Mutant cloud

An interesting detail of the quasi-species concept was predicted more than twelve years ago [24] and has been observed recently with virus populations [25] and computer simulations [26] We assume two genotypes of high fitness, each one surrounded by a specific mutant doud (Fig. 2.5). Genotype Iml has higher fitness compared to Im2 but less efficient mutants in the sense of a mutant cloud with lower mean fitness. The quasi-species considered as a function of the mutation rate p may show a rearrangement reminiscent of a phase transition at some critical replication accuracy qa = 1 - pCT. At low mutation rates, p>pCI, the difference in fitness values determines selection and hence, the master sequence with higher fitness, fml, dominates. Above the critical mutation rate, p>pCI, however, mutational backflow to the master is decisive and then fm2 is selected. 

Fig. 2.5. A quasi-species-type mutant distribution around a master sequence. The quasi-species is an ordered distribution of polynucleotide sequences (RNA or DNA) in sequence space. A fittest genotype or master sequence /m, which is commonly present at highest frequency, is surrounded in sequence space by a cloud of closely related sequences. Relatedness of sequences is expressed (in terms of error classes) by the number of mutations which are required to produce them as mutants of the master sequence. In case of point mutations the distance between sequences is the Hamming distance. In precise terms, the quasi-species is defined as the stable stationary solution of Eq. (2) [16,19, 20], In reality, such a stationary solution exists only if the error rate of replication lies below a maximal value called the error threshold. In this region, i.e. below...

S. Ferro-Novick and J. Beckwith, personal communication), can suppress the secretion defect of a secA mutant (Ferro-Novick et al., 1984c). The phenotype of a temperature-sensitive secC mutant is similar to that of a secA strain. At the nonpermissive temperature, synthesis of exported proteins is blocked. The synthesis of MBP can be restored in secC mutants by mutations in the hydrophobic core of its signal sequence. The new insights into SecA mutants (Strauch et al., 1986) cloud the interpretation of thise results. 

We have been principally occupied with that part of the question that deals with the onset of the process, i.e., the initiation and execution of fermentative derepression. To answer the question regarding transcriptional products we have used two approaches (1) determination whether a p mutant lacking mtDNA (p or DNA ) is still capable of derepression this approach is limited to the potentially derepressible entities still present in such a mutant such as cytochrome c or L-malate dehydrogenase (2) the use of EtdBr as a specific inhibitor for transcription this approach is somewhat clouded by reports that this agent, although specific for mitochondrial processes, may inhibit translation as well as transcription. Fortunately, both types of experiments give the same answer there is no evidence for the participation of mitochondrial transcripts in the initiation or execution of the fermentative phase of derepression. The same answer also applies to products of mitochondrial translation which we have assessed by the use of CAP as a specific inhibitor. 

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