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This study analyzed the evolutionary dynamics of the insertion sequence IS6110 in 10,000 strains of Mycobacterium tuberculosis complex using a novel genomic tool. The researchers found that IS6110 copy numbers vary widely across strains (1 to over 30 copies), with insertion rates scaling linearly with copy number and showing elevated activity on terminal branches due to delayed purifying selection. Half of all independent insertion events concentrate in just 5% of genomic regions (hotspots), driven by both non-random insertion targeting a specific DNA motif and purifying selection against insertions in functionally important regions.
Why it matters
Understanding IS6110 dynamics is critical for tuberculosis epidemiology since this element is widely used for strain typing and tracking disease transmission. The findings reveal how transposable elements shape pathogen genome evolution and suggest that IS6110 distribution is constrained by the scarcity of genomic regions that are both mechanistically favorable for insertion and functionally tolerable for the bacterium.
⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Insertion sequences (IS) are the most common type of transposable element in prokaryotes and shape the structure of genomes through transposition and by providing a substrate for recombination. Despite the mutational impact of IS, the evolutionary dynamics of most elements in host species remain unknown. Here we study the dynamics of IS6110 in 10,000 strains of the Mycobacterium tuberculosis complex (MTBC). We developed a tool that allows the detection and comparison of IS insertions from short reads without using a reference genome. Using ancestral state reconstruction (ASR) on presence-absence patterns of IS6110, we describe the distribution of copy numbers (CNs) in the MTBC, infer birth rates of the element, and identify genomic regions with large numbers of parallel IS6110 insertions. Copy numbers in the MTBC range from 1 in some clades to more than 30 in strains of La3 (M. orygis). IS6110 birth rates scale approximately linearly with copy number and are elevated on terminal branches, consistent with the delayed action of purifying selection. A key characteristic of IS6110 is its occurrence in hotspots: the 5% most frequently targeted regions account for half of all independent insertion events. The motif 5′-TCTCAAAW-3′ is enriched around target sites and in hotspots, suggesting that the accumulation of insertions in these regions results through a combination of non-random insertion and purifying selection in other regions. To conclude the study, we propose a niche constraints model according to which the distribution of IS6110 in the MTBC is governed by the rarity of regions that have both suitable DNA properties and little functional value for the host.
Source: Evolutionary dynamics of the insertion sequence IS6110 in the Mycobacterium tuberculosis complex