Defective Interference in the Killer System of Saccharomyces cerevisiae

Abstract

The K 1 killer virus (or plasmid) of Saccharomyces cerevisiae is a noninfectious double-stranded RNA genome found intracellularly packaged in an icosahedral capsid. This genome codes for a protein toxin and for resistance to that toxin. Defective interfering virus mutants are deletion derivatives of the killer virus double-stranded RNA genome; such mutants are called suppressive. Unlike strains carrying the wild-type genome, strains with these deletion derivatives are neither toxin producers nor toxin resistant. If both the suppressive and the wildtype virus are introduced into the same cell, most progeny become toxin-sensitive nonkillers (J. M. Somers, Genetics 74 :571-579, 1973). Diploids formed by the mating of a killer with a suppressive strain were grown in liquid culture, and RNA was extracted from samples taken up to 41 generations after the mating. The ratio of killer RNA to suppressive RNA decreased with increasing generations; by 41 generations the killer RNA was barely detectable. The copy numbers of the suppressive genome and its parental killer were virtually the same in isogenic strains, as were the growth rates of diploid strains containing either virus alone. Therefore, suppressiveness, not being due to segregation or overgrowth by faster growing segregants, is likely due to preferential replication or maintenance of the suppressive genome. Three suppressive viruses, all derivatives of the same killer virus (T. K. Sweeney et al., Genetics 84: 27-42, 1976), did not coexist stably. The evidence strongly indicates that the largest genome of the three slowly suppressed both of the smaller genomes, showing that larger genomes can suppress smaller ones and that suppression can occur between two suppressives. Of 48 isolates of strains carrying the suppressive viruses, 5 had newly detectable RNA species, all larger than the original suppressive genomes. At least seven genes necessary for maintenance of the wild-type killer virus ( MAK genes) were needed by a suppressive mutant. No effect of ski mutations (affecting regulation of killer virus double-stranded RNA replication) on suppressiveness was observed.

Adaptive evolution of nontransitive fitness in yeast

“…Notably, the two populations that possess these deletion mutants also possess full-length viral variants. The deletion mutants we observe are similar to the ScV-S defective interfering particles that have been shown to outcompete full-length virus presumably due to their decreased replication time (Kane et al 1979, Ridley and Wickner 1983, Esteban and Wickner 1988).…”

“…Here we describe an alternative mechanism for the success of positive frequency-dependent mutations through multilevel selection of the host genome and a toxin-encoding intracellular virus. The likelihood of such a scenario occurring is aided by the large population size of the extrachromosomal element: each of the ~10 5 cells that comprise each yeast population contains ~10 2 viral particles (Bostian et al 1983, Ridley andWickner 1983).…”

“…These defective interfering particles are thought to outcompete full-length virus due to their decreased replication time (Kane et al 1979, Ridley and Wickner 1983, Esteban and Wickner 1988. Defective interfering particles are common to RNA viruses (Holland et al 1982).…”

A deletion mutant of L-A double-stranded RNA replicates like M1 double-stranded RNA

“…Deletion mutants of M1 dsRNA lacking the toxin immunity precursor coding region have been described (5,6,10,12). These mutants (called S dsRNAs) interfere with (suppress) the replication of the wild-type M1 genome (9,10). S dsRNAs, therefore, are analogous to defective interfering virus particles, the deletion mutants of animal viruses that limit replication of the standard virus during coinfection (for a review, see reference 19).…”

Viruses of Fungi and Protozoans: Is Everyone Sick?

“…Suppressive sensitive mutants (Somers, 1973) of ScV contain L1 and smaller, or S, dsRNAs (Sweeny et al, 1976;Vodkin, 1977). These are defective interfering versions of M1 that are derived from M1 by internal deletion, sometimes followed by tandem duplication (Bruenn and Kane, 1978;Bruenn and Brennan, 1980;Fried and Fink, 1978;Huan et al, 1991;Kane et al, 1979;Lee et al, 1986;Ridley and Wickner, 1983;Thiele et al, 1984). DI segments of rotaviruses have a similar structure (Scott et al, 1989).…”