Social interactions and the evolution of bacterial mutation rates

Mutations are spontaneous changes in the genetic material (DNA) of organisms. Bacteria with mutation rates up to 1000 times higher than normal ('mutator' bacteria) are frequently found in natural populations. Indeed, one study reported that 20% of strains of the pathogenic bacteria Pseudomonas aeruginosa colonising the lungs of patients suffering from cystic fibroses (CF) were mutators. Mutator bacteria have important implications for human, animal and plant health, because they are better at infecting new host species and can evolve resistance to antibiotics, such as methicillin, than non-mutators. However, it is currently unclear why these mutator bacteria persist at such high frequencies for long periods of time. We want to take a novel approach to this problem by investigating the role that bacterial social interactions have in determining the evolution of mutation rates of bacteria. By understanding what ultimately causes elevated bacterial mutation rates, it may be possible to control them. Under most circumstances, mutator bacteria should rapidly die out because most genetic mutations are bad for the organism they occur in. However recent studies suggest that elevated mutation rates may sometimes be beneficial to bacteria living in stressful environments, when the benefit of producing the occasional mutation that helps them to adapt to stressful environments outweighs the cost of producing damaging mutations. However, this doesn't explain the long term persistence of mutators, because as soon as bacteria adapt to their environment, mutator bacteria will no longer have an advantage and should die out. For mutators to persist, the environment must be constantly changing, to keep on creating stressful conditions. Here we take a novel approach and address the possibility that it is interactions with other organism that might create the constantly changing environmental condition that would allow mutators to persist. We will consider two types of social interactions. First, cooperation and conflict with members of the same species. Bacteria often cooperate with each other, for example by communally producing molecules that scavenge nutrients. But cooperation is open to cheats: individuals that gain all the benefits but don't pay the cost of making molecules. Mutator genotypes generate cheats more efficiently, and are more likely to find novel ways of overcoming cooperators' methods to avoid being exploited by cheats. This continual 'arm race' between cooperators and cheats (cooperators evolving to avoid being exploited, and cheats evolving to exploit) may create the constantly changing conditions that could favour mutators. Second, interactions with parasitic viruses (phages). Phages grow inside and kill their host bacteria. When bacteria and phages evolve together, they also undergo an arms race whereby bacteria evolve resistance to infection by phages, and phages evolve to overcome this resistance, and so on. Mutators are predicted to have an advantage over non-mutators when interacting with the constantly evolving phages. We will address these questions using a combination of mathematical models and experiments. Unlike most organisms, bacteria are highly amenable to evolution experiments. Their short generation times (as little as 30 minutes) and massive population sizes (up to 10 billion in a laboratory culture) means they evolve over a matter of days. Furthermore, bacteria can be stored in suspended animation in a freezer, allowing evolution to be measured by directly comparing different populations from different points in their evolutionary history; effectively, a living fossil record.