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tions per nucleotide and per replication round (Drake and Holland, 1999)? If that figure is valid, then how large should both nucleotide and population samples be to detect a significant proportion of its genetic variability? It is expected that the fitness recovery of an expanding population of a highly debilitated clone should be characterized at the molecular level by repeated nonsynonymous substitution fixation, a pattern that has not been observed in the regions studied. If we consider that the estimated number of beneficial mutations in VSV expanding populations is low, then it might be possible that the two regions selected have not been the appropriate ones. This statement points toward a much higher nucleotide sampling. However, as can be seen in Table 6, there is a reduction of the frequency of VSV molecules showing indels in the U-stretch of the intergenic region. As mentioned above, indels in this region have an effect on the levels of transcription of the adjacent genes and can be responsible for the fitness reduction of the MARM F clone. A recent study (Escarmís et al., 1999) on the evolution of highly debilitated foot-and-mouth disease virus clones under continuous population expansions give support to this idea. Escarmís et al. (1999) observed that the original debilitated clone had six-point mutations spread over the genome in addition to an elongated internal polyadenylate tract immediately preceding the second initiation AUG codon (Escarmís et al., 1996). The point mutations were replaced and the polyadenylate tract disappeared after a large number of passages (Escarmís et al., 1999).

QUASISPECIES AND POPULATION GENETICS THEORIES OF THE EVOLUTION OF RNA VIRUSES

There is abundant theoretical literature related to the dynamics of populations in which mutation is a frequent event. This is the case of Eigen and Schuster's notion of quasispecies (Eigen and Schuster, 1977) where the target of selection is no longer a single fittest genotype but rather a cloud of mutants distributed around a most frequent one quoted as master sequence. Following those authors, population genetics theory is a good descriptor for those populations where mutations are rare events and purifying selection is the main evolutionary force generating a homogeneous population, in addition to possible neutral variation fixed by random drift (Nowak and Schuster, 1989). They also suggested that the quasispecies theory is able to handle all situations, from small to large mutation rates. If true, then we have two different theories with different explanatory power, formally being the quasispecies theory of a wider application range than population genetics, in a way similar to the statement that general relativity is more general than Newton's mechanics. However, the theoretical models of population genetics are not compro-



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