Virus-host arms race at the joint origin of multicellularity and programmed cell death

Abstract

Unicellular eukaryotes and most prokaryotes possess distinct mechanisms of programmed cell death (PCD). How an "altruistic" trait, such as PCD, could evolve in unicellular organisms? To address this question, we developed a mathematical model of the virus-host co-evolution that involves interaction between immunity, PCD and cellular aggregation. Analysis of the parameter space of this model shows that under high virus load and imperfect immunity, joint evolution of cell aggregation and PCD is the optimal evolutionary strategy. Given the abundance of viruses in diverse habitats and the wide spread of PCD in most organisms, these findings imply that multiple instances of the emergence of multicellularity and its essential attribute, PCD, could have been driven, at least in part, by the virus-host arms race.

Keywords: AI, abortive infection; PCD, programmed cell death; TA, toxin-antitoxin; evolution of multicellularity; host-parasite arms race; programmed cell death; viruses.

Figure 1.

Programmed cell death provides multicellular clusters, but not singletons, with a fitness advantage. The fitness of hosts that form multicellular clusters (A, p_m = 0.05, characteristic cluster size of 5-6 hosts) and singletons (B, p_m = 1) is calculated as a function of the suicide probability. Different curves correspond to increasing values of the pathogen arrival rate a, with top-to-bottom increments of 0.3 between consecutive curves.

Figure 2.

Fitness landscapes associated to the probabilities of host suicide and migration. As the pathogen arrival rate increases, the higher fitness peak transitions from the unicellular state with no suicide (p_m = 1, p_s = 0) to the multicellular state with the highest suicide probability (p_m = 0.05, p_s = 1). The red line shows the evolutionary trajectory with the minimum fitness loss connecting the 2 fitness peaks. Black areas indicate a cutoff in the plot.

Figure 3.

Exposure to pathogens determines the evolutionary outcome. Top: In blue (red), mean fitness of a population of hosts that self-organize in multicellular (unicellular) clusters with (without) programmed cell death. Bottom: Mean cluster size for the same populations. The continuous line indicates the expected cluster size if both classes of hosts compete. When the pathogen arrival rate is greater than 3.2, both classes of hosts become extinct.

Figure 4.

Outcome of the competition between the 2 extreme classes of hosts (p_m = 0.05, p_s = 1; and p_m = 1, p_s = 0) as a function of the pathogen pressure, a, and the growth scale exponent, ${\displaystyle \text{γ}}$. Values of ${\displaystyle \text{γ}}$ close to one expand the range of pathogen arrival rates that lead to the multicellular state.

Figure 5.

Suicide and immunity are not equivalent. In blue (red), mean fitness of a population of hosts that self-organize in multicellular (unicellular) clusters, as a function of the immune probability p_i (top) and the suicide probability p_s (bottom). Pathogen arrival rate a = 2.

Figure 6.

Effect of immunity on the evolution of multicellularity. (A) The fitness of hosts with p_m = 0.05 (multicellular organization) and variable suicide and immune probabilities (p_i on the x-axis, p_s on the y-axis) is compared to those of hosts with p_m = 1 (singletons), same immune probability and no suicide. The border between red and blue regions indicates the minimum suicide probability required for multicellularity to evolve. Pathogen arrival rate a = 2. (B) Evolutionary outcomes for different values of the pathogen arrival rate and the immune probability, with the suicide probability of multicellular hosts fixed to p_s = 1. The border between the blue and gray regions shows the pathogen arrival rate that leads to the extinction of the host at different immune probabilities.