Social interactions and the evolution of bacterial mutation rates

突变是生物体遗传物质（DNA）的自发变化。突变率比正常细菌高1000倍的细菌（“突变”细菌）经常在自然种群中发现。事实上，一项研究报告说，20%的致病性细菌铜绿假单胞菌菌株定植在患有囊性纤维化（CF）的患者的肺部是突变体。突变细菌对人类、动物和植物健康具有重要意义，因为它们比非突变细菌更善于感染新的宿主物种，并且可以进化出对甲氧西林等抗生素的耐药性。然而，目前还不清楚为什么这些增变细菌长时间以如此高的频率存在。我们希望通过研究细菌社会相互作用在决定细菌突变率进化中的作用来解决这个问题。通过了解最终导致细菌突变率升高的原因，有可能控制它们。在大多数情况下，突变细菌会迅速灭绝，因为大多数基因突变对它们所在的生物体都是有害的。然而，最近的研究表明，突变率的提高有时可能对生活在压力环境中的细菌有益，因为偶尔产生有助于它们适应压力环境的突变的好处超过了产生破坏性突变的成本。然而，这并不能解释突变体的长期存在，因为一旦细菌适应了它们的环境，突变体细菌将不再具有优势，并且应该灭绝。为了让变异体持续存在，环境必须不断变化，不断创造压力条件。在这里，我们采取了一种新的方法，并解决了这样一种可能性，即与其他生物体的相互作用可能会创造出不断变化的环境条件，使突变体得以持续存在。我们将考虑两种类型的社会互动。第一，与同类成员的合作与冲突。细菌经常相互合作，例如通过共同产生吸收营养的分子。但是合作对骗子是开放的：个人获得所有的好处，但不支付制造分子的成本。突变基因型更有效地产生作弊，并且更有可能找到新的方法来克服合作者的方法，以避免被作弊者利用。这种合作者和作弊者之间持续不断的“军备竞赛”（合作者进化以避免被利用，作弊者进化以利用）可能会创造出不断变化的条件，从而有利于突变者。第二，与寄生病毒的相互作用。噬菌体在里面生长并杀死它们的宿主细菌。当细菌和细菌一起进化时，它们也经历了一场军备竞赛，细菌进化出对细菌感染的抵抗力，而细菌进化出克服这种抵抗力的能力，等等。我们将结合数学模型和实验来解决这些问题。与大多数生物不同，细菌非常适合进化实验。它们的短世代时间（只有30分钟）和巨大的种群规模（在实验室培养中高达100亿）意味着它们在几天内进化。此外，细菌可以假死状态储存在冰箱里，这样就可以通过直接比较不同种群在进化史上的不同时间点来衡量进化;实际上，这是一个活化石记录。

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.