tissues. Pathways such as mTOR signaling, PPAR/LXR/RXR signaling, and NRF2-mediated oxidative stress response are significantly differentially regulated in multiple tissues, indicative of cell growth and proliferation along with coordinated cell-protective stress responses. Upstream regulatory molecule analyses identify multiple growth factors, kinase receptors, and transmembrane receptors, both within individual organs and across separate tissues. Downstream transcription factors MYC and SREBF are induced in all tissues. Conclusions These results suggest that largely divergent patterns of post-feeding gene regulation across tissues are mediated by a core set of higher-level signaling molecules. Consistent enrichment of the NRF2-mediated oxidative stress response indicates this pathway may be particularly important in mediating cellular stress during such extreme regenerative growth.

Background Snakes exhibit extreme intestinal regeneration following months-long fasts that involves unparalleled increases in metabolism, function, and tissue growth, but the specific molecular control of this process is unknown. Understanding the mechanisms that coordinate these regenerative phenotypes provides valuable opportunities to understand critical pathways that may control vertebrate regeneration and novel perspectives on vertebrate regenerative capacities. Results Here, we integrate a comprehensive set of phenotypic, transcriptomic, proteomic, and phosphoproteomic data from boa constrictors to identify the mechanisms that orchestrate shifts in metabolism, nutrient uptake, and cellular stress to direct phases of the regenerative response. We identify specific temporal patterns of metabolic, stress response, and growth pathway activation that direct regeneration and provide evidence for multiple key central regulatory molecules kinases that integrate these signals, including major conserved pathways like mTOR signaling and the unfolded protein response. Conclusion Collectively, our results identify a novel switch-like role of stress responses in intestinal regeneration that forms a primary regulatory hub facilitating organ regeneration and could point to potential pathways to understand regenerative capacity in vertebrates.

The global community has adopted ambitious goals to eliminate schistosomiasis as a public health problem, and new tools are needed to achieve them. Mass drug administration programs, for example, have reduced the burden of schistosomiasis, but the identification of hotspots of persistent and reemergent transmission threaten progress toward elimination and underscore the need to couple treatment with interventions that reduce transmission. Recent advances in DNA sequencing technologies make whole-genome sequencing a valuable and increasingly feasible option for population-based studies of complex parasites such as schistosomes. Here, we focus on leveraging genomic data to tailor interventions to distinct social and ecological circumstances. We consider two priority questions that can be addressed by integrating epidemiological, ecological, and genomic information: (1) how often do non-human host species contribute to human schistosome infection? and (2) what is the importance of locally acquired versus imported infections in driving transmission at different stages of elimination? These questions address processes that can undermine control programs, especially those that rely heavily on treatment with praziquantel. Until recently, these questions were difficult to answer with sufficient precision to inform public health decision-making. We review the literature related to these questions and discuss how whole-genome approaches can identify the geographic and taxonomic sources of infection, and how such information can inform context-specific efforts that advance schistosomiasis control efforts and minimize the risk of reemergence.The global community has adopted ambitious goals to eliminate schistosomiasis as a public health problem, and new tools are needed to achieve them. Mass drug administration programs, for example, have reduced the burden of schistosomiasis, but the identification of hotspots of persistent and reemergent transmission threaten progress toward elimination and underscore the need to couple treatment with interventions that reduce transmission. Recent advances in DNA sequencing technologies make whole-genome sequencing a valuable and increasingly feasible option for population-based studies of complex parasites such as schistosomes. Here, we focus on leveraging genomic data to tailor interventions to distinct social and ecological circumstances. We consider two priority questions that can be addressed by integrating epidemiological, ecological, and genomic information: (1) how often do non-human host species contribute to human schistosome infection? and (2) what is the importance of locally acquired versus imported infections in driving transmission at different stages of elimination? These questions address processes that can undermine control programs, especially those that rely heavily on treatment with praziquantel. Until recently, these questions were difficult to answer with sufficient precision to inform public health decision-making. We review the literature related to these questions and discuss how whole-genome approaches can identify the geographic and taxonomic sources of infection, and how such information can inform context-specific efforts that advance schistosomiasis control efforts and minimize the risk of reemergence.

Both the metabolic theory of ecology and dynamic energy budget theory predict that climate influences body size through its effects on first-order determinants of energetics: reactive temperatures, carbon resources and oxygen availability. Although oxygen is seldom limiting in terrestrial systems, temperature and resources vary spatially. We used redundancy analyses and variation partitioning to evaluate the influence of climatic temperature, precipitation and their seasonalities on multivariate body size across the distributions of four species of the western rattlesnake group in North America ( Crotalus pyrrhus , C. scutulatus , C. oreganus and C. viridis ). Most species showed a pattern of increased body size in cooler, mesic climates and decreased body size in warmer, xeric climates. Exceptions to the pattern provided additional context through climatic idiosyncrasies in the distributions of each species. For example, the general pattern of a negative influence of temperature on body size was not apparent for C. oreganus , which ranges across the mildest climates overall among the four species. In contrast to previous studies, we found that seasonality had negligible effects on body size. We suggest that precipitation gradients correlate positively with resource availability in driving intraspecific body size and that temperature compounds this gradient by increasing baseline metabolic demands and restricting activity in particularly warm or otherwise extreme climates.

Genomic approaches hold great promise for resolving unanswered questions about transmission patterns and responses to control efforts for schistosomiasis and other neglected tropical diseases. However, the cost of generating genomic data and the challenges associated with obtaining sufficient DNA from individual schistosome larvae (miracidia) from mammalian hosts have limited the application of genomic data for studying schistosomes and other complex macroparasites. Here, we demonstrate the feasibility of utilizing whole genome amplification and sequencing (WGS) to analyze individual archival miracidia. As an example, we sequenced whole genomes of 22 miracidia from 11 human hosts representing two villages in rural Sichuan, China, and used these data to evaluate patterns of relatedness and genetic diversity. We also down-sampled our dataset to test how lower coverage sequencing could increase the cost effectiveness of WGS while maintaining power to accurately infer relatedness. Collectively, our results illustrate that population-level WGS datasets are attainable for individual miracidia and represent a powerful tool for ultimately providing insight into overall genetic diversity, parasite relatedness, and transmission patterns for better design and evaluation of disease control efforts.

Objectives Complex physiological adaptations often involve the coordination of molecular responses across multiple tissues. Establishing transcriptomic resources for non-traditional model organisms with phenotypes of interest can provide a foundation for understanding the genomic basis of these phenotypes, and the degree to which these resemble, or contrast, those of traditional model organisms. Here, we present a one-of-a-kind gene expression dataset generated from multiple tissues of two hibernating brown bears ( Ursus arctos ). Data description This dataset is comprised of 26 samples collected from 13 tissues of two hibernating brown bears. These samples were collected opportunistically and are typically not possible to attain, resulting in a highly unique and valuable gene expression dataset. In combination with previously published datasets, this new transcriptomic resource will facilitate detailed investigation of hibernation physiology in bears, and the potential to translate aspects of this biology to treat human disease.