Synchronous Loss of Quasispecies Memory in Parallel Viral Lineages: A Deterministic Feature of Viral Quasispecies

Ruiz-Jarabo, C.M.; Miller, E.; Gómez-Mariano, G.; Domingo, E.

Journal of Molecular Biology 333(3): 553-563


ISSN/ISBN: 0022-2836
PMID: 14556744
DOI: 10.1016/j.jmb.2003.08.054
Accession: 009991512

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Viral quasispecies are endowed with a memory of their past evolutionary history in the form of minority genomes of their mutant spectra. To determine the fate of memory genomes in evolving viral quasispecies, we have measured memory levels of antigenic variant of foot-and-mouth disease virus (FMDV) RED, which includes an Arg-Glu-Asp (RED) at a surface antigenic loop of the viral capsid. The RED reverted to the standard Arg-Gly-Asp (RGD), and the RED remained as memory in the evolving quasispecies. In four parallel evolutionary lineages, memory reduction followed a strikingly similar pattern, and at passage 60 memory levels were indistinguishable from those of control populations (devoid of memory). Nucleotide sequence analyses indicated that memory loss occurred synchronously despite its ultimate molecular basis being the stochastic occurrence of mutations in the evolving quasispecies. These results on the kinetics of memory levels have unveiled a deterministic feature of viral quasispecies. Molecular mechanisms that may underlie synchronous memory loss are the averaging of noise signals derived from mutational input, and constraints to genome diversification imposed by a nucleotide sequence context in the viral genome. Possible implications of the behaviour of complex, adaptive viral systems as experimental models to address primary mechanisms of neurological memory are discussed. Reprinted by permission of the publisher.