@fbaumdicker
Franz Baumdicker
1 year
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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@fbaumdicker
Franz Baumdicker
1 year
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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@fbaumdicker
Franz Baumdicker
1 year
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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@fbaumdicker
Franz Baumdicker
1 year
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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@fbaumdicker
Franz Baumdicker
1 year
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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@fbaumdicker
Franz Baumdicker
1 year
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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@fbaumdicker
Franz Baumdicker
1 year
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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@fbaumdicker
Franz Baumdicker
1 year
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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@fbaumdicker
Franz Baumdicker
1 year
It is crucial to use reconstructed arrays to see these deletion patterns, as the position of spacers shifts toward the trailer end over time. I will post more details about our reconstruction tool SpacerPlacer later. But you can find the tool here:
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@ZaminIqbal
Zamin Iqbal
1 year
@fbaumdicker Fantastic, super interesting!
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