1Infectious diseases of domesticated animals impact human well-being via food insecurity, loss of 2 livelihoods, and human infections. While much research has focused on parasites that infect single 3 host species, most parasites of domesticated mammals infect multiple species. The impact of multi-4 host parasites varies across hosts; some rarely result in death, whereas others are nearly always fatal. 5 Despite their high ecological and societal costs, we currently lack theory for predicting the lethality 6 of multi-host parasites. Here, using a global dataset of over 4000 case-fatality rates for 65 infectious 7 diseases (caused by micro and macro-parasites) and 12 domesticated host species, we show that the 8 average evolutionary distance from an infected host to other mammal host species is a strong predictor 9 of disease-induced mortality. We find that as parasites infect species outside of their documented phy-10 logenetic host range, they are more likely to result in lethal infections, with the odds of death doubling 11 for each additional 10 million years of evolutionary distance. Our results for domesticated animal 12 diseases reveal patterns in the evolution of highly lethal parasites that are difficult to observe in the 13 wild, and further suggest that the severity of infectious diseases may be predicted from evolutionary 14 relationships among hosts. 15 19 rity, labour and livelihoods, costs of prevention and control programs, and increased human infection 20 (Dehove et al., 2012). However, the severity of disease can vary dramatically among parasites. Ca-21 nine rabies alone results in approximately 59,000 human deaths and 8.6 billion USD in economic 22 losses annually (Hampson et al., 2015). By contrast, other diseases rarely result in death. For exam-23 ple, bovine brucellosis largely impacts cattle by causing abortion, infertility and reduced growth, but 24 disease induced mortality in adult cows is uncommon (McDermott et al., 2013).
25Well established theory on single-host parasites predicts that the reduction in host fitness due to 26 2 infection (termed "virulence") should evolve to an optimal level determined by a trade-off with trans-27 mission (Cressler et al., 2016). For multi-host parasites, optimal virulence may be subject to additional 28 trade-offs, with selection for high or low virulence depending on the ecologies and evolutionary his-29 tories of each susceptible host species (Woolhouse et al., 2001; Gandon, 2004; Rigaud et al., 2010).
30In the absence of trade-offs, a wider host breadth should provide a larger pool of susceptible individ-31 uals, increasing opportunities for transmission and the evolution of higher virulence (Barrett et al., 32 2009). However, adaptation to novel hosts may reduce a parasite's ability to utilize resources of their 33 co-evolved hosts (Ebert, 1998; Longdon et al., 2014), resulting in limited replication and decreased 34 virulence (Antonovics et al., 2013). This trade-off is supported by comparative studies of plant RNA 35viruses and avian malaria p...