@article {Yang2023.03.08.531760, author = {Lu Yang and Flora Borne and Matthew L. Aardema and Ying Zhen and Julie Peng and Mariana Wu and Regina Visconti and Anja Betz and Bartholomew P. Roland and Aaron D. Talsma and Mike J. Palladino and Georg Petschenka and Peter Andolfatto}, title = {The path to {\textquotedblleft}femmes fatales{\textquotedblright}: the evolution of toxin resistance in predatory fireflies}, elocation-id = {2023.03.08.531760}, year = {2023}, doi = {10.1101/2023.03.08.531760}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Toxic cardiotonic steroids (CTS) act as a defense mechanism in many firefly species (Lampyridae) by inhibiting a crucial enzyme called Na+,K+-ATPase (NKA). While most fireflies produce these toxins internally, species of the genus Photuris acquire them from a surprising source: predation on other fireflies. The contrasting physiology of toxin metabolism between Photuris and other firefly genera suggests the possibility of distinct strategies evolving to prevent self-intoxication. Our study demonstrates that both Photuris and their firefly prey have evolved highly-resistant NKAs. Using an evolutionary analysis of the specific target of CTS (ATPĪ±) in fireflies, and gene-editing in Drosophila, we find that the initial steps towards resistance were shared among Photuris and other firefly lineages. However, the Photuris lineage subsequently underwent multiple rounds of gene duplication and neofunctionalization, resulting in the development of ATPĪ± paralogs that are differentially expressed and exhibit increasing resistance to CTS. In contrast, other firefly species have maintained a single copy. Our results implicate gene duplication as a facilitator in the transition of Photuris to its distinct ecological role as predator of toxic firefly prey.One-Sentence Summary Gene duplication is associated with distinct ecological roles for predatory fireflies and their firefly prey.Competing Interest StatementThe authors have declared no competing interest.}, URL = {https://www.biorxiv.org/content/early/2023/05/23/2023.03.08.531760}, eprint = {https://www.biorxiv.org/content/early/2023/05/23/2023.03.08.531760.full.pdf}, journal = {bioRxiv} }