Quantifying the strength of viral fitness tradeoffs between hosts: A meta-analysis of pleiotropic fitness effects

The range of hosts a given virus can infect is widely presumed to be limited by fitness tradeoffs between alternative hosts. These fitness tradeoffs may arise naturally due to antagonistic pleiotropy if mutations that increase fitness in one host tend to decrease fitness in alternate hosts. Yet there is also growing recognition that positive pleiotropy may be more common than previously appreciated. With positive pleiotropy, mutations have concordant fitness effects such that a beneficial mutation can simultaneously increase fitness in different hosts, providing a genetic mechanism by which selection can overcome fitness tradeoffs. How readily evolution can overcome fitness tradeoffs therefore depends on the overall distribution of mutational fitness effects between hosts, including the relative frequency of antagonistic versus positive pleiotropy. We therefore conducted a systematic meta-analysis of the pleiotropic fitness effects of viral mutations reported in different hosts. Our analysis indicates that while both antagonistic and positive pleiotropy are common, fitness effects are overall positively correlated between hosts and unconditionally beneficial mutations are not uncommon. Moreover, the relative frequency of antagonistic versus positive pleiotropy may simply reflect the underlying frequency of beneficial and deleterious mutations in individual hosts. Given a mutation is beneficial in one host, the probability that it is deleterious in another host is roughly equal to the probability that any mutation is deleterious, suggesting there is no natural tendency towards antagonistic pleiotropy. The widespread prevalence of positive pleiotropy suggests that many fitness tradeoffs may be readily overcome by evolution given the right selection pressures. Lay summary Evolutionary theory suggests that fitness tradeoffs between alternative environments constrain the potential for organisms to simultaneously adapt to multiple environments. Likewise, fitness tradeoffs between alternative hosts are widely believed to limit the ability of viruses to adapt to multiple hosts and thereby expand their host range. How strongly viruses are constrained by such tradeoffs will largely depend on the fitness effects of new mutations. Fitness tradeoffs may inevitably constrain viral evolution if mutations that increase fitness in one host tend to decrease fitness in alternative hosts. However, mutations can sometimes increase fitness in multiple hosts, allowing viruses to adapt to new hosts without paying fitness costs. Geneticists refer to these two scenarios as antagonistic and positive pleiotropy depending on whether mutations have opposite or concordant fitness effects. Because the relative frequency of antagonistic versus positive pleiotropy is centrally important to viral evolution, we conducted a systematic meta-analysis of the fitness effects of mutations reported in different hosts. Our analysis reveals that cases of positive pleiotropy where mutations have beneficial effects in more than one host may be sufficiently common for evolution to resolve many apparent fitness tradeoffs between hosts.