Marco MolariJul 12, 2024
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Core-genome synteny, i.e. the order of core genes, has been shown to be strongly conserved across large evolutionary distances. But what happens on short timescales? Using the graph we can survey all possible changes of synteny in the dataset. Out of 222 isolates, we find only 26 with any change in synteny. Most of these changes are inversions, often around the origin or terminus of replication.
Show threadMarco MolariJul 12, 2024
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This suggests that changes in synteny are relatively frequent, occurring at a rough rate of one every ~250 clonally-inherited mutations on the (filtered) core-genome. However, the fact that synteny is largely conserved across big evolutionary distances, and the fact that many of these changes happen on terminal branches of the tree, indicate that these changes are likely removed by purifying selection.
Show threadMarco MolariJul 12, 2024
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Next we investigate the structural diversity in the accessory genome. The fact that the order of core-genes is mostly conserved provides a well-defined frame of reference in which to study accessory variation. We look at the local graph between two adjacent core blocks, that we call a junction graph. In this graph the diversity can be quantified in terms of number of distinct paths and total accessory sequence content.
Show threadMarco Molari
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If we scatter-plot these two quantities for all of the 519 junctions in the dataset, we find that the majority of junctions are binary, i.e. they contain only two possible distinct paths, of which one is often empty. Their length distribution is bimodal, with a peak around 1kbp and another around 30-40 kbp. On the other end of the spectrum we find hotspots, regions with tens to hundreds of different distinct paths, and a total accessory genome content of tens to hundreds of kbp in length.
Jul 12, 2024 at 8:16amWeb
Show threadMarco MolariJul 12, 2024
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By looking at the content of the junctions, we find that the two peaks in binary junctions are explained by the movement of insertion sequences and prophages respectively, while hotspots are very flexible regions, rich in mobile genetic elements and defense systems.
Show threadMarco MolariJul 12, 2024
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For binary junctions we can go even further: depending on their content and pattern of variation along the tree, they can be associated with gain or loss events.
In particular singleton junctions correspond to events on terminal branches of the tree, while non-singleton junctions can in principle be associated also to events on internal branches.
Show threadMarco MolariJul 12, 2024
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In binary junctions the vast majority of events are gains, often corresponding to an insertion sequence (IS) or prophage integrating in an otherwise conserved region of the genome. This corresponds to a rough rate of one of these events every 20 mutations on the (recombination-filtered) core-genome.
Show threadMarco MolariJul 12, 2024
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Most of the IS integrations disrupt genes, and such structural gains would be interpreted as loss events in gene-based analyses. However, this happens less than expected by chance given the high fraction of coding sequence in these genomes, indicating that roughly 2/3 of these integrations have already been removed by purifying selection.
Show threadMarco MolariJul 12, 2024
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To explain the total structural diversity of the dataset, more than 2000 distinct structural variations must have happened in its short evolutionary history, corresponding to an average rate of one every 3 mutations on the (recombination-filtered) core-genome. This is a remarkably high rate! We are curious to check in follow-up works whether these rates and patterns are specific to ST131, or are more general and can be found in other sequence types or even microbial species.
Show threadPeter van Heusden (he/him) 🗿Jan 6, 2025
@mrcmlr I'm fascinated whether operons have an impact on placement of hotspots etc?