The research published today in Journal of Biology examines how mutant bacteria respond to different forms of stress, from cold temperature to the inhibition of protein synthesis. Prof. Stanislas Leibler and Dr. Roy Kishony found that, on average, mutants fare better when they are stressed.
"In contrast to the perception that stress always reduces the organism's ability to tolerate mutations, our measurements identified stresses that do the opposite – that is, despite decreasing wild-type growth, on average they alleviate the effect of deleterious mutation," write the authors.
The scientists measured the 'fitness' of 65 E. coli strains carrying individual mutations and 12 control strains under normal and stressful conditions, by calculating their growth rates. To do this they developed a method that is a thousand times more sensitive than current methods at measuring bacterial growth rates. All the bacterial strains tested were engineered so that they produced an enzyme from fireflies called luciferase, which emits light. The number of bacteria in a population could then be counted by measuring how much light those bugs emitted. Comparing the rates of growth of control and mutant cells under the different environmental conditions showed that on average, the difference in growth rate was smaller when the bacteria were stressed.
The advantage of sexual reproduction is widely held to be that it allows harmful mutations to be efficiently purged from the genome. Recombination of DNA during sexual reproduction splits up pairs of mutations, increasing the fitness of any progeny. For this to be an evolutionary advantage, the effect of two harmful mutations must be additive, or worse.
Two of the stressful conditions studied by Kishony and Leibler involved treating mutant bacterial cells with antibiotics that specifically target one molecular pathway. This is similar to introducing a second mutation into those cells. Yet on average the stress had far less impact on the growth rate of mutant cells than on that of wild type cells. If the stress (the second mutation) leads to a defined decline in growth rate, this observation suggests that the second mutation reduces the negative effect of the first. The authors also looked at this result in another way. By drawing a graph showing the decline in growth rate under normal and adverse conditions, as the number of mutations in the bacteria increased they could see that the slope of the line for growth under stressful conditions was shallowest. These results were extrapolated to see what would happen when the bugs contained increasing numbers of mutations. In doing this, the researchers assumed that increasing the number of mutations increased the severity of their combined effect in a linear logarithmic fashion. When they did this the lines crossed. This "…would imply that, on average, the stress increases the absolute growth rate of bacteria carrying enough random mutations". As this possibility is "unrealistic", the authors suggest instead that increasing the number of mutations does not increase the severity of their effect in this way, but that together the mutations are less harmful than they would be if their effect was additive.
Most higher organisms reproduce sexually, despite the obvious advantages of asexual reproduction, such as the higher percentage of the population that can reproduce. This means that there must be selective forces that confer an advantage on sexuality and genetic recombination. The new research from Kishony and Leibler suggests that this advantage may not be as simple as genetic recombination effectively removing harmful mutations from a genome.
This article is freely available online, according to BioMed Central's policy of open access to research articles:
Environmental stresses can alleviate the average deleterious effect of mutations
Roy Kishony and Stanislas Leibler
Journal of Biology 2003: 2:14
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