REPRODUCIBLE NONLINEAR POPULATION-DYNAMICS AND CRITICAL-POINTS DURINGREPLICATIVE COMPETITIONS OF RNA VIRUS QUASI-SPECIES

RNA virus evolution is generally considered to be highly unpredictable , but tests of determinism in the evolution of competing populations d uring viral infections have not been performed. Here we study the fate of two closely related evolving quasispecies: of vesicular stomatitis virus, by determining the relative concentration of a wild-type clone and a surrogate marked virus subclone (MARM-C) upon extensive competi tive replication in a constant cell culture environment. A highly pred ictable nonlinear behaviour of the two competing populations was found . In addition, the presence of critical points, which are defined as p oints from which viral competitions may follow different trajectories, has been documented. Critical points were reached after nearly consta nt periods of time. The dynamics of relative fitness values for both c ompeting populations were calculated during the replication passages. Concomitant with expected fitness gain of both competing viral populat ions (which follow the Red Queen hypothesis) a tendency for the MARM-C to gain less fitness than the wild-type was observed. Although fitnes s variations were noisy, this tendency was seen in all evolutionary re plicas. Thus, despite the stochastic process of mutation that leads to a continuous generation of mutant genomes during RNA virus replicatio n, a nonlinear, nearly deterministic evolutionary behaviour has been o bserved. It is proposed that such a behaviour is mediated by a low-pas s filter (averaging of mutational noise signals) due to competitive se lection among variants. (C) 1996 Academic Press Limited