The recombination-cold region as an epidemiological marker of recombinogenic opportunistic pathogen Mycobacterium avium

Hirokazu Yano, Haruo Suzuki, Fumito Maruyama, Tomotada Iwamoto

Research output: Contribution to journalArticle

Abstract

Background: The rapid identification of lineage remains a challenge in the genotyping of clinical isolates of recombinogenic pathogens. The chromosome of Mycobacterium avium subsp. hominissuis (MAH), an agent of Mycobacterium avium complex (MAC) lung disease, is often mosaic and is composed of chromosomal segments originating from different lineages. This makes it difficult to infer the MAH lineage in a simple experimental set-up. To overcome this difficulty, we sought to identify chromosomal marker genes containing lineage-specific alleles by genome data mining. Results: We conducted genetic population structure analysis, phylogenetic analysis, and a survey of historical recombination using data from 125 global MAH isolates. Six MAH lineages (EA1, EA2, SC1, SC2, SC3, and SC4) were identified in the current dataset. One P-450 gene (locus-tag MAH-0788/MAV-0940) in the recombination-cold region was found to have multiple alleles that could discriminate five lineages. By combining the information about allele type from one additional gene, the six MAH lineages as well as other M. avium subspecies were distinguishable. A recombination-cold region of 116 kb contains an insertion hotspot and is flanked by a mammalian cell-entry protein operon where allelic variants have previously been reported to occur. Hence, we speculate that the acquisition of lineage-or strain-specific insertions has introduced homology breaks in the chromosome, thereby reducing the chance of interlineage recombination. Conclusions: The allele types of the newly identified marker genes can be used to predict major lineages of M. avium. The single nucleotide polymorphism typing approach targeting multiallelic loci in recombination-cold regions will facilitate the epidemiological study of MAC, and may also be useful for equivalent studies of other nontuberculous mycobacteria potentially carrying mosaic genomes.

Original languageEnglish
Article number752
JournalBMC Genomics
Volume20
Issue number1
DOIs
Publication statusPublished - 2019 Oct 17

Fingerprint

Mycobacterium avium
Genetic Recombination
Alleles
Mycobacterium avium Complex
Genes
Genome
Chromosome Breakage
Nontuberculous Mycobacteria
Data Mining
Genetic Structures
Operon
Lung Diseases
Single Nucleotide Polymorphism
Epidemiologic Studies
Chromosomes
Proteins

Keywords

  • BAPS
  • Genetic population structure
  • Genotyping
  • MAC
  • Marker gene
  • MLVA
  • Mycobacterium
  • NTM
  • SNP
  • VNTR

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Cite this

The recombination-cold region as an epidemiological marker of recombinogenic opportunistic pathogen Mycobacterium avium. / Yano, Hirokazu; Suzuki, Haruo; Maruyama, Fumito; Iwamoto, Tomotada.

In: BMC Genomics, Vol. 20, No. 1, 752, 17.10.2019.

Research output: Contribution to journalArticle

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abstract = "Background: The rapid identification of lineage remains a challenge in the genotyping of clinical isolates of recombinogenic pathogens. The chromosome of Mycobacterium avium subsp. hominissuis (MAH), an agent of Mycobacterium avium complex (MAC) lung disease, is often mosaic and is composed of chromosomal segments originating from different lineages. This makes it difficult to infer the MAH lineage in a simple experimental set-up. To overcome this difficulty, we sought to identify chromosomal marker genes containing lineage-specific alleles by genome data mining. Results: We conducted genetic population structure analysis, phylogenetic analysis, and a survey of historical recombination using data from 125 global MAH isolates. Six MAH lineages (EA1, EA2, SC1, SC2, SC3, and SC4) were identified in the current dataset. One P-450 gene (locus-tag MAH-0788/MAV-0940) in the recombination-cold region was found to have multiple alleles that could discriminate five lineages. By combining the information about allele type from one additional gene, the six MAH lineages as well as other M. avium subspecies were distinguishable. A recombination-cold region of 116 kb contains an insertion hotspot and is flanked by a mammalian cell-entry protein operon where allelic variants have previously been reported to occur. Hence, we speculate that the acquisition of lineage-or strain-specific insertions has introduced homology breaks in the chromosome, thereby reducing the chance of interlineage recombination. Conclusions: The allele types of the newly identified marker genes can be used to predict major lineages of M. avium. The single nucleotide polymorphism typing approach targeting multiallelic loci in recombination-cold regions will facilitate the epidemiological study of MAC, and may also be useful for equivalent studies of other nontuberculous mycobacteria potentially carrying mosaic genomes.",
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AB - Background: The rapid identification of lineage remains a challenge in the genotyping of clinical isolates of recombinogenic pathogens. The chromosome of Mycobacterium avium subsp. hominissuis (MAH), an agent of Mycobacterium avium complex (MAC) lung disease, is often mosaic and is composed of chromosomal segments originating from different lineages. This makes it difficult to infer the MAH lineage in a simple experimental set-up. To overcome this difficulty, we sought to identify chromosomal marker genes containing lineage-specific alleles by genome data mining. Results: We conducted genetic population structure analysis, phylogenetic analysis, and a survey of historical recombination using data from 125 global MAH isolates. Six MAH lineages (EA1, EA2, SC1, SC2, SC3, and SC4) were identified in the current dataset. One P-450 gene (locus-tag MAH-0788/MAV-0940) in the recombination-cold region was found to have multiple alleles that could discriminate five lineages. By combining the information about allele type from one additional gene, the six MAH lineages as well as other M. avium subspecies were distinguishable. A recombination-cold region of 116 kb contains an insertion hotspot and is flanked by a mammalian cell-entry protein operon where allelic variants have previously been reported to occur. Hence, we speculate that the acquisition of lineage-or strain-specific insertions has introduced homology breaks in the chromosome, thereby reducing the chance of interlineage recombination. Conclusions: The allele types of the newly identified marker genes can be used to predict major lineages of M. avium. The single nucleotide polymorphism typing approach targeting multiallelic loci in recombination-cold regions will facilitate the epidemiological study of MAC, and may also be useful for equivalent studies of other nontuberculous mycobacteria potentially carrying mosaic genomes.

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