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Phages are known to recombine with each other and have flexible and fluid genomes. We analyzed diversity within the clusters of the Acinetobacteriophage Database by organizing their genomes into pangenome graphs based on homologous phams (protein families).
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We then use these improved estimates of neutral mutation rates to look for regions with evidence that synonymous or non-coding mutations are under purifying selection. The majority of clear signals correspond to well known structures like the ORF1a/b frameshift and TRS. But there are two clear signals for which we could not find a clear explanation (in E, and at the M/ORF6 boundary).
[6/N]
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A simple linear model with genomic region, 5' and 3' neighborhood, and 2nd pairing explains between 15 and 60% of the fold-variation of the rates.
[5/N]
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We know that some rates, like C>T(U) are much higher than others, but even for the same mutation type, rates vary dramatically from site to site. A>T mutations are 2-3 fold more common after the start of Spike than before. C>T drops almost two-fold at the ORF1a/b boundary. The underlying mechanism is a mystery to us (we speculate a bit in the preprint).
[2/N]
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Within the syntenic core genome, linkage between SNPs decays rapidly with distance. LD approaches background levels after about 1000 bases. The background level itself is often set by population structure with little linkage within subgrou…
Using these cluster-wide pangenome graphs, we find a strongly conserved synteny of core phams. Accessory genome diversity is typically concentrated in well defined hotspots.
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Phages are known to recombine with each other and have flexible and fluid genomes. We analyzed diversity within the clusters of the Acinetobacteriophage Database by organizing their genomes into pangenome graphs based on homologous phams (…
We also use these mutation rate to provide (hopefully) more accurate estimates of amino acid substitutions.
https://neherlab.github.io/SARS2-mut-fitness-v2/
But mostly we are curious what explains these patterns of mutation rate variation…
We then use these improved estimates of neutral mutation rates to look for regions with evidence that synonymous or non-coding mutations are under purifying selection. The majority of clear signals correspond to well known structures like …
A simple linear model with genomic region, 5' and 3' neighborhood, and 2nd pairing explains between 15 and 60% of the fold-variation of the rates.
[5/N]
Base accessibility is like also the underlying reason for the dependence of mutation rates on RNA secondary structure, as described by Zach Hensel last year.
https://www.biorxiv.org/content/10.1101/2024.02.27.581995v2.abstract
[4/N]
Rates also depend on neighboring bases, sometimes by more than 10-fold. These neighbor-dependence is very strand symmetric for some mutations (e.g. T>G and A>C), but not for others.
A symmetry between strands would be expected for mutatio…
We know that some rates, like C>T(U) are much higher than others, but even for the same mutation type, rates vary dramatically from site to site. A>T mutations are 2-3 fold more common after the start of Spike than before. C>T drops almost…
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