Immunological adaptations in bats to moderate the effect of coronavirus infection
Professor of Conservation Biology
I’m interested in how biology and the environment shape biodiversity in time and space.
- Regrowing the brain; evolution and mechanisms of seasonal reversible size changes in a mammal
- Genomics of exceptions to scaling of longevity to body size
- Discovering genomic and developmental mechanisms that underlie sensory innovations critical to adaptive diversification
- Global Union of Bat Diversity Networks (GBatNet)
- Bat goblet cells as immuno-hotspots for infection of coronavirus
High viral tolerance coupled with an extraordinary regulation of the immune response makes bats a great model to study host-pathogen evolution. Although many immune-related gene gains and losses have been previously reported in bats, important gene families such as antimicrobial peptides (AMPs) remain understudied. We built an exhaustive bioinformatic pipeline targeting the major gene families of defensins and cathelicidins to explore AMP diversity and analyze their evolution and distribution across six bat families. A combination of manual and automated procedures identified 29 AMP families across queried species, with α-, β-defensins, and cathelicidins representing around 10% of AMP diversity. Gene duplications were inferred in both α-defensins, which were absent in five species, and three β-defensin gene subfamilies, but cathelicidins did not show significant shifts in gene family size and were absent in Anoura caudifer and the pteropodids. Based on lineage-specific gains and losses, we propose diet and diet-related microbiome evolution may determine the evolution of α- and β-defensins gene families and subfamilies. These results highlight the importance of building species-specific libraries for genome annotation in non-model organisms and shed light on possible drivers responsible for the rapid evolution of AMPs. By focusing on these understudied defenses, we provide a robust framework for explaining bat responses to pathogens.
Evolvability is an emergent hallmark of cancer that depends on intra-tumor heterogeneity and, ultimately, genetic variation. Mutations generated by APOBEC3 cytidine deaminases can contribute to genetic variation and the consequences of APOBEC activation differ depending on the stage of cancer, with the most significant impact observed during the early stages. However, how APOBEC activity shapes evolutionary patterns of genes in the host genome and differential impacts on cancer-associated and non-cancer genes remain unclear. Analyzing over 40,000 human protein-coding transcripts, we identified distinct distribution patterns of APOBEC3A/B TC motifs between cancer-related genes and controls, suggesting unique associations with cancer. Studying a bat species with many more APOBEC3 genes, we found diverse motif patterns in orthologs of cancer genes compared to controls, similar to humans and suggesting APOBEC evolution to reduce impacts on the genome rather than the converse. Simulations confirmed that APOBEC-induced heterogeneity enhances cancer evolution, shaping clonal dynamics through bimodal introduction of mutations in certain classes of genes. Our results suggest that a major consequence of the bimodal distribution of APOBEC affects greater cancer heterogeneity.
Bats carry viruses that can cause severe disease in other mammals. Asymptomatic infections in bats suggest 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. A systematic analysis showed that signatures of selection in immune genes are more prevalent in bats compared with other mammals. We found an excess of immune gene adaptations in the ancestral Chiroptera and many descending bat lineages, highlighting viral entry and detection factors, and regulators of antiviral and inflammatory responses. ISG15, an antiviral gene contributing to hyperinflammation during COVID-19, exhibits a deletion of a cysteine, required for homodimer formation, in rhinolophid and hipposiderid bats. Cellular infection experiments showed enhanced intracellular protein conjugation of bat ISG15 and lack of secretion into extracellular space, where human ISG15 stimulates inflammation. Our work highlights molecular mechanisms contributing to viral tolerance and disease resistance in bats.
Ariadna E. Morales, Yue Dong, Thomas Brown, Kaushal Baid, Dimitrios - Georgios Kontopoulos, Victoria Gonzalez, Zixia Huang, Alexis-Walid Ahmed, Leon Hilgers, Sylke Winkler, Graham M. Hughes, Xiaomeng Li, Bogdan M. Kirilenko, Paolo Devanna, Tanya M. Lama, Yomiran Nissan, Martin Pippel, Liliana M. Dávalos, Sonja C. Vernes, Sebastien J. Puechmaille, Stephen J. Rossiter, Yossi Yovel, Joseph B. Prescott, Andreas Kurth, David A. Ray, Burton K. Lim, Eugene Myers, Emma C. Teeling, Arinjay Banerjee, Aaron T. Irving, Michael Hiller
Comprising more than 1,400 species, bats possess adaptations unique among mammals including powered flight, unexpected longevity, and …
Diana D. Moreno-Santillán, Tanya Lama, Yocelyn Gutiérrez Guerrero, Alexis Brown, Paul Donat, Huabin Zhao, Stephen Rossiter, Laurel R. Yohe, Joshua Potter, Emma C. Teeling, Sonja Vernes, Kalina T.J. Davies, Eugene Myers, Graham M. Hughes, Zixia Huang, Federico G. Hoffmann, Angelique P. Corthals, David Ray, Liliana M. Dávalos