CRISPR arrays store "immune memories" of past invaders as spacers. But these memories aren’t permanent— frequent spacer deletions reshape the array. We investigated the spacer deletion dynamics with our new reconstruction tool and learned a lot... 🧵 https://t.co/0pHz1MR412
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Spacer deletions in CRISPR arrays follow fascinating patterns. Using our tool SpacerPlacer, we found that deletion events are 374x more frequent than single-nucleotide mutations, making immunity loss by spacer loss much more likely than by mutations.
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Interestingly, besides the loss of a single spacer, deletions occur often in blocks, involving an average of 2.7 spacers per event. This block deletion aligns with theories of replication slippage, where nearby repeats misalign, leading to multiple spacer deletions.
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Consistent with this mechanism, we observe a “boundary effect”: Spacer deletions are less frequent near the leader and trailer ends of the array, potentially due to fewer neighboring repeats for alignment, while the middle of the array sees the most deletions.
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Besides the boundary effect, we observe no change of deletion frequencies along arrays. They evolve surely non-neutrally, but our results hint at either weak selection pressures to delete specific spacers or an equally strong selection along the array to maintain spacers. But,...
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The spacer deletions at the very first and last positions of CRISPR arrays deviate from a symmetric boundary effect. The reconstructed deletion rate is higher at the first positions compared to the losses at the last positions. This might have multiple reasons ...
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CRISPR spacer deletions may be more common at the leader due to a) mutations of the last repeat b) recently acquired spacers lacking a long-term benefit c) benefits of changing the spacers at the first most expressed positions d) (reconstruction errors) e) all of the above
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Finally, across multiple CRISPR-Cas types and genera, we found no significant difference in deletion rates or lengths, suggesting that spacer deletions are likely not modulated by Cas proteins.
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