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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
Persisting viral sequences shape microbial CRISPR-based immunity
PLoS Computational Biology, Volume 8, No. 4, Article e1002475, Year 2012
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Description
Well-studied innate immune systems exist throughout bacteria and archaea, but a more recently discovered genomic locus may offer prokaryotes surprising immunological adaptability. Mediated by a cassette-like genomic locus termed Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), the microbial adaptive immune system differs from its eukaryotic immune analogues by incorporating new immunities unidirectionally. CRISPR thus stores genomically recoverable timelines of virus-host coevolution in natural organisms refractory to laboratory cultivation. Here we combined a population genetic mathematical model of CRISPR-virus coevolution with six years of metagenomic sequencing to link the recoverable genomic dynamics of CRISPR loci to the unknown population dynamics of virus and host in natural communities. Metagenomic reconstructions in an acid-mine drainage system document CRISPR loci conserving ancestral immune elements to the base-pair across thousands of microbial generations. This 'trailer-end conservation' occurs despite rapid viral mutation and despite rapid prokaryotic genomic deletion. The trailer-ends of many reconstructed CRISPR loci are also largely identical across a population. 'Trailer-end clonality' occurs despite predictions of host immunological diversity due to negative frequency dependent selection (kill the winner dynamics). Statistical clustering and model simulations explain this lack of diversity by capturing rapid selective sweeps by highly immune CRISPR lineages. Potentially explaining 'trailer-end conservation,' we record the first example of a viral bloom overwhelming a CRISPR system. The polyclonal viruses bloom even though they share sequences previously targeted by host CRISPR loci. Simulations show how increasing random genomic deletions in CRISPR loci purges immunological controls on long-lived viral sequences, allowing polyclonal viruses to bloom and depressing host fitness. Our results thus link documented patterns of genomic conservation in CRISPR loci to an evolutionary advantage against persistent viruses. By maintaining old immunities, selection may be tuning CRISPR-mediated immunity against viruses reemerging from lysogeny or migration. © 2012 Weinberger et al.
Authors & Co-Authors
Sun, Christine L.
United States, Berkeley
University of California, Berkeley
Pluciński, Mateusz M.
United States, Berkeley
University of California, Berkeley
Denef, Vincent J.
United States, Berkeley
University of California, Berkeley
Thomas, Brian C.
United States, Berkeley
University of California, Berkeley
Barrangou, Rodolphe Lit Engl
Unknown Affiliation
Gilmore, Michael S.
United States, Boston
Harvard Medical School
United States, Cambridge
Harvard University
Getz, Wayne Marcus
United States, Berkeley
University of California, Berkeley
Banfield, Jillian F.
United States, Berkeley
University of California, Berkeley
Statistics
Citations: 105
Authors: 8
Affiliations: 4
Identifiers
Doi:
10.1371/journal.pcbi.1002475
ISSN:
1553734X
Research Areas
Cancer
Genetics And Genomics
Study Design
Cross Sectional Study