The diversity of resistance challenges the ability of pathogens to spread and to exploit host populations. Yet, how this host diversity evolves over time remains unclear because it depends on the interplay between intraspecific competition among host genotypes and coevolution with pathogens. Here we study experimentally the effect of coevolving phage populations on the diversification of bacterial CRISPR immunity across space and time. We demonstrate that the negative-frequency-dependent selection generated by coevolution is a powerful force that maintains host resistance diversity and selects for new resistance mutations in the host. We also find that host evolution is driven by asymmetries in competitive abilities among different host genotypes. Even if the fittest host genotypes are targeted preferentially by the evolving phages, they often escape extinctions through the acquisition of new CRISPR immunity. Together, these fluctuating selective pressures maintain diversity, but not by preserving the pre-existing host composition. Instead, we repeatedly observe the introduction of new resistance genotypes stemming from the fittest hosts in each population. These results highlight the importance of competition on the transient dynamics of host–pathogen coevolution.

耐药性的多样性挑战了病原体传播和利用宿主种群的能力。然而，这种宿主多样性如何随时间演变仍不清楚，因为它取决于宿主基因型之间的种内竞争和与病原体的共同进化之间的相互作用。在这里，我们通过实验研究了共同进化的噬菌体群体对细菌 CRISPR 免疫在空间和时间上的多样化的影响。我们证明了协同进化产生的负频率依赖性选择是维持宿主抗性多样性并选择宿主中新的抗性突变的强大力量。我们还发现宿主进化是由不同宿主基因型之间竞争能力的不对称驱动的。即使进化中的噬菌体优先靶向最适合的宿主基因型，它们经常通过获得新的 CRISPR 免疫来避免灭绝。总之，这些波动的选择压力保持了多样性，但不是通过保留预先存在的宿主组成。相反，我们反复观察到来自每个种群中最适宿主的新抗性基因型的引入。这些结果强调了竞争对宿主 - 病原体共同进化的瞬态动态的重要性。