Abstract
Mycobacterium is a genus of bacteria with over a hundred non-pathogenic and pathogenic species, best recognized for certain members known to cause diseases such as tuberculosis and leprosy. Two novel protein families important in the pathogenesis of Mycobacterium species are the PE and PPE families. These two protein families affect the antigenic profiles, disturbing host immunity. To better understand the origin and evolution of these gene families and the differences in their composition between pathogenic and non-pathogenic strains, several bioinformatic analyses were conducted both among Mycobacterium and closely related species that contain PE35 and PPE68 gene homologs. The methods included protein homology searches (BLASTP), horizontal gene transfer analysis (IslandViewer), phylogenetic analysis, gene cluster analysis and structural and functional constraints. Results revealed that PE and PPE gene homologs were not only limited to Mycobacterium, but also existed in three other non-mycobacterial genera, Rhodococcus, Tsukamurella and Segniliparus, and were possibly initially acquired from non-mycobacterial microorganisms by multiple horizontal gene transfers. Results also demonstrated that PE and PPE genes were more diverse and more rapidly evolving in pathogenic Mycobacterium as compared with non-pathogenic Mycobacterium and other non-mycobacterial species. These findings possibly shed light on the diverse functions and origins of the PE/PPE proteins among these organisms.
Highlights
Mycobacteria are a genus of acid-fast bacteria with over a hundred non-pathogenic and pathogenic species, bestHow to cite this paper: Bavishi, A., Lin, L., Choudhary, M. and Primm, T.P. (2014) Evolution of PE35 and PPE68 Gene Families in Mycobacterium: Roles of Horizontal Gene Transfer and Evolutionary Constraints
The reference PPE68 and PE35 proteins were selected from Mycobacterium tuberculosis CDC1551 (100% identical in H37Rv) and blasted against fully sequenced Mycobacterium genomes found in the National Center for Biotechnology Information (NCBI) database
The results showed that pathogenic mycobacteria had higher copy numbers of PPE genes as compared to nonpathogenic, again, with the exclusion of M. leprae
Summary
Mycobacteria are a genus of acid-fast bacteria with over a hundred non-pathogenic and pathogenic species, bestHow to cite this paper: Bavishi, A., Lin, L., Choudhary, M. and Primm, T.P. (2014) Evolution of PE35 and PPE68 Gene Families in Mycobacterium: Roles of Horizontal Gene Transfer and Evolutionary Constraints. Pathogenic strains generally grow slowly, forming colonies on solid media in several weeks to months, while environmental species are non-pathogenic and grow rapidly within a week [3] [4]. Pathogenicity is defined as the ability of a microorganism to cause disease that is harmful to the host. The genome of M. tuberculosis strain H37Rv is annotated with 99 and 69 PE and PPE proteins, respectively. Members of the PE protein family have conserved ~110 amino acid N-terminal domains with the proline-glutamic acid motif at positions 8 - 9 [5] [7] [8]. Members of the PPE family have longer ~180 amino acid conserved N-terminal domains with the proline-proline-glutamic acid motif at positions 7 - 9 [5] [8]. Compared with the conserved N-terminal domains, the C-terminal domains of both PE and PPE vary in sequence and length, often containing repetitive regions
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