The evolutionary ecology of CRISPR-Cas adaptive immunity

Abstract

Microbial communities play a vital role in shaping their local environment and provide many important ecosystem services. The structure and function of microbial communities is dependent on interactions with prokaryote-specific viruses and other mobile genetic elements (MGEs), but we know relatively little about these interactions in nature. The prokaryotic adaptive immune system CRISPR-Cas provides resistance to phage and other MGEs by inserting phage-derived sequences into CRISPR loci on the host genome to allow sequence specific immunological memory against re-infection. Compared to the specific mechanism of CRISPR-Cas, phage resistance via surface modification provides general defense against a range of phage by physically modifying the cell surface to prevent phage infection. CRISPR-Cas and surface modification have been shown to be the most common mechanisms for rapid evolution of de novo phage resistance and therefore likely play important roles in shaping microbial communities. It has been suggested that we may be able to manipulate CRISPR-Cas evolution to our advantage, but very little research has been done investigating the evolutionary outcome of such manipulation. In this thesis I investigate the importance of different ecological drivers on when CRISPR-Cas is favoured over phage resistance via surface modification. I find that increasing CRISPR allele diversity within a host population increases phage immunity at the population level. However, increasing genetic diversity within the phage population increases selection for generalist phage defence via surface modification over specific CRISPR-Cas resistance. I also attempt to investigate the importance of cell-cell communication in the evolution of bacterial resistance; however these experiments were hampered by secondary effects of inhibiting cell-cell communication. These results are discussed in context with recent findings with the aim of expanding our knowledge of CRISPR-Cas evolution and ecology and suggesting where further research would be beneficial.