Evolutionary dynamics of genome segmentation in multipartite viruses

Abstract

Multipartite viruses are formed by a variable number of genomic fragments packed in independent viral capsids. This fact poses stringent conditions on their transmission mode, demanding, in particular, a high multiplicity of infection (MOI) for successful propagation. The actual advantages of the multipartite viral strategy are as yet unclear. The origin of multipartite viruses represents an evolutionary puzzle. While classical theories suggested that a faster replication rate or higher replication fidelity would favour shorter segments, recent experimental results seem to point to an increased stability of virions with incomplete genomes as a factor able to compensate for the disadvantage of mandatory complementation. Using as main parameters differential stability as a function of genome length and MOI, we calculate the conditions under which a set of complementary segments of a viral genome would outcompete the non-segmented variant. Further, we examine the likeliness that multipartite viral forms could be the evolutionary outcome of the competition among the defective genomes of different lengths that spontaneously arise under replication of a complete, wild-type genome. We conclude that only multipartite viruses with a small number of segments could be produced in our scenario, and discuss alternative hypotheses for the origin of multipartite viruses with more than four segments.

Figure 1.

Schematic of the infective process. The MOI is the (average) number of viral particles infecting a cell. Incomplete genomes (Δ1 and Δ2) have an average lifetime that is larger than that of the wt between infective events, as shown graphically by the decrease in number of the wt relative to genomes with deletions. The process is iterated until the equilibrium state is attained.

Figure 2.

Evolutionary outcomes for the competition between a single particle virus (wt) and its bipartite variant (Δ1 and Δ2). (a,b) Equilibrium points in the population simplex (open circles, unstable; filled circles, stable); arrows indicate the evolutionary trajectories. (c,d) Temporal evolution of population composition for a characteristic realization (filled circles: wt, open circles: Δ1 and Δ2, legend for each viral form as in the previous figure). (a,c) Fixation of the bipartite variant takes place if survival of the wt is below a critical value σ < σ_crit. (b,d) Coexistence of all viral classes occurs if σ > σ_crit. An analytical expression for σ_crit is given in the main text.

Figure 3.

Evolutionary regions depending on selective pressures (MOI and degradation of wt class). Regions corresponding to coexistence and extinction of wt (fixation of bipartite virus) are separated by a series of critical points, whose values vary slightly according to the probability distribution that governs the infection process (solid circles, multinomial; open squares, Poisson, dashed line, asymptotic behaviour).

Figure 4.

Evolutionary outcomes for genomes with multiple segments. (a) Coexistence and multipartite fixation regions for three segments. Rectangles schematically indicate the number of segments that viral classes contain in a certain region (all classes with such a number of segments will be present). Compare these curves with σ_crit for two segments, shown in figure 3. (b) Critical value of the MOI required for fixation of single-segment classes (thick line on the left), for σ = 0.5. Other lines indicate further transitions: from double-single coexistence to triple-double-single, and so on.