|PATANE, JOSE - Universidade De Sao Paulo|
|MARTINS, JOAQUIM - Universidade De Sao Paulo|
|CASTELAO, ANA - Universidade Federal De Mato Grosso|
|NISHIBE, CHRISTIANE - Universidade Federal De Mato Grosso|
|MONTERA, LUCIANA - Universidade Federal De Mato Grosso|
|BIGI, FABIANA - Instituto Nacional De Tecnologia Agropecuaria|
|ZUMARRAGO, MARTIN - Instituto Nacional De Tecnologia Agropecuaria|
|CATALDI, ANGEL - Instituto Nacional De Tecnologia Agropecuaria|
|JUNIOR, ANTONIO - Ministerio De Agricultura|
|ROXO, ELIANA - Instituto Biologicio - Brazil|
|OSORIO, ANA - Universidade Federal De Mato Grosso|
|JORGE, KLAUDIA - Universidade Federal De Mato Grosso|
|DE ALMEIA, FRANCO - Universidade Federal De Mato Grosso|
|ARAUJO, FLABIO - Embrapa|
|SETUBAL, JOAO - Universidade De Sao Paulo|
Submitted to: Genome Biology and Evolution
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/8/2017
Publication Date: 3/1/2017
Citation: Patane, J.S., Martins, J., Castelao, A.B., Nishibe, C., Montera, L., Bigi, F., Zumarrago, M.J., Cataldi, A.A., Junior, A.F., Roxo, E., Osorio, A.L., Jorge, K.S., Thacker, T.C., De Almeia, F., Araujo, F.R., Setubal, J.C. 2017. Patterns and processes of Mycobacterium bovis evolution revealed by phylogenomic analyses. Genome Biology and Evolution. doi: 10.1093/gbe/evx022.
Interpretive Summary: Mycobacterium bovis is an important animal pathogen worldwide that infects wild and domesticated livestock as well as humans. A comparison of five complete M. bovis genomes from UK, South Korea, Brazil and USA revealed four novel large structural variations. An improved method of building an evolutionary tree suggests that changes in genes contributing to lipid transport and metabolism, cell growth, motility, and virulence play a significant role in evolution of these strains. Analysis of strains from the US did not cluster by state, except for areas with localized infections. When bacteria were isolated from wildlife and cattle from the same area they were monophyletic or in other words the same strain. This data will be of interest to livestock producers, regulatory officials and scientists working on tuberculosis research.
Technical Abstract: Mycobacterium bovis is an important animal pathogen worldwide that parasitizes wild and domesticated vertebrate livestock as well as humans. A comparison of the five M. bovis complete genomes from UK, South Korea, Brazil and USA revealed four novel large-scale structural variations of at least 2,000 bp. A comparative phylogenomic study including 2,483 core genes of 38 taxa from eight countries showed conflicting phylogenetic signal among sites. By minimizing this effect, we obtained a tree that better agrees with sampling locality. Results supported a relatively basal position of African strains (all isolated from Homo sapiens), confirming that Africa was an important region for early diversification and that humans were one of the earliest hosts. Selection analyses revealed that functional categories such as "Lipid transport and metabolism", "Cell cycle control, cell division, chromosome partitioning" and "Cell motility" were significant for the evolution of the group, besides other categories previously described, showing importance of genes associated with virulence and cholesterol metabolism in the evolution of M. bovis. PE/PPE genes, many of which are known to be associated with virulence, were major targets for large-scale polymorphisms, homologous recombination, and positive selection, evincing for the first time a plethora of evolutionary forces possibly contributing to differential adaptability in M. bovis. The origin of M. bovis was estimated at 800 - 4,630 years ago (ya). USA strains started to diverge 274 - 2,638 ya. By further analyzing the largest set of USA genomes to date (76 in total), obtained from 14 host species, we detected population expansion starting around 200 ya, correlating with increase in importation of cattle from other countries. USA genomes did not cluster by state, except for localized MI, HI, NY, MN, and CO clades, suggesting fast spread of bovine tuberculosis. For MI, NY, and MN, samples from different hosts formed monophyletic clades by state, corroborating previous assertions of native wildlife species acting as local reservoirs re-contaminating cattle (or other species in the case of NY) on different occasions. Hosts did not form monophyletic clades either, suggesting ongoing re-infections across species. Some unrelated lineages had much faster evolutionary rates, which could be due to recent selective sweeps. Overall, these results evince the possibility of new bovine tuberculosis outbreaks in the future.