CRISPR-Cas Inhibits Natural Transformation Through Altruistic Group Defense and Self-Sacrifice

CRISPR-Cas systems present an evolutionary tradeoff: does defense against phages and other parasitic DNA also prevent cells from acquiring potentially helpful new genes? Genomic analyses of this conundrum have arrived at often contradictory conclusions. Meanwhile, experimental studies have focused mainly on phages, conjugation, or artificial transformation, but less work has examined natural competence, a major driver of evolution and antibiotic resistance. Here, we use Acinetobacter baylyi , which combines high natural competence with a functional CRISPR-Cas system, to experimentally probe the interactions between CRISPR-Cas and natural competence. In these bacteria, the endogenous CRISPR array largely allows natural transformation by targeted DNA. However, CRISPR-Cas then kills the newly autoimmune cells in a form of programmed cell death. CRISPR-Cas often allows self-targeting cells to form colonies, albeit with fitness costs. Thus CRISPR-Cas appears to block natural transformation in a process more akin to altruistic group defense than an individual immune system. ### Competing Interest Statement J.H. is a co-founder and board member with equity in GenCirq Inc, which focuses on cancer therapeutics.