EVOLUTIONARY DYNAMICS OF FITNESS RECOVERY FROM THE DEBILITATING EFFECTS OF MULLERS RATCHET

The great adaptability shown by RNA viruses is a consequence of their high mutation rates. The evolution of fitness in a severely debilitate d, clonal population of the nonsegmented ribovirus vesicular stomatiti s virus (VSV) has been compared under five different demographic regim es, ranging from severe serial bottleneck passages tone virion) to lar ge population passages (10(6) virions or more) under similar environme ntal conditions (cell culture type and temperature). No matter how sma ll the bottleneck, the fitness of the evolved populations was always h igher than the fitness of the starting population; this result is clea rly different from that previously reported for viruses with higher fi tness. The reattainment of fitness under a regime of serial population passages showed two main characteristics: (1) the rate of adaptation was higher during early passages; and (2) a maximum fitness value was reached after a large number of passages. The maximum fitness reached by this initially debilitated clone was similar to the fitness of wild -type virus. The practical implications of these findings in the desig n of vaccines using attenuated viruses are also discussed.