Department of Biology & Center for Genomics and Systems Biology, New York University, New York, NY, 10003, USA.
Department of Physics, New York University, New York, NY, 10003, USA.
Nat Commun. 2021 Nov 24;12(1):6817. doi: 10.1038/s41467-021-26609-w.
Bacterial defenses against phage, which include CRISPR-mediated immunity and other mechanisms, can carry substantial growth rate costs and can be rapidly lost when pathogens are eliminated. How bacteria preserve their molecular defenses despite their costs, in the face of variable pathogen levels and inter-strain competition, remains a major unsolved problem in evolutionary biology. Here, we present a multilevel model that incorporates biophysics of molecular binding, host-pathogen population dynamics, and ecological dynamics across a large number of independent territories. Using techniques of game theory and non-linear dynamical systems, we show that by maintaining a non-zero failure rate of defenses, hosts sustain sufficient levels of pathogen within an ecology to select against loss of the defense. This resistance switching strategy is evolutionarily stable, and provides a powerful evolutionary mechanism that maintains host-pathogen interactions, selects against cheater strains that avoid the costs of immunity, and enables co-evolutionary dynamics in a wide range of systems.
细菌防御噬菌体的机制，包括 CRISPR 介导的免疫和其他机制，可能会带来显著的生长速度代价，并且在病原体被消除时，这些机制可能会迅速丢失。尽管存在这些成本，但在面对病原体水平和菌株间竞争的变化时，细菌如何保存其分子防御机制仍然是进化生物学中的一个主要未解决问题。在这里，我们提出了一个多层次模型，该模型结合了分子结合的生物物理学、宿主-病原体种群动态以及大量独立领地的生态动态。使用博弈论和非线性动力系统的技术，我们表明，通过维持防御系统的非零失效率，宿主在生态系统中维持足够水平的病原体，以选择不失去防御。这种抵抗转换策略在进化上是稳定的，它提供了一种强大的进化机制，维持了宿主-病原体相互作用，选择了逃避免疫成本的欺骗菌株，并使广泛的系统中的共同进化动力学成为可能。
