AbstractThe CRISPR-Cas systems are important prokaryotic adaptive immune systems and effectively record the arms-race between bacteria and invading mobile elements in their CRISPR arrays. Using data from culture-based population genomics and metagenomics, we investigated the CRISPR-Cas systems associated with Bacteriodes fragilis, an important gut bacterium, and studied their diversity and dynamics. We analyzed genomes of 601 B. fragilis isolates derived from 12 healthy individuals, among which include time-series isolates from 6 individuals. In addition, we analyzed 222 reference B. fragilis genomes. Three different types of CRISPR-Cas systems (Type I-B, II-C and III-B) were found in analyzed B. fragilis genomes, with Type III-B being the most prevalent whereas the Type II-C being the most dynamic with varying arrays among isolates. Our graph-based summary and visualization of CRISPR arrays provided a holistic view of the organization and the composition of the CRISPR spacers. We observed insertions of different new spacers at the leader ends of the CRISPR arrays of Type II-C CRISPR-Cas systems in different B. fragilis sub-populations in one individual, an example of B. fragilis’ adaptation and parallel evolution within individual microbiomes. A network of B. fragilis and its predicted invaders also revealed microdynamics of B. fragilis CRISPR array, with hairball-like structures representing spacers with multi-target capabilities and network modules revealing the collective targeting of selected mobile elements by many spacers. This work demonstrates the power of using culture-based population genomics to reveal the activities and evolution of the CRISPR-Cas systems of the important gut bacterium B. fragilis in human population.
Human population genomics approach in food metabolism