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.
Highlights
To 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
Tuberculosis is caused by pathogens belonging to the Mycobacterium tuberculosis complex (MTBC) which consists of different species that are typical human pathogens (Micobacterium canettii, africanum, and tuberculosis), rodent ones (M. microti), or even Mycobacteria with a large host spectrum like bovis [1, 2]
Mycobacterium tuberculosis spreads throughout the human population since thousands of years, as the TB form that attacks bone and causes skeletal deformities can be still identified on individuals who died from it several thousands years ago, like ancient Egyptian mummies with apparent tubercular deformities
Summary
To 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. In 2015, more than 10 million people became ill with TB and approximately 2 millions died from the disease, almost exclusively in low and middle income countries It induces a major global health problem, since about one-third of the world’s population has latent TB. Tuberculosis is caused by pathogens belonging to the Mycobacterium tuberculosis complex (MTBC) which consists of different species that are typical human pathogens (Micobacterium canettii, africanum, and tuberculosis), rodent ones (M. microti), or even Mycobacteria with a large host spectrum like bovis [1, 2] Even if these organisms are genetically similar, they exhibit large differences with regard to epidemiology, pathogenicity, and host spectrum. Mycobacterium tuberculosis spreads throughout the human population since thousands of years, as the TB form that attacks bone and causes skeletal deformities can be still identified on individuals who died from it several thousands years ago, like ancient Egyptian mummies with apparent tubercular deformities
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
