The negative effect of permanent contamination of populations because of spontaneous mutations does not appear to be very high if judged from the relatively good health of humans or many wild and domesticated species. This is partly explained by the fact that, in diploids, the new mutations are usually located in heterozygous loci and therefore are masked by wild-type alleles. The expression of mutations at the phenotypic level may also strongly depend on environmental factors if. for example. deleterious alleles are more easily compensated under favorable conditions. The present ex- periment uses diploid strains of yeast in which mutations arise at high rates because a mismatch-repair protein is missing. This mutagenesis resulted in a number of new alleles that were in heterozygous loci. They had no detectable effect on fitness when the environment was benign. A very different outcome was seen when thermal shock was applied, where fitness of the mutation- contaminated clones was lower and more diverse than that of the nonmutagenized clones. This shows that the genetic load con- ferred by spontaneous mutations can be underestimated or even overlooked in favorable conditions. Therefore, genetic variation can be higher and natural selection more intense when environ- mental conditions are getting poorer. These conclusions apply, at least, to that component of variation that directly originates from spontaneous mutations (as opposed to the variation resulting from the history of selection).
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