Extensive longevity and DNA virus-driven adaptation in nearctic Myotis bats

The genus Myotis is one of the largest clades of bats, and exhibits some of the most extreme variation in lifespans among mammals alongside unique adaptations to viral tolerance and immune defense. To study the evolution of longevity-associated traits and infectious disease, we generated near-complete genome assemblies and cell lines for 8 closely related species of Myotis. Using genome-wide screens of positive selection, analyses of structural variation, and functional experiments in primary cell lines, we identify new patterns of adaptation contributing to longevity, cancer resistance, and viral interactions in bats. We find that Myotis bats have some of the most significant variation in cancer risk across mammals and demonstrate a unique DNA damage response in primary cells of the long-lived M. lucifugus. We also find evidence of abundant adaptation in response to DNA viruses - but not RNA viruses - in Myotis and other bats in sharp contrast with other mammals, potentially contributing to the role of bats as reservoirs of zoonoses. Together, our results demonstrate how genomics and primary cells derived from diverse taxa uncover the molecular bases of extreme adaptations in non-model organisms.

Website

All analyses in the R_workflowr folder that are compiled and pushed here are automatically posted to https://myotisgenomeanalysis.netlify.app/. For more info on this, see the workflowr documentation or talk to Manny.

Collaborators

• Juan M Vazquez^1,18 - docmanny
• M Elise Lauterbur - lauterbur
• Saba Mottaghinia⁴
• Melanie Bucci²
• Devaughn Fraser^5,6
• Genavieve Gray-Sandoval²
• Léa Gaucherand⁷
• Zeinab R Haidar^8,9
• Melissa Han¹⁰
• William Kohler¹⁰
• Tanya M. Lama¹¹
• Amandine Le Corf⁴
• Clara Loyer⁴
• Sarah Maesen⁴
• Dakota McMillan^1,12
• Stacy Li^1,13
• Johnathan Lo¹³
• Carine Rey⁴
• Samantha LR Cape^l6
• Michael Singer¹⁴
• Kathleen Slocum¹⁵
• William Thomas¹⁶
• Janet Debelak Tyburec¹⁷
• Sarah Villa¹⁴
• Richard Miller¹⁰
• Michael Buchalski⁵
• Jose Pablo Vazquez-Medina¹
• Sébastien Pfeffer⁷
• Lucie Etienne^4,19*
• David Enard^2,19,20** - davidpierreenard
• Peter H Sudmant^{1,13,19,20,21***} - petersudmant - Lab Website

Affiliations:

1. Department of Integrative Biology, University of California, Berkeley, Berkeley, CA USA
2. Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ USA
3. Current affiliation: Department of Biology, University of Vermont, Burlington, VT USA
4. Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, UCBL1, CNRS UMR5308, Ecole Normale Supérieure ENS de Lyon, Université de Lyon, Lyon, France
5. Wildlife Genetics Research Unit, Wildlife Health Laboratory, California Department of Fish and Wildlife, Sacramento, CA, United States
6. Current affiliation: Wildlife Diversity Program, Wildlife Division, Connecticut Department of Energy and Environmental Protection, Burlington, CT, United States
7. Université de Strasbourg, Architecture et Réactivité de l'ARN, Institut de Biologie Moléculaire et Cellulaire du CNRS, Strasbourg, France.
8. Department of Biology, California State Polytechnic University, Humboldt, Arcata, CA USA
9. Current affiliation: Western EcoSystems Technology Inc, Cheyenne, WY USA
10. Department of Pathology and Clinical Laboratories, University of Michigan, Ann Arbor, MI USA
11. Department of Biological Sciences, Smith College, Northampton, MA USA
12. Department of Science and Biotechnology, Berkeley City College, Berkeley, CA USA
13. Center for Computational Biology, University of California, Berkeley, Berkeley, CA USA
14. Department of Molecular and Cellular Biology, University of California, Berkeley, Berkeley, CA USA
15. Bat Conservation International, Austin, TX USA
16. Department of Ecology and Evolution, Stony Brook University, Stony Brook NY USA
17. Bat Survey Solutions, LLC, Tucson, AZ USA
18. These authors contributed equally
19. Senior author
20. These authors contributed equally
21. Lead contact

* Correspondence: lucie.etienne@ens-lyon.fr

** Correspondence: denard@arizona.edu

*** Correspondence: psudmant@berkeley.edu

Repo Structure:

• assembly/: Contains the scripts, Snakefiles, and other parts necessary for assembling all genomes
• analyses/: Contains codefor analyses done in the paper in their own folders.
• data/: Serves as a central spot to place files and outputs that are dependencies for other projects.
• manuscript/: Holds the final elementsfor the paper.