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1. Six reference-quality genomes reveal evolution of bat adaptations

   https://doi.org/10.1038/s41586-020-2486-3  

   Jebb, David; Huang, Zixia; Pippel, Martin; Hughes, Graham M.; Lavrichenko, Ksenia; Devanna, Paolo; Winkler, Sylke; Jermiin, Lars S.; Skirmuntt, Emilia C.; Katzourakis, Aris; et al (July 2020, Nature)
2. Bat genomes illuminate adaptations to viral tolerance and disease resistance

   https://doi.org/10.1038/s41586-024-08471-0  

   Morales, Ariadna E; Dong, Yue; Brown, Thomas; Baid, Kaushal; Kontopoulos, Dimitrios_- Georgios; Gonzalez, Victoria; Huang, Zixia; Ahmed, Alexis-Walid; Bhuinya, Arkadeb; Hilgers, Leon; et al (February 2025, Nature)

   Zoonoses are infectious diseases transmitted from animals to humans. Bats have been suggested to harbour more zoonotic viruses than any other mammalian order1. Infections in bats are largely asymptomatic2,3, 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. 

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3. Reference-quality bat genomes illuminate adaptations to viral tolerance and disease resistance

   https://doi.org/10.21203/rs.3.rs-2557682/v1  

   Morales, Ariadna; Dong, Yue; Brown, Thomas; Baid, Kaushal; Kontopoulos, Dimitrios; Gonzalez, Victoria; Huang, Zixia; Ahmed, Alexis; Hilgers, Leon; Winkler, Sylke; et al (February 2023, Research Square)

   Abstract 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. 

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4. The complete mitochondrial genomes and phylogenetic analysis of two Nycteribiidae bat flies (Diptera: Hippoboscoidea)

   https://doi.org/10.1080/23802359.2022.2107450  

   Porter, Megan L.; Lutz, Holly; Steck, Mireille; Chong, Rebecca A. (August 2022, Mitochondrial DNA Part B)
5. Comparative analysis of bat immunoglobulin constant regions identifies adaptations of bat immunity

   https://doi.org/10.1111/nyas.70048  

   Thavornwatanayong, Thongthai; Wiantoro, Sigit; Kaczmarek, Maria E; Kantorski, Matthew; Segovia, Emily; Reyes, Kanelly; Vuong, Bao Q; Tsang, Susan M (September 2025, Annals of the New York Academy of Sciences)

   Abstract Our understanding of bat immunoglobulins (Igs) and their functions remains limited despite the importance of Ig activation in both innate and adaptive immune responses. Positive selection is known to act on other immune genes needed to mount adaptive immune responses, suggesting that selection may also act on bat Ig constant regions. To test whether bat Ig constant regions have evolved adaptations related to immunity, we reconstructed the evolutionary relationships of the constant region of bat IgM, IgA, and IgG genes and analyzed their sequences for signs of selection. Our phylogenies yielded topologies that generally agreed with known evolutionary relationships between bat families and indicated that some branches preceding large species radiation underwent positive selection. At the amino acid level, we found positive selection near sites where IgM and IgG constant regions interact with the C1q complex. Positive signals also clustered around sites where IgM and IgA interact with Fc alpha/mu receptor (Fcα/µR) and where IgG interacts with neonatal Fc receptor (FcrRn) and tripartite motif containing 21 (TRIM21). Because Ig binding to C1q, Fcα/µR, FcrRn, and TRIM21 promotes innate and adaptive immune responses in mice and humans, our findings suggest a similar role for Igs in bat immune responses. 

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