The coevolution of virulence: tolerance in perspective

Abstract

Coevolutionary interactions, such as those between host and parasite, predator and prey, or plant and pollinator, evolve subject to the genes of both interactors. It is clear, for example, that the evolution of pollination strategies can only be understood with knowledge of both the pollinator and the pollinated. Studies of the evolution of virulence, the reduction in host fitness due to infection, have nonetheless tended to focus on parasite evolution. Host-centric approaches have also been proposed--for example, under the rubric of "tolerance", the ability of hosts to minimize virulence without necessarily minimizing parasite density. Within the tolerance framework, however, there is room for more comprehensive measures of host fitness traits, and for fuller consideration of the consequences of coevolution. For example, the evolution of tolerance can result in changed selection on parasite populations, which should provoke parasite evolution despite the fact that tolerance is not directly antagonistic to parasite fitness. As a result, consideration of the potential for parasite counter-adaptation to host tolerance--whether evolved or medially manipulated--is essential to the emergence of a cohesive theory of biotic partnerships and robust disease control strategies.

Figure 1. The importance of intercepts: point versus range tolerance.

To understand differing interpretations of the evolutionary consequences of tolerance, it is necessary to consider when point and range tolerance will disagree. Below is one scenario where they will agree, and two where they may not. (A) With fitness in the absence of infection identical, at whichever parasite density measured, the fitness of the genotype with the flatter slope will be higher; here, genotype a₁ is more tolerant than b₁ regardless of how it is assessed. Both point and range tolerance measures therefore agree over the more tolerant genotype. (B) Here genotypes differ for their intercept, and the genotype with the higher point tolerance differs depending on whether parasite density is measured at d1 (where b₂>a₂) or d2 (where a₂>b₂). The fitness at d1 is strongly influenced by fitness in the absence of infection, while fitness at d2 is more strongly influenced by how fitness declines with increasing I. Under range tolerance, however, a₂ is more tolerant, despite the fact that it is less (point) tolerant at low densities. (C) Here the point tolerance is always higher for a₃, but the range tolerance depends upon the range of I considered; if tolerance is measured across the range depicted by d1, genotype b₃ would be considered less tolerant, but it would be considered more tolerant if the range measured was d2. Genotype b₃ is always less fit, however.

Figure 2. The importance of intercepts: pleiotropy.

Host genotypes will almost certainly show differences in ω_o,n (genetic variation for life history characteristics is ubiquitous [37]), and in some cases these differences will be linked to variation in the traits that contribute to virulence (α_n or I _n) via pleiotropy (where one gene influences more than one trait). For example, hosts that possess alleles that confer more potent defences (ability to control I or α) may be less fit when parasites are not around because the allele that aids defence compromises the performance of other traits (compare ω_oR and ω_oS; R denotes resistance, S denotes susceptible). In other words, there may be a cost of possessing a defence mechanism , often referred to as a trade-off. It is even conceivable that ω_o,n is lower than host fitness at low I, because individuals without enough parasites can experience difficulty with immune regulation: the hygiene hypothesis posits that allergy and autoimmunity result from immune systems lacking direction from parasites (; see ω_oH, which denotes hygiene). Thus, the rank order of ω_o,n may be the opposite of the rank order of fitness when infected. Moreover, ω_on may not be easily predicted from the relationship between parasite density and host fitness when infected—for example, when just a small number of parasites stimulates a damaging or energy-sapping immune response that is little amplified by further infection. Generally, the fitness of uninfected individuals need not be a linear extrapolation of the relationship between fitness and parasite density (I).