Department of Biology, University of Washington, Box 351800, Seattle, WA 98195, USA.
Philos Trans R Soc Lond B Biol Sci. 2010 Aug 27;365(1552):2503-13. doi: 10.1098/rstb.2010.0066.
Understanding pathogen infectivity and virulence requires combining insights from epidemiology, ecology, evolution and genetics. Although theoretical work in these fields has identified population structure as important for pathogen life-history evolution, experimental tests are scarce. Here, we explore the impact of population structure on life-history evolution in phage T4, a viral pathogen of Escherichia coli. The host-pathogen system is propagated as a metapopulation in which migration between subpopulations is either spatially restricted or unrestricted. Restricted migration favours pathogens with low infectivity and low virulence. Unrestricted migration favours pathogens that enter and exit their hosts quickly, although they are less productive owing to rapid extirpation of the host population. The rise of such 'rapacious' phage produces a 'tragedy of the commons', in which better competitors lower productivity. We have now identified a genetic basis for a rapacious life history. Mutations at a single locus (rI) cause increased virulence and are sufficient to account for a negative relationship between phage competitive ability and productivity. A higher frequency of rI mutants under unrestricted migration signifies the evolution of rapaciousness in this treatment. Conversely, spatially restricted migration favours a more 'prudent' pathogen strategy, in which the tragedy of the commons is averted. As our results illustrate, profound epidemiological and ecological consequences of life-history evolution in a pathogen can have a simple genetic cause.
了解病原体的感染性和毒力需要结合流行病学、生态学、进化和遗传学的见解。尽管这些领域的理论工作已经确定了种群结构对病原体生活史进化的重要性，但实验测试却很少。在这里，我们探讨了种群结构对大肠杆菌噬菌体 T4 生活史进化的影响。该宿主-病原体系统以集合种群的形式传播，其中亚种群之间的迁移受到限制或不受限制。限制迁移有利于感染率和毒力低的病原体。不受限制的迁移有利于快速进入和离开宿主的病原体，尽管由于宿主种群的迅速灭绝，它们的生产力较低。这种“掠夺性”噬菌体的兴起产生了“公地悲剧”，其中更好的竞争者降低了生产力。我们现在已经确定了掠夺性生活史的遗传基础。单一基因座（rI）的突变导致毒力增加，足以解释噬菌体竞争能力和生产力之间的负相关关系。在不受限制的迁移下，rI 突变体的频率更高，表明在这种处理下出现了掠夺性。相反，受限制的空间迁移有利于更“谨慎”的病原体策略，从而避免了公地悲剧。正如我们的结果所表明的，病原体生活史进化所带来的深远的流行病学和生态学后果可能有一个简单的遗传原因。
