On the reconstruction of the ancestral bacterial genomes in genus Mycobacterium and Brucella

Abstract

BackgroundTo reconstruct the evolution history of DNA sequences, novel models of increasing complexity regarding the number of free parameters taken into account in the sequence evolution, as well as faster and more accurate algorithms, and statistical and computational methods, are needed. More particularly, as the principal forces that have led to major structural changes are genome rearrangements (such as translocations, fusions, and so on), understanding their underlying mechanisms, among other things via the ancestral genome reconstruction, are essential. In this problem, since finding the ancestral genomes that minimize the number of rearrangements in a phylogenetic tree is known to be NP-hard for three or more genomes, heuristics are commonly chosen to obtain approximations of the exact solution. The aim of this work is to show that another path is possible.ResultsVarious algorithms and software already deal with the difficult nature of the problem of reconstruction of the ancestral genome, but they do not function with precision, in particular when indels or single nucleotide polymorphisms fall into repeated sequences. In this article, and despite the theoretical NP-hardness of the ancestral reconstruction problem, we show that an exact solution can be found in practice in various cases, encompassing organelles and some bacteria. A practical example proves that an accurate reconstruction, which also allows to highlight homoplasic events, can be obtained. This is illustrated by the reconstruction of ancestral genomes of two bacterial pathogens, belonging in Mycobacterium and Brucella genera.ConclusionsBy putting together automatically reconstructed ancestral regions with handmade ones for problematic cases, we show that an accurate reconstruction of ancestors of the Brucella genus and of the Mycobacterium tuberculosis complex is possible. By doing so, we are able to investigate the evolutionary history of each pathogen by computing their common ancestors. They can be investigated extensively, by studying the gene content evolution over time, the resistance acquisition, and the impacts of mobile elements on genome plasticity.

CRISPRbuilder-TB: “CRISPR-builder for tuberculosis”. Exhaustive reconstruction of the CRISPR locus in mycobacterium tuberculosis complex using SRA

“…In this article, we present a new general procedure termed ‘CRISPRbuilder-TB’ to reconstruct Mycobacterium tuberculosis CRISPR-Cas loci from short reads under a semi-automatized process. CRISPRbuilder-TB is inspired by previous developments [ 24 , 25 ] and particularizes the De Bruijn approach to the specific case of reconstructing CRISPR loci based on SRA, with the condition that its standard DR sequence is known. Applied on TB SRA without any genome assembly step, CRISPRbuilder-TB proved reliable and robust with reads of more than 75bp.…”

Exhaustive reconstruction of the CRISPR locus inMycobacterium tuberculosiscomplex using short reads

“…It is reliable and robust provided that the reads have sufficient coverage and sizes long enough to span more than one DR. This tool, based on the analyses carried out in [17, 18] particularizes the De Bruijn approach to the specific case of the CRISPR locus and is the main contribution of this article. We show its usefulness both by showing that it can reconstruct CRISPR of reliable reference genomes, and by presenting that mean quality of CRISPR-Cas reconstruction is poor in other assembled genomes available in the public databases.…”

Investigating the Diversity of Tuberculosis Spoligotypes with Dimensionality Reduction and Graph Theory

“…We also find, in the upper right part, lineages 2 to 4, and in the lower left part, lineages 1, 5, 6 and animal, and we know that these two subgroups are phylogenetically separated. The clusters of lineages 1 to 4 extend to the center of the cloud, arguing for a common origin of the tuberculosis complex, whose common ancestor could be M. canettii [ 20 ].…”