Ancient chicken remains reveal the origins of virulence in Marek’s disease virus

Steven R Fiddaman, Evangelos A Dimopoulos, Ophélie Lebrasseur, Louis du Plessis, Bram Vrancken, Sophy Charlton, Ashleigh F Haruda, Kristina Tabbada, Patrik G Flammer, Stefan Dascalu, Nemanja Marković, Hannah Li, Gabrielle Franklin, Robert Symmons, Henriette Baron, László Daróczi-Szabó, Dilyara N Shaymuratova, Igor V Askeyev, Olivier Putelat, Maria Sana, Hossein Davoudi, Homa Fathi, Amir Saed Mucheshi, Ali Akbar Vahdati, Liangren Zhang, Alison Foster, Naomi Sykes, Gabrielle Cass Baumberg, Jelena Bulatović, Arthur O Askeyev, Oleg V Askeyev, Marjan Mashkour, Oliver G Pybus, Venugopal Nair, Greger Larson, Adrian L Smith, Laurent A F Frantz

The pronounced growth in livestock populations since the 1950s has altered the epidemiological and evolutionary trajectory of their associated pathogens. For example, Marek's disease virus (MDV), which causes lymphoid tumors in chickens, has experienced a marked increase in virulence over the past century. Today, MDV infections kill >90% of unvaccinated birds, and controlling it costs more than US$1 billion annually. By sequencing MDV genomes derived from archeological chickens, we demonstrate that it has been circulating for at least 1000 years. We functionally tested the Meq oncogene, one of 49 viral genes positively selected in modern strains, demonstrating that ancient MDV was likely incapable of driving tumor formation. Our results demonstrate the power of ancient DNA approaches to trace the molecular basis of virulence in economically relevant pathogens.