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。变异率高达正常水平1000倍的细菌(变种细菌)经常在自然种群中被发现。事实上，一项研究报告称，在囊性纤维症(CF)患者肺部定植的铜绿假单胞菌菌株中，有20%是变种。突变细菌对人类、动物和植物的健康具有重要影响，因为它们比非突变细菌更善于感染新的宿主物种，并可能对甲氧西林等抗生素产生抗药性。然而，目前尚不清楚为什么这些突变细菌会在很长一段时间内保持如此高的频率。我们希望通过调查细菌社会相互作用在决定细菌突变率进化中的作用来采取一种新的方法来解决这个问题。通过了解最终导致细菌突变率上升的原因，有可能控制它们。在大多数情况下，突变细菌应该会很快灭绝，因为大多数基因突变对它们所在的有机体有害。然而，最近的研究表明，高突变率有时可能对生活在应激环境中的细菌有利，因为产生偶尔的突变有助于它们适应应激环境的好处超过了产生破坏性突变的成本。然而，这并不能解释突变菌的长期持久性，因为一旦细菌适应了他们的环境，突变菌就不再具有优势，应该会灭绝。对于变种人来说，环境必须不断变化，才能继续创造紧张的条件。在这里，我们采取了一种新的方法，并解决了与其他有机体的相互作用可能造成不断变化的环境条件，从而使突变体得以持续存在的可能性。我们将考虑两种类型的社交互动。首先，与同一物种的成员的合作和冲突。细菌经常相互合作，例如，通过共同产生清除营养物质的分子。但合作是可以欺骗的：那些获得了所有好处但不支付制造分子成本的个人。突变基因更有效地产生作弊，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。合作者和作弊者(合作者进化以避免被利用，而作弊者进化以避免被利用)之间的这种持续的“军备竞赛”可能会创造出有利于变种人的不断变化的条件。第二，与寄生病毒(噬菌体)的相互作用。噬菌体在体内生长并杀死它们的宿主细菌。当细菌和噬菌体一起进化时，它们也经历了一场军备竞赛，细菌进化出对噬菌体感染的抵抗力，而噬菌体进化来克服这种抵抗力，依此类推。据预测，在与不断进化的噬菌体相互作用时，突变株比非突变株具有优势。我们将使用数学模型和实验相结合的方法来解决这些问题。与大多数有机体不同的是，细菌非常容易接受进化实验。它们的世代时间短(只有30分钟)和庞大的种群规模(在实验室培养中高达100亿)，这意味着它们在几天内进化。此外，细菌可以在悬浮态下储存在冰箱里，通过直接比较不同种群在进化史上的不同点来衡量进化；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.