title: Deciphering the recent phylogenetic expansion of the originally deeply rooted Mycobacterium tuberculosis lineage 7.
abstract: A deeply rooted phylogenetic lineage of Mycobacterium tuberculosis (M. tuberculosis) termed lineage 7 was discovered in Ethiopia. Whole genome sequencing of 30 lineage 7 strains from patients in Ethiopia was performed. Intra-lineage genome variation was defined and unique characteristics identified with a focus on genes involved in DNA repair, recombination and replication (3R genes).
  
  
  
  More than 800 mutations specific to M. tuberculosis lineage 7 strains were identified. The proportion of non-synonymous single nucleotide polymorphisms (nsSNPs) in 3R genes was higher after the recent expansion of M. tuberculosis lineage 7 strain started. The proportion of nsSNPs in genes involved in inorganic ion transport and metabolism was significantly higher before the expansion began. A total of 22346 bp deletions were observed. Lineage 7 strains also exhibited a high number of mutations in genes involved in carbohydrate transport and metabolism, transcription, energy production and conversion.
  
  
  
  We have identified unique genomic signatures of the lineage 7 strains. The high frequency of nsSNP in 3R genes after the phylogenetic expansion may have contributed to recent variability and adaptation. The abundance of mutations in genes involved in inorganic ion transport and metabolism before the expansion period may indicate an adaptive response of lineage 7 strains to enable survival, potentially under environmental stress exposure. As lineage 7 strains originally were phylogenetically deeply rooted, this may indicate fundamental adaptive genomic pathways affecting the fitness of M. tuberculosis as a species.
authors.affiliation: Department of Microbiology, Oslo University Hospital, PO Box 4950, NO-0424, Oslo, Nydalen, Norway. s.a.yimer@medisin.uio.no.|Faculty of Medicine, University of Oslo, PO Box 1171, Blindern, 0318, Oslo, Norway. s.a.yimer@medisin.uio.no.
authors.forename: Solomon A
authors.initials: SA
authors.lastname: Yimer
authors.affiliation: Department of Microbiology, Oslo University Hospital, PO Box 4950, NO-0424, Oslo, Nydalen, Norway.
authors.forename: Amine
authors.initials: A
authors.lastname: Namouchi
authors.affiliation: Uni Research Environment, Centre for Applied Biotechnology, PO Box 7803, N-5020, Bergen, Norway.
authors.forename: Ephrem Debebe
authors.initials: ED
authors.lastname: Zegeye
authors.affiliation: Infection Control and Environmental Health, Norwegian Institute of Public Health, PO Box 4404, 0403, Oslo, Nydalen, Norway.
authors.forename: Carol
authors.initials: C
authors.lastname: Holm-Hansen
authors.affiliation: Infection Control and Environmental Health, Norwegian Institute of Public Health, PO Box 4404, 0403, Oslo, Nydalen, Norway.
authors.forename: Gunnstein
authors.initials: G
authors.lastname: Norheim
authors.affiliation: Armauer Hansen Research Institute, Jimma Road, PO Box 1005, Addis Ababa, Ethiopia.
authors.forename: Markos
authors.initials: M
authors.lastname: Abebe
authors.affiliation: Armauer Hansen Research Institute, Jimma Road, PO Box 1005, Addis Ababa, Ethiopia.
authors.forename: Abraham
authors.initials: A
authors.lastname: Aseffa
authors.affiliation: Department of Microbiology, Oslo University Hospital, PO Box 4950, NO-0424, Oslo, Nydalen, Norway.|Faculty of Medicine, University of Oslo, PO Box 1171, Blindern, 0318, Oslo, Norway.
authors.forename: Tone
authors.initials: T
authors.lastname: Tønjum
mesh_terms: D005075:Biological Evolution; D005002:Ethiopia; D016680:Genome, Bacterial; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000145:classification* / Q000235:genetics* / Q000378:metabolism; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D017384:Sequence Deletion; D014376:Tuberculosis / Q000382:microbiology
keywords: 3R genes; Amhara Region; Ethiopia; Lineage 7; Mutations; Mycobacterium tuberculosis; Single nucleotide polymorphism; Whole genome sequencing