Biology subjects

Simmons, N. B.

Publications and source records attributed to Simmons, N. B..

25 records · Page 2Linked to original sources

bioRxiv2020

Body size affects immune cell proportions in birds and non-volant mammals, but not bats

Powered flight has evolved several times in vertebrates and constrains morphology and physiology in ways that likely have shaped how organisms cope with infections. Some of these constraints likely have impacts on aspects of immunology, such that larger fliers might prioritize risk reduction and safety. Addressing how the evolution of flight may have driven relationships between body size and immunity could be particularly informative for understanding the propensity of some taxa to harbor many virulent and sometimes zoonotic pathogens without showing clinical disease. Here, we used a scaling framework to quantify scaling relationships between body mass and the proportions of two types of white blood cells--lymphocytes, and granulocytes (neutr-/heterophils)--across 60 bat species, 414 bird species, and 256 non-volant mammal species. By using phylogenetically-informed statistical models on field-collected data from wild Neotropical bats, data gleaned from other wild bats available in the literature, and data from captive non-volant mammals and birds, we show that lymphocyte and neutrophil proportions do not vary systematically with body mass among bats. In contrast, larger birds and non-volant mammals have disproportionately higher granulocyte proportions than expected for their body size. Future comparative studies of wild bats, birds, and non-volant mammals of similar body mass should aim to further differentiate evolutionary effects and other aspects of life history on immune defense. Summary statementPowered flight might constrain morphology such that certain immunological features are prioritized. We show that bats largely have similar cell proportions across body mass compared to strong allometric scaling relationships in birds and non-flying mammals.

physiology↗

bioRxiv2020

Surveying the vampire bat (Desmodus rotundus) serum proteome: a resource for identifying immunological proteins and detecting pathogens

Bats are increasingly studied as model systems for longevity and as natural hosts for some virulent viruses. Yet our ability to characterize immune mechanisms of viral tolerance and to quantify infection dynamics in wild bats is often limited by small sample volumes and few species-specific reagents. Here, we demonstrate how proteomics can overcome these limitations by using data-independent acquisition-based shotgun proteomics to survey the serum proteome of 17 vampire bats (Desmodus rotundus) from Belize. Using just 2 L of sample and relatively short separations of undepleted serum digests, we identified 361 proteins across five orders of magnitude. Data are available via ProteomeXchange with identifier PXD022885. Levels of immunological proteins in vampire bat serum were then compared to human plasma via published databases. Of particular interest were anti-viral and anti-bacterial components, circulating 20S proteasome complex, and proteins involved in redox activity; whether any results are specific to vampire bats could be assessed by future pan-mammalian analyses. Lastly, we used known virus proteomes to identify Rh186 from Macacine herpesvirus 3 and ORF1a from Middle East respiratory syndrome-related coronavirus, indicating that mass spectrometry-based techniques show promise for pathogen detection. Overall, these results can be used to design targeted mass-spectrometry assays to quantify immunological markers and detect pathogens. More broadly, our findings also highlight the application of proteomics in advancing wildlife immunology and pathogen surveillance.

molecular biology↗

bioRxiv2020

Unraveling molecular mechanisms of immunity and cancer-resistance using the genomes of the Neotropical bats Artibeus jamaicensis and Pteronotus mesoamericanus

Bats are exceptional among mammals for their powered flight, extended lifespans, and robust immune systems. To investigate the genomic underpinnings of unique bat adaptations, we sequenced the genomes of the Jamaican fruit bat (Artibeus jamaicensis) and the Mesoamerican mustached bat (Pteronotus mesoamericanus) and compared them to a diverse collection of 13 additional bat species together with other mammals. We used the Oxford Nanopore Technologies long-read platform to generate highly complete assemblies (N50: 28-29Mb) and facilitate analysis of complex genomic regions containing duplicated genes. Using gene family size analysis, we found that the type I interferon locus was contracted by eight genes in the most recent common ancestor (MRCA) of bats, shifting the proportion of interferon-{omega} to interferon- and making interferon-{omega} the most common type I interferon in bats. Antiviral genes stimulated by type I interferons were also rapidly evolving, with interferon-induced transmembrane genes experiencing a lineage-specific duplication and strong positive selection in the gene IFIT2. Moreover, the lineage of phyllostomid bats showed an unprecedented expansion of PRDM9, a recombination-related gene also involved in infection responses, raising the possibility that this gene contributes to bat antiviral defenses. These modifications in the bat innate immune system may be important adaptations allowing them to harbor viruses asymptomatically. We additionally found evidence of positive selection on the branch leading to the MRCA of bats acting on 33 tumor suppressors and six DNA repair genes, which may contribute to the low cancer rates and longevity observed across bats. These new genomic resources enable insights into the extraordinary adaptations of bats, with implications for mammalian evolutionary studies and public health.

genomics↗

bioRxiv2020

Temporal patterns of vampire bat rabies and host connectivity in Belize

In the Neotropics, vampire bats (Desmodus rotundus) are the main reservoir host for rabies, a highly fatal encephalitis caused by viruses in the genus Lyssavirus. Although patterns of rabies virus exposure and infection have been well-studied for vampire bats in South America and Mexico, exploring the ecology of vampire bat rabies in other regions is crucial for predicting risks to livestock and humans. In Belize, rabies outbreaks in livestock have increased in recent years, underscoring the need for systematic data on viral dynamics in vampire bats. In this study, we examine the first three years of a longitudinal study on the ecology of vampire bat rabies in northern Belize. Rabies seroprevalence in bats was high across years (29-80%), suggesting active and endemic virus circulation. Across two locations, the seroprevalence time series per site were inversely related and out of phase by at least a year. Microsatellite data demonstrated historic panmixia of vampire bats, and mark-recapture detected rare but contemporary inter-site dispersal. This degree of movement could facilitate spatial spread of rabies virus but is likely insufficient to synchronize infection dynamics, which offers one explanation for the observed phase lag in seroprevalence. More broadly, our analyses suggest frequent transmission of rabies virus within and among vampire bat roosts in northern Belize and highlight the need for future spatiotemporal, phylogenetic, and ecological studies of vampire bat rabies in Central America.

ecology↗

bioRxiv2020

Predicting wildlife hosts of betacoronaviruses for SARS-CoV-2 sampling prioritization

Despite global investment in One Health disease surveillance, it remains difficult--and often very costly--to identify and monitor the wildlife reservoirs of novel zoonotic viruses. Statistical models can be used to guide sampling prioritization, but predictions from any given model may be highly uncertain; moreover, systematic model validation is rare, and the drivers of model performance are consequently under-documented. Here, we use bat hosts of betacoronaviruses as a case study for the data-driven process of comparing and validating predictive models of likely reservoir hosts. In the first quarter of 2020, we generated an ensemble of eight statistical models that predict host-virus associations and developed priority sampling recommendations for potential bat reservoirs and potential bridge hosts for SARS-CoV-2. Over more than a year, we tracked the discovery of 40 new bat hosts of betacoronaviruses, validated initial predictions, and dynamically updated our analytic pipeline. We find that ecological trait-based models perform extremely well at predicting these novel hosts, whereas network methods consistently perform roughly as well or worse than expected at random. These findings illustrate the importance of ensembling as a buffer against variation in model quality and highlight the value of including host ecology in predictive models. Our revised models show improved performance and predict over 400 bat species globally that could be undetected hosts of betacoronaviruses. Although 20 species of horseshoe bats (Rhinolophus spp.) are known to be the primary reservoir of SARS-like viruses, we find at least three-fourths of plausible betacoronavirus reservoirs in this bat genus might still be undetected. Our study is the first to demonstrate through systematic validation that machine learning models can help optimize wildlife sampling for undiscovered viruses and illustrates how such approaches are best implemented through a dynamic process of prediction, data collection, validation, and updating.

ecology↗

bioRxiv2019

Ecological and evolutionary drivers of hemoplasma infection and bacterial genotype sharing in a Neotropical bat community

Most emerging pathogens can infect multiple species, underscoring the importance of understanding the ecological and evolutionary factors that allow some hosts to harbor greater infection prevalence and share pathogens with other species. However, our understanding of pathogen jumps is primarily based around viruses, despite bacteria accounting for the greatest proportion of zoonoses. Because bacterial pathogens in bats (Order: Chiroptera) can have conservation and human health consequences, studies that examine the ecological and evolutionary drivers of bacterial prevalence and barriers to pathogen sharing are crucially needed. We here studied hemotropic Mycoplasma spp. (i.e., hemoplasmas) across a species-rich bat community in Belize over two years. Across 469 bats spanning 33 species, half of individuals and two-thirds of species were hemoplasma positive. Infection prevalence was higher for males and for species with larger body mass and colony sizes. Hemoplasmas displayed high genetic diversity (21 novel genotypes) and strong host specificity. Evolutionary patterns supported co-divergence of bats and bacterial genotypes alongside phylogenetically constrained host shifts. Bat species centrality to the network of shared hemoplasma genotypes was phylogenetically clustered and unrelated to prevalence, further suggesting rare--but detectable--bacterial sharing between species. Our study highlights the importance of using fine phylogenetic scales when assessing host specificity and suggests phylogenetic similarity may play a key role in host shifts for not only viruses but also bacteria. Such work more broadly contributes to increasing efforts to understand cross-species transmission and epidemiological consequences of bacterial pathogens.

ecology↗

bioRxiv2019

Targeted sequence capture outperforms RNA-Seq and degenerate-primer PCR cloning for sequencing the largest mammalian multi-gene family

Multigene families evolve from single-copy ancestral genes via duplication, and typically encode proteins critical to key biological processes. Molecular analyses of these gene families require high-confidence sequences, but the high sequence similarity of the members can create challenges for both sequencing and downstream analyses. Focusing on the common vampire bat, Desmodus rotundus, we evaluated how different sequencing approaches performed in recovering the largest mammalian protein-coding multigene family: olfactory receptors (OR). Using the common vampire bat genome as a reference, we determined the proportion of putatively protein-coding receptors recovered by: 1) amplicons from degenerate primers sequenced via Sanger technology, 2) RNA-Seq of the main olfactory epithelium, and 3) those genes \"captured\" with probes designed from transcriptomes of closely-related species. Our initial re-annotation of the high-quality vampire bat genome resulted in >400 intact OR genes, more than double the number based on original estimates. Sanger-sequenced amplicons performed the poorest among the three approaches, detecting <33% of receptors in the genome. In contrast, the transcriptome reliably recovered >50% of the annotated genomic ORs, and targeted sequence capture recovered nearly 75% of annotated genes. Each sequencing approach assembled high-quality sequences, even if it did not recover all putative receptors in the genome. Therefore, variation among assemblies was caused by low coverage of some receptors, rather than high rates of assembly error. Given this variability, we caution against using the counts of number of intact receptors per species to model the birth-death process of multigene families. Instead, our results support the use of orthologous sequences to explore and model the evolutionary processes shaping these genes.

genomics↗