CRISPR-Cas spacer acquisition is a rare event in human gut microbiome

• Main Authors: Zhang, An-Ni, Gaston, Jeffry M., Cárdenas, Pablo, Zhao, Shijie, Gu, Xiaoqiong, Alm, Eric J.
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2025
• Subjects: Medicine, Health and Life Sciences; CRISPR-Cas systems; Human gut microbiome
• Online Access: https://hdl.handle.net/10356/182566
• Institution: Nanyang Technological University

Host-parasite relationships drive the evolution of both parties. In microbe-phage dynamics, CRISPR functions as an adaptive defense mechanism, updating immunity via spacer acquisition. Here, we investigated these interactions within the human gut microbiome, uncovering low frequencies of spacer acquisition at an average rate of one spacer every ∼2.9 point mutations using isolates’ whole genomes and ∼2.7 years using metagenome time series. We identified a highly prevalent CRISPR array in Bifidobacterium longum spreading via horizontal gene transfer (HGT), with six spacers found in various genomic regions in 15 persons from the United States and Europe. These spacers, targeting two prominent Bifidobacterium phages, comprised 76% of spacer occurrence of all spacers targeting these phages in all B. longum populations. This result suggests that HGT of an entire CRISPR-Cas system introduced three times more spacers than local CRISPR-Cas acquisition in B. longum. Overall, our findings identified key ecological and evolutionary factors in prokaryote adaptive immunity.