J. theor. Biol. (1989) 138, 407-412 LETrER TO THE EDITOR On The Evolution of Sex in RNA Viruses This letter discusses The evolution of sex in RNA viruses by Chao (1988) which suggests that many viral genetic phenomena can be understood as adaptations to reduce mutation load. In the first section I will discuss his interpretation and presentation of empirical results. In the second section I will discuss his theoretical framework. Multicomponent viruses and retroviruses are discussed in the final section. When viruses are cultured under conditions of high multiplicity serial passage, it is commonly observed that "defective interfering" (DI) viruses rise to high frequencies (De Polo et al., 1987; Huang & Baltimore, 1977; Huang, 1973). These DI viruses are mutant viruses which are deficient in essential functions but which enjoy a selective advantage in the context of high multiplicity serial passage where their deficiencies can be masked by other genomes coding for complementing proteins. For example, the DI virus of poliovirus studied by Cole & Baltimore (1973) contains a deletion in the gene coding for capsid protein. The reasons for the selective advantage of DI viruses are varied (Re & Kingsbury, 1988; Holland, 1985); simply being shorter may itself be an advantage if this results in faster replication. The amplification of DI viruses has many consequences for virus titer, infectiousness and virulence, typically lowering all three. (For interesting guides to the literature see Holland et al., 1982; De Polo et al., 1987.) The amplification of DI viruses is sometimes referred to as the "yon Magnus effect" after his description and explana- tion of the phenomenon in influenza viruses under high multiplicity serial passage (von Magnus, 1954). But, according to Chao, the experimental results of von Magnus are not due to the yon Magnus effect at all, but are due to the progressive accumulation of deleterious mutations which interact in a "synergistic" fashion, i.e. the (n+ 1)th mutation decreases infectivity more than the nth. This is a revolutionary idea which, if true, necessitates the complete reanalysis of a substantial body of data and renders a whole literature obsolete. It is remarkable that Chao does not acknowledge the novelty of the idea, or attempt to justify it, since yon Magnus clearly states that the amplification of defective virus he observed was not due to the degeneration of fully active virus, but was a product of virus multiplication distinct from the infective virus (von Magnus, 1954, p. 60). DI viruses are typically deletion mutants. Younger et al. (1981) studied the increase in frequency of both DI viruses and temperature sensitive (ts) point mutants in vesicular stomatitis virus under conditions of high multiplicity serial passage. Younger et al. (1981) suggested that their ts mutant results may be due to either (i) the amplification ofts mutants present at low frequency in the original inoculum, or (ii) the accumulation of ts mutations. Chao implicitly claims that the second 407 0022-5193/89/110407+06 $03.00/0 O 1989 Academic Press Limited