title: Genomic analyses of the ancestral Manila family of Mycobacterium tuberculosis.
abstract: With its airborne transmission and prolonged latency period, Mycobacterium tuberculosis spreads worldwide as one of the most successful bacterial pathogens and continues to kill millions of people every year. M. tuberculosis lineage 1 is inferred to originate ancestrally based on the presence of the 52-bp TbD1 sequence and analysis of single nucleotide polymorphisms. Previously, we briefly reported the complete genome sequencing of M. tuberculosis strains 96121 and 96075, which belong to the ancient Manila family and modern Beijing family respectively. Here we present the comprehensive genomic analyses of the Manila family in lineage 1 compared to complete genomes in lineages 2-4. Principal component analysis of the presence and absence of CRISPR spacers suggests that Manila isolate 96121 is distinctly distant from lineages 2-4. We further identify a truncated whiB5 gene and a putative operon consisting of genes encoding a putative serine/threonine kinase PknH and a putative ABC transporter, which are only found in the genomes of Manila family isolates. Six single nucleotide polymorphisms are uniquely conserved in 38 Manila strains. Moreover, when compared to M. tuberculosis H37Rv, 59 proteins are under positive selection in Manila family isolate 96121 but not in Beijing family isolate 96075. The unique features further serve as biomarkers for Manila strains and may shed light on the limited transmission of this ancestral lineage outside of its Filipino host population.
authors.affiliation: Advanced Studies in Genomics, Proteomics and Bioinformatics, University of Hawaii, Honolulu, Hawaii, United States of America.
authors.forename: Xuehua
authors.identifier: http://orcid.org/0000-0002-6367-848X
authors.initials: X
authors.lastname: Wan
authors.affiliation: Department of Microbiology, University of Hawaii, Honolulu, Hawaii, United States of America.
authors.forename: Kent
authors.initials: K
authors.lastname: Koster
authors.affiliation: Department of Microbiology, University of Hawaii, Honolulu, Hawaii, United States of America.
authors.forename: Lishi
authors.initials: L
authors.lastname: Qian
authors.affiliation: Microbial Diseases Laboratory, California Department of Public Health, Richmond, California, United States of America.
authors.forename: Edward
authors.initials: E
authors.lastname: Desmond
authors.affiliation: TB Control Program, Hawaii State Department of Health, Honolulu, Hawaii, United States of America.
authors.forename: Richard
authors.initials: R
authors.lastname: Brostrom
authors.affiliation: Advanced Studies in Genomics, Proteomics and Bioinformatics, University of Hawaii, Honolulu, Hawaii, United States of America.
authors.forename: Shaobin
authors.initials: S
authors.lastname: Hou
authors.affiliation: Department of Microbiology, University of Hawaii, Honolulu, Hawaii, United States of America.
authors.forename: James T
authors.initials: JT
authors.lastname: Douglas
mesh_terms: D064112:Clustered Regularly Interspaced Short Palindromic Repeats; D019143:Evolution, Molecular; D005260:Female; D005798:Genes, Bacterial; D016678:Genome; D006801:Humans; D008849:Micronesia; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000302:isolation & purification; D010679:Philippines; D020641:Polymorphism, Single Nucleotide; D025341:Principal Component Analysis; D017421:Sequence Analysis