Epistasis between mutations is host-dependent for an RNA virus

Jasna Lalić1 and
Santiago F. Elena1,2,*

¹Instituto de Biología Molecular y Celular de Plantas, CSIC-UPV, 46022 València, Spain²Santa Fe Institute, Santa Fe NM 87501, USA

*Author for correspondence (santiago.elena@csic.es).

Abstract

How, and to what extent, does the environment influence the way mutations interact? Do environmental changes affect both the sign and the magnitude of epistasis? Are there any correlations between environments in the variability, sign or magnitude of epistasis? Very few studies have tackled these questions. Here, we addressed them in the context of viral emergence. Most emerging viruses are RNA viruses with small genomes, overlapping reading frames and multifunctional proteins for which epistasis is abundant. Understanding the effect of host species in the sign and magnitude of epistasis will provide insights into the evolutionary ecology of infectious diseases and the predictability of viral emergence.

1. Introduction

The large majority of emerging viruses are RNA viruses [1]. However, their compact genomes comprising overlapping reading frames and multifunctional proteins and their high mutation rates may impose severe adaptive constraints [2]. Understanding the mechanistic basis of these constraints is central to explaining why some RNA viruses are more able than others to cross species boundaries. Epistasis is thought to be important in the evolution of host range [3,4]. Moreover, it has been suggested that the sign of epistasis depends on environmental severity, switching from positive to negative as environments become stressful [5]. Yet, few studies have empirically examined this possibility.

To evaluate the effect that different hosts exert on the distribution of epistatic interactions, we tested the fitness of Tobacco etch virus (TEV) genotypes carrying two single-nucleotide substitutions, whose independent effects were previously evaluated [6], across susceptible hosts of increasing genetic divergence from the primary host. TEV naturally infects Solanaceae plants, and the strain used here was isolated from Nicotiana tabacum [7]. Previously, we have shown that the deleterious effects of mutations were stronger as the host (i.e. the virus’s environment, E) was more genetically diverged from tobacco, and the proportion of lethal, deleterious, neutral and beneficial mutations was also altered [6]. We also found that this host dependence (i.e. plasticity or G ×E) had two origins: antagonistic pleiotropy and changes in genetic variance for fitness across hosts [6]. Furthermore, we recently found that the fitness effect of a given mutation depended on the genetic background where it was evaluated (i.e. epistasis or G × G) [8]. Variation was observed both in the sign and the strength of epistasis, being negative on average and with abundant cases of reciprocal sign epistasis [8]. If G × E and G × G play major roles in determining TEV fitness, it is logical to expect that epistasis may also vary depending on environmental severity [9], that is, a G × G × E component may exist. Quantifying the extent to which G × G × E determines viral fitness is central to predicting the fate of viral genotypes across hosts and, ultimately, the likelihood that viruses will cross host species barriers. Epistatic interactions allowing RNA viruses to infect new hosts have been widely observed. For example, interactions between five amino acids in the coat protein of Pelargonium flower break virusare necessary for improving fitness in the new host Chenopodium quinoa [10]. Similarly, the ability of Potato virus Y to infect resistant pepper plants depends both on the alleles at the VPg and at the CI genes [11].

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Jasna Lalić, & Santiago F. Elena (2012). Epistasis between mutations is host-dependent for an RNA virus Biology letters DOI: 10.1098/rsbl.2012.0396

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Epistasis between mutations is host-dependent for an RNA virus.