Research ArticleHEALTH AND MEDICINE

Global expansion of Mycobacterium tuberculosis lineage 4 shaped by colonial migration and local adaptation

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Science Advances  17 Oct 2018:
Vol. 4, no. 10, eaat5869
DOI: 10.1126/sciadv.aat5869
  • Fig. 1 Sampling overview and phylogeography of the global L4 dataset.

    In the map, sampled countries are colored by continent, and sample sizes are indicated. In the temporal phylogeny, branches are colored to match the most likely geographic location inferred using BASTA. MDR clusters identified in the dataset are highlighted with black background shading. A large black asterisk highlights the branch leading to the DS6Quebec clade that was used to assess robustness of dating analyses, whereas yellow dots indicate independent introductions of the KZN ancestor to South Africa and South America (see main text for details).

  • Fig. 2 Within-country diversity as assessed by mean pairwise SNP distances (only including well-sampled countries).

    Vertical dashed lines indicate median values. Embedded pie charts summarize sublineage distribution within each country. The Simpsons diversity index (1-D) was calculated at the level of subspecies and the estimate indicated in the top of each county panel (where higher values correspond to increased diversity).

  • Fig. 3 L4 migration.

    (A) Heatmap summarizing the overall migration load between continents as inferred in BASTA. (B) Temporal overview of L4 migration out of Europe. The establishment of strains of interest discussed in the text is highlighted. As the exact timing of the first American migrations was uncertain, the mean of the first three inferred migration events to each of the two subcontinents is reported as an approximation of the earliest migration events to the Americas. (C) Out-of-Europe migration to Southeast Asia, Africa, and South America over time. The plots also show within-continent migration/transmission in the receiving continents to illustrate the relative importance of repeated L4 import on continental L4 load over time. SE, southeast.

  • Fig. 4 Transmission of resistance.

    (Top) Independent emergence of AMR over time based on the age of nodes where resistance mutations were inferred to have emerged. (Middle) Inferred cross-border transmission of the descendants of susceptible and resistant ancestors as a function of node age. The size of the dots indicates the number of inferred cross-continental migration events occurring among ancestors of each node. Individual dots are colored by the drug to which they cause resistance. (Bottom) The number of descendants divided by node age for inferred nodes with or without resistance mutations as a proxy for transmissibility.

Supplementary Materials

  • Supplementary material for this article is available at http://advances.sciencemag.org/cgi/content/full/4/10/eaat5869/DC1

    Supplementary Text

    Fig. S1. Genome-wide assessment of homoplasic mutations presented as gene-wise parsimony scores as a function of θ and nucleotide diversity (π).

    Fig. S2. Node descendants as a function of node age for clones harboring different groups of lldD2 mutations.

    Fig. S3. Tip-randomization results.

    Fig. S4. Root-to-tip analysis performed on a global down-sampled collection containing 269 genomes.

    Fig. S5. Migration matrices inferred with DTA and BASTA visualized as heatmaps.

    Fig. S6. Inferred migration of L4 over time from Europe to North and South America, as well as within the continents, using BASTA.

    Fig. S7. Phylogeographic reconstruction of the RdRio family.

    Fig. S8. Full temporal phylogeny of L4 including node age 95% HPD intervals.

    Fig. S9. Histogram summarizing the emergence of lldD2 mutations over time.

    Dataset S1. List of strains.

    Dataset S2. Results from population genomic inferences.

    Dataset S3. Location of lldD2 mutation emergence.

    References (6566)

  • Supplementary Materials

    The PDF file includes:

    • Supplementary Text
    • Fig. S1. Genome-wide assessment of homoplasic mutations presented as gene-wise parsimony scores as a function of θ and nucleotide diversity (π).
    • Fig. S2. Node descendants as a function of node age for clones harboring different groups of lldD2 mutations.
    • Fig. S3. Tip-randomization results.
    • Fig. S4. Root-to-tip analysis performed on a global down-sampled collection containing 269 genomes.
    • Fig. S5. Migration matrices inferred with DTA and BASTA visualized as heatmaps.
    • Fig. S6. Inferred migration of L4 over time from Europe to North and South America, as well as within the continents, using BASTA.
    • Fig. S7. Phylogeographic reconstruction of the RdRio family.
    • Fig. S8. Full temporal phylogeny of L4 including node age 95% HPD intervals.
    • Fig. S9. Histogram summarizing the emergence of lldD2 mutations over time.
    • References (6566)

    Download PDF

    Other Supplementary Material for this manuscript includes the following:

    • Dataset S1 (Microsoft Excel format). List of strains.
    • Dataset S2 (.csv format). Results from population genomic inferences.
    • Dataset S3 (Microsoft Excel format). Location of lldD2 mutation emergence.

    Files in this Data Supplement:

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