title: Identification of a Non-Pentapeptide Region Associated with Rapid Mycobacterial Evolution.
abstract: A large portion of the coding capacity of Mycobacterium tuberculosis is devoted to the production of proteins containing several copies of the pentapeptide-2 repeat, namely the PE/PPE_MPTR proteins. Protein domain repeats have a variety of binding properties and are involved in protein-protein interactions as well as binding to other ligands such as DNA and RNA. They are not as common in prokaryotes, compared to eukaryotes, but the enrichment of pentapeptide-2 repeats in Mycobacteria constitutes an exception to that rule. The genes encoding the PE/PPE_MPTR proteins have undergone many rearrangements and here we have identified the expansion patterns across the Mycobacteria. We have performed a reclassification of the PE/PPE_MPTR proteins using cohesive regions rather than sparse domain architectures. It is clear that these proteins have undergone large insertions of several pentapeptide-2 domains appearing adjacent to one another in a repetitive pattern. Further, we have identified a non-pentapeptide motif associated with rapid mycobacterial evolution. The sequence composition of this region suggests a different structure compared to pentapeptide-2 repeats. By studying the evolution of the PE/PPE_MPTR proteins, we have distinguished features pertaining to tuberculosis-inducing species. Further studies of the non-pentapeptide region associated with repeat expansions promises to shed light on the pathogenicity of Mycobacterium tuberculosis.
authors.affiliation: Department of Biochemistry and Biophysics, Science for Life Laboratory, Stockholm University, SE-12 171 Solna, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Warholm
authors.affiliation: Department of Biochemistry and Biophysics, Bioinformatics Infrastructure for Life Sciences, Science for Life Laboratory, Stockholm University, SE-12 171 Solna, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Light
mesh_terms: D021901:DNA, Intergenic / Q000235:genetics; D019143:Evolution, Molecular; D005798:Genes, Bacterial / Q000235:genetics; D018895:Microsatellite Repeats / Q000235:genetics; D009161:Mycobacterium / Q000235:genetics; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D010802:Phylogeny; D000072417:Protein Domains / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid
chemical_list: D021901:DNA, Intergenic