Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages

• DOI: 10.1186/s12864-016-2467-y
• Publication Date: 2016-02-28T23:33:53Z
• Authors: Jody E. Phelan; Francesc Coll; Indra Bergval; Richard M. Anthony; Rob Warren; Samantha L. Sampson; Nicolaas C. Gey v...; Judith R. Glynn; Amelia C. Crampin; Adriana Alves; Theolis Barbosa B...; Susana Campino; Keertan Dheda; Louis Grandjean; Rumina Hasan; Zahra Hasan; Anabela Miranda; David Moore; Stefan Panaiotov; Joao Perdigao; Isabel Portugal; Patricia Sheen; Erivelton de Oliv...; Elizabeth M. Stre...; Paul D. van Helden; Miguel Viveiros; Martin L. Hibberd; Arnab Pain; Ruth McNerney; Taane G. Clark
• Keywords: ppe gene; Epidemiology; genotype; major histocompatibility antigen; FOS: Health sciences; Gene; Epitopes; bacterial genome; Pathology; genetics; Phylogeny; Tuberculosis Lineage; Recombination, Genetic; epitope; genetic recombination; https://purl.org/pe-repo/ocde/ford#1.06.07; Bacterial; Life Sciences; Genomics; 3. Good health; Multigene Family; sequence alignment; Medicine; 570; Genotype; Evolution; DNA sequence; 610; gene sequence; Microbiology; Article; Variable Selective Pressure; Diagnosis, Treatment, and Epidemiology of Nontuberculous Mycobacterial Diseases; Evolution, Molecular; 03 medical and health sciences; Genetic; Health Sciences; genomics; Genetics; Tuberculosis; procedures; Polymorphism; Molecular Biology; Biology; molecular evolution; bacterium isolate; Molecular; DNA; Proline-glutamate (PE and PPE); bacterial DNA; Genomics/methods; genetic selection; Genes; FOS: Biological sciences; Mutation; Gene expression; mutation; 0301 basic medicine; protein binding; phylogeny; Vaccines -- Design; single nucleotide polymorphism; vaccine; genetic variability; proline; Ribosome Structure and Translation Mechanisms; Genome; Single Nucleotide; Proline Glutamate; pe gene; DNA, Bacterial/genetics; Infectious Diseases; Mycobacterium tuberculosis/genetics; glutamic acid; bacterial gene; Biotechnology; Research Article; DNA, Bacterial; Polymorphism, Single Nucleotide; Mycobacterium; Biochemistry, Genetics and Molecular Biology; Major Histocompatibility Complex Molecule; Genetic variation; Selection, Genetic; multigene family; Mycobacterium tuberculosis -- Genetic aspects; nonhuman; Mycobacterium tuberculosis -- Vaccination; DNA microarray; Mycobacterium Tuberculosis Complex; Bacteriology; Sequence Analysis, DNA; Mycobacterium tuberculosis; gene structure; Recombination; Genes, Bacterial; Genome, Bacterial

Approximately 10% of the Mycobacterium tuberculosis genome is made up two families genes that are poorly characterized due to their high GC content and highly repetitive nature. The PE PPE typified by conserved N-terminal domains incorporate proline-glutamate (PE) proline-proline-glutamate (PPE) signature motifs. They hypothesised be important virulence factors involved with host-pathogen interactions, but genetic variability complexity analysis means they typically disregarded in studies.To elucidate structure these genes, 518 genomes from a diverse international collection clinical isolates were de novo assembled. A further 21 reference M. complex long read sequence data used validate approach. SNP revealed variation majority 168 pe/ppe studied was consistent lineage. Several recombination hotspots identified, notably pe_pgrs3 pe_pgrs17. Evidence positive selection 65 including epitopes potentially binding major histocompatibility molecules.This, first comprehensive study pe ppe provides insight into diversity has significant implications for vaccine development.