Social interactions and the evolution of bacterial mutation rates

社会互动和细菌突变率的演变

• 批准号: NE/D014115/1
• 负责人: Angus Buckling
• 金额: $ 32.42万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=NE%2FD014115%2F1
• 关键词: Social; interactions; evolution; bacterial; mutation

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.

突变是生物体遗传物质（DNA）的自发变化。在天然种群中经常发现突变率高达1000倍（“突变器”细菌）的细菌。实际上，一项研究报告说，铜绿假单胞菌菌株中有20％的菌株在患有囊性纤维蛋白（CF）的患者的肺中定居（CF）是突变器。突变细菌对人，动物和植物健康具有重要意义，因为它们在感染新宿主物种方面比非杂种剂更好地感染了新宿主物种，并且可以发展对抗生素的抗药性。但是，目前尚不清楚为什么这些突变细菌在如此高的频率上长时间持续存在。我们希望通过研究细菌社会相互作用在确定细菌突变速率演变中的作用来采用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升高的原因，可以控制它们。在大多数情况下，突变细菌应该迅速死亡，因为大多数遗传突变对它们所发生的生物都是不利的。但是，最近的研究表明，当突变率升高可能对生活在压力环境中的细菌有益，而当偶尔产生偶尔的突变的益处可以帮助它们适应压力环境，使压力环境适应产生的损害造成的破坏性突变的成本。但是，这并不能解释突变器的长期持久性，因为一旦细菌适应其环境，突变器细菌将不再具有优势并应消失。为了使突变器持续存在，环境必须不断变化，以继续产生压力条件。在这里，我们采用了一种新颖的方法，并解决了与其他生物体相互作用的可能性，可能会造成不断变化的环境状况，从而使突变器能够持续存在。我们将考虑两种类型的社交互动。首先，合作与与同一物种成员的冲突。细菌经常相互配合，例如通过共同产生清除营养的分子。但是合作对作弊开放：获得所有收益但不支付制作分子的费用的个人。突变器基因型会更有效地产生作弊，并且更有可能找到克服合作者方法以避免被欺骗剥削的新颖方法。合作者和作弊者之间的这种不断的“手臂种族”（合作者不断发展以避免被剥削，而作弊以开发的作弊）可能会产生不断变化的条件，从而有利于突变器。其次，与寄生病毒（噬菌体）的相互作用。噬菌体在里面生长并杀死他们的宿主细菌。当细菌和噬菌体一起发展时，它们还会发生武器种族，从而通过噬菌体进化了对感染的抗性，并且噬菌体会进化以克服这种抗性，依此类推。预计突变器与不断发展的噬菌体相互作用时具有比非突变器具有优势。我们将使用数学模型和实验的结合来解决这些问题。与大多数生物不同，细菌高度适合进化实验。他们短期的时间（仅30分钟）和大量人口（在实验室文化中最多100亿）意味着它们会在几天之内发展。此外，细菌可以存储在冰箱中的悬浮动画中，从而可以通过直接比较其进化史中不同点的不同种群来测量进化；有效地是活化的化石记录。