Dataset Information

Recombination Signal in Mycobacterium tuberculosis Stems from Reference-guided Assemblies and Alignment Artefacts.

ABSTRACT: DNA acquisition via genetic recombination is considered advantageous as it has the potential to bring together beneficial mutations that emerge independently within a population. Furthermore, recombination is considered to contribute to the maintenance of genome stability by purging slightly deleterious mutations. The prevalence of recombination differs among prokaryotic species and depends on the accessibility of DNA transfer mechanisms. An exceptional example is the human pathogen Mycobacterium tuberculosis (MTB) where no clear transfer mechanisms have been so far characterized and the presence of recombination is questioned. Here, we analyze completely assembled MTB genomes in search for evidence of recombination. We find that putative recombination events are enriched in strains reconstructed by reference-guided assembly and in regions with unreliable alignments. In addition, assembly and alignment artefacts introduce phylogenetic signals that are conflicting the established MTB phylogeny. Our results reveal that the so far reported recombination events in MTB are likely to stem from methodological artefacts. We conclude that no reliable signal of recombination is observed in the currently available MTB genomes. Moreover, our study demonstrates the limitations of reference-guided genome assembly for phylogenetic reconstructions. Rigorously de novo assembled genomes of high quality are mandatory in order to distinguish true evolutionary signal from noise, in particular for low diversity species such as MTB.

SUBMITTER: Godfroid M

PROVIDER: S-EPMC6086087 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Recombination Signal in Mycobacterium tuberculosis Stems from Reference-guided Assemblies and Alignment Artefacts.

Godfroid Maxime M Dagan Tal T Kupczok Anne A

Genome biology and evolution 20180801 8

DNA acquisition via genetic recombination is considered advantageous as it has the potential to bring together beneficial mutations that emerge independently within a population. Furthermore, recombination is considered to contribute to the maintenance of genome stability by purging slightly deleterious mutations. The prevalence of recombination differs among prokaryotic species and depends on the accessibility of DNA transfer mechanisms. An exceptional example is the human pathogen Mycobacteriu ...[more]

PMID: 30010866

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Project description:Mycobacterium tuberculosis is a strict aerobe capable of prolonged survival in the absence of oxygen. We investigated the ability of anaerobic M. tuberculosis to counter challenges to internal pH homeostasis in the absence of aerobic respiration, the primary mechanism of proton efflux for aerobic bacilli. Anaerobic M. tuberculosis populations were markedly impaired for survival under a mildly acidic pH relative to standard culture conditions. An acidic environmental pH greatly increased the susceptibilities of anaerobic bacilli to the collapse of the proton motive force by protonophores, to antimicrobial compounds that target entry into the electron transport system, and to small organic acids with uncoupling activity. However, anaerobic bacilli exhibited high tolerance against these challenges at a near-neutral pH. At a slightly alkaline pH, which was near the optimum intracellular pH, the addition of protonophores even improved the long-term survival of bacilli. Although anaerobic M. tuberculosis bacilli under acidic conditions maintained 40% lower ATP levels than those of bacilli under standard culture conditions, ATP loss alone could not explain the drop in viability. Protonophores decreased ATP levels by more than 90% regardless of the extracellular pH but were bactericidal only under acidic conditions, indicating that anaerobic bacilli could survive an extreme ATP loss provided that the external pH was within viable intracellular parameters. Acidic conditions drastically decreased the anaerobic survival of a DosR mutant, while an alkaline environment improved the survival of the DosR mutant. Together, these findings indicate that intracellular acidification is a primary challenge for the survival of anaerobic M. tuberculosis and that the DosR regulon plays a critical role in sustaining internal pH homeostasis.IMPORTANCE During infection, M. tuberculosis bacilli are prevalent in environments largely devoid of oxygen, yet the factors that influence the survival of these severely growth-limited and metabolically limited bacilli remain poorly understood. We determined how anaerobic bacilli respond to fluctuations in environmental pH and observed that these bacilli were highly susceptible to stresses that promoted internal acidic stress, whereas conditions that promoted an alkaline internal pH promoted long-term survival even during severe ATP depletion. The DosR regulon, a major regulator of general hypoxic stress, played an important role in maintaining internal pH homeostasis under anaerobic conditions. Together, these findings indicate that in the absence of aerobic respiration, protection from internal acidification is crucial for long-term M. tuberculosis survival.

Dataset Information

Recombination Signal in Mycobacterium tuberculosis Stems from Reference-guided Assemblies and Alignment Artefacts.

Publications

Recombination Signal in Mycobacterium tuberculosis Stems from Reference-guided Assemblies and Alignment Artefacts.

Similar Datasets

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