SpacerPlacer: ancestral reconstruction of CRISPR arrays reveals the evolutionary dynamics of spacer deletions.

Autor:	Fehrenbach A; Cluster of Excellence 'Controlling Microbes to Fight Infections', Mathematical and Computational Population Genetics, University of Tübingen, 72076 Tübingen, Germany.; Institute for Bioinformatics and Medical Informatics (IBMI), University of Tübingen, 72076 Tübingen, Germany., Mitrofanov A; Bioinformatics group, Department of Computer Science, University of Freiburg, 79085 Freiburg, Germany., Alkhnbashi OS; Center for Applied and Translational Genomics (CATG), Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU), Dubai Healthcare City, 505055 Dubai, United Arab Emirates.; College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU), Dubai Healthcare City, 505055 Dubai, United Arab Emirates., Backofen R; Bioinformatics group, Department of Computer Science, University of Freiburg, 79085 Freiburg, Germany.; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, 79085 Freiburg, Germany., Baumdicker F; Cluster of Excellence 'Controlling Microbes to Fight Infections', Mathematical and Computational Population Genetics, University of Tübingen, 72076 Tübingen, Germany.; Institute for Bioinformatics and Medical Informatics (IBMI), University of Tübingen, 72076 Tübingen, Germany.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2024 Oct 14; Vol. 52 (18), pp. 10862-10878.
DOI:	10.1093/nar/gkae772
Abstrakt:	Bacteria employ CRISPR-Cas systems for defense by integrating invader-derived sequences, termed spacers, into the CRISPR array, which constitutes an immunity memory. While spacer deletions occur randomly across the array, newly acquired spacers are predominantly integrated at the leader end. Consequently, spacer arrays can be used to derive the chronology of spacer insertions. Reconstruction of ancestral spacer acquisitions and deletions could help unravel the coevolution of phages and bacteria, the evolutionary dynamics in microbiomes, or track pathogens. However, standard reconstruction methods produce misleading results by overlooking insertion order and joint deletions of spacers. Here, we present SpacerPlacer, a maximum likelihood-based ancestral reconstruction approach for CRISPR array evolution. We used SpacerPlacer to reconstruct and investigate ancestral deletion events of 4565 CRISPR arrays, revealing that spacer deletions occur 374 times more frequently than mutations and are regularly deleted jointly, with an average of 2.7 spacers. Surprisingly, we observed a decrease in the spacer deletion frequency towards both ends of the reconstructed arrays. While the resulting trailer-end conservation is commonly observed, a reduced deletion frequency is now also detectable towards the variable leader end. Finally, our results point to the hypothesis that frequent loss of recently acquired spacers may provide a selective advantage. (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Databáze:	MEDLINE
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