Effect of Host Species on Topography of the Fitness Landscape for a Plant RNA Virus

Abstract

Adaptive fitness landscapes are a fundamental concept in evolutionary biology that relate the genotypes of individuals to their fitness. In the end, the evolutionary fate of evolving populations depends on the topography of the landscape, that is, the numbers of accessible mutational pathways and possible fitness peaks (i.e., adaptive solutions). For a long time, fitness landscapes were only theoretical constructions due to a lack of precise information on the mapping between genotypes and phenotypes. In recent years, however, efforts have been devoted to characterizing the properties of empirical fitness landscapes for individual proteins or for microbes adapting to artificial environments. In a previous study, we characterized the properties of the empirical fitness landscape defined by the first five mutations fixed during adaptation of tobacco etch potyvirus (TEV) to a new experimental host, Arabidopsis thaliana. Here we evaluate the topography of this landscape in the ancestral host Nicotiana tabacum. By comparing the topographies of the landscapes for the two hosts, we found that some features remained similar, such as the existence of fitness holes and the prevalence of epistasis, including cases of sign and reciprocal sign epistasis that created rugged, uncorrelated, and highly random topographies. However, we also observed significant differences in the fine-grained details between the two landscapes due to changes in the fitness and epistatic interactions of some genotypes. Our results support the idea that not only fitness tradeoffs between hosts but also topographical incongruences among fitness landscapes in alternative hosts may contribute to virus specialization. IMPORTANCEDespite its importance for understanding virus evolutionary dynamics, very little is known about the topography of virus adaptive fitness landscapes, and even less is known about the effects that different host species and environmental conditions may have on this topography. To bridge this gap, we evaluated the topography of a small fitness landscape formed by all genotypes that result from every possible combination of the first five mutations fixed during adaptation of TEV to the novel host A. thaliana. To assess the effect that host species may have on this topography, we evaluated the fitness of every genotype in both the ancestral and novel hosts. We found that both landscapes share some macroscopic properties, such as the existence of holes and being highly rugged and uncorrelated, yet they differ in microscopic details due to changes in the magnitude and sign of fitness and epistatic effects. T he effects of mutations can be influenced by their interactions with other mutations, with the environment, or both. Epistatic interactions among genetic loci determine the ruggedness of fitness landscapes. In the absence of epistasis, landscapes are single peaked and smooth (1). For such simple landscapes, predicting the result of evolution is an easy task. In contrast, epistatic interactions create curvature in the lands...

Environment changes epistasis to alter trade‐offs along alternative evolutionary paths

“…Although specific mutation interactions changed across environments, in most environments there was a general pattern of diminishing returns epistasis. Several other studies have also found pervasive environment dependent epistasis (Caudle et al 2014;Cervera et al 2016;Remold and Lenski 2004;Flynn et al 2013;Li and Zhang 2018). Our results extend this work by describing characteristics of complete fitness landscapes across selective and alternative environments, and examining both global and local mutation interaction effects.…”

“…One consequence is that fitness trade-offs can be inconsistent, even when considering the effects of a single mutation (Remold 2012). A study of fitness of Tobacco etch potyvirus strains measured across two hosts found that genotypes engineered to contain mutations selected during evolution on one host could either increase or decrease fitness on the original host, and these differences were, at least in part, due to environment dependent epistatic interactions (Cervera et al 2016). The same kind of con-text dependence was seen when comparing cross-resistance of Plasmodium falciparum to two antimalarial drugs .…”

“…Studies that have determined the effect of environmental changes on mutation interactions have typically found interactions to be environment dependent, both when random mutations were considered or when mutations were selected because of their benefit in at least one environment (Remold and Lenski 2004;Flynn et al 2013;Caudle et al 2014;Cervera et al 2016;Li and Zhang 2018). For example, differences in the fitness landscape comprising five mutations selected during adaptation of tobacco etch potyvirus to a novel host were shown to contribute to trade-offs in fitness on the original host (Cervera et al 2016). Similarly, interactions between mutations in the Plasmodium falciparum dihydrofolate reductase gene predict different patterns of cross-resistance between antimalarial drugs .…”

Viral fitness predicts the magnitude and direction of perturbations in the infected host transcriptome

“…With this experimental set up, fitness is just the relative ability of a viral strain to produce stable infectious progeny in a given host (cell type, organ, individual, or species) when the available resources have to be shared with a competitor 5 .Regardless its limitations, at least, this approach provides a metric for ranking viral strains according to their performance in a particular environment/host. Such a fitness measure has been pivotal for quantitatively understanding many virus evolution processes: the effect of genetic bottlenecks and accumulation of deleterious mutations in RNA virus populations 6-8 , the rates and dynamics of adaptive evolution into novel hosts 9, , the pleiotropic cost of host range expansion 10-12 , the cost of genome complexity 13,14 , the cost of antiviral escape mutations 15-17 , the topography of adaptive fitness landscapes [18][19][20] , and the role of robustness in virus evolution 21-23 .But differences in viral fitness should also matter in genome wide studies seeking to understand the mode of action of the viruses (i.e., the precise way they interact with their hosts).Even though it has been argued that an integrative systems biology approach to viral pathogenesis would result in a better understanding of pathogenesis and in the identification of common targets for different viruses, therefore serving as a guide to a more rational design of therapeutic drugs 24-30 , pioneering studies have ignored the high genetic variability of viruses and subsequent differences in fitness and in mode of action. Experimental evidences support that even single nucleotide substitutions have significant effects on viral fitness, regardless they are synonymous or nonsynonymous, or they affect coding or non-coding genomic regions [31][32][33][34][35][36][37] .…”

“…Regardless its limitations, at least, this approach provides a metric for ranking viral strains according to their performance in a particular environment/host. Such a fitness measure has been pivotal for quantitatively understanding many virus evolution processes: the effect of genetic bottlenecks and accumulation of deleterious mutations in RNA virus populations 6-8 , the rates and dynamics of adaptive evolution into novel hosts 9, , the pleiotropic cost of host range expansion 10-12 , the cost of genome complexity 13,14 , the cost of antiviral escape mutations 15-17 , the topography of adaptive fitness landscapes [18][19][20] , and the role of robustness in virus evolution 21-23 .…”