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High functional diversity in Mycobacterium tuberculosis driven by genetic drift and human demography.

Hershberg R, Lipatov M, Small PM, Sheffer H, Niemann S, Homolka S, Roach JC, Kremer K, Petrov DA, Feldman MW, Gagneux S - PLoS Biol. (2008)

Bottom Line: We surveyed sequence diversity within a global collection of strains belonging to MTBC using seven megabase pairs of DNA sequence data.We show that the members of MTBC affecting humans are more genetically diverse than generally assumed, and that this diversity can be linked to human demographic and migratory events.We further demonstrate that these organisms are under extremely reduced purifying selection and that, as a result of increased genetic drift, much of this genetic diversity is likely to have functional consequences.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Stanford University, Stanford, California, USA.

ABSTRACT
Mycobacterium tuberculosis infects one third of the human world population and kills someone every 15 seconds. For more than a century, scientists and clinicians have been distinguishing between the human- and animal-adapted members of the M. tuberculosis complex (MTBC). However, all human-adapted strains of MTBC have traditionally been considered to be essentially identical. We surveyed sequence diversity within a global collection of strains belonging to MTBC using seven megabase pairs of DNA sequence data. We show that the members of MTBC affecting humans are more genetically diverse than generally assumed, and that this diversity can be linked to human demographic and migratory events. We further demonstrate that these organisms are under extremely reduced purifying selection and that, as a result of increased genetic drift, much of this genetic diversity is likely to have functional consequences. Our findings suggest that the current increases in human population, urbanization, and global travel, combined with the population genetic characteristics of M. tuberculosis described here, could contribute to the emergence and spread of drug-resistant tuberculosis.

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Related in: MedlinePlus

Maximum Parsimony Phylogeny of M. tuberculosis Complex Using 89 Concatenated Gene Sequences in 108 StrainsThe branches are colored according to the main lineages defined previously based on our genomic deletion analysis, except for the animal-adapted strains, which are indicated in orange. The main clades are labeled according to their dominance in particular geographic areas. The branch leading to M. canettii has been truncated in the figure because of the large numbers of changes that separate this hypothesized outgroup from the rest of the phylogeny (Table S4). Ancient and modern strain lineages are indicated. The green and brown lineages correspond to strains traditionally known as M. africanum [21].
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pbio-0060311-g001: Maximum Parsimony Phylogeny of M. tuberculosis Complex Using 89 Concatenated Gene Sequences in 108 StrainsThe branches are colored according to the main lineages defined previously based on our genomic deletion analysis, except for the animal-adapted strains, which are indicated in orange. The main clades are labeled according to their dominance in particular geographic areas. The branch leading to M. canettii has been truncated in the figure because of the large numbers of changes that separate this hypothesized outgroup from the rest of the phylogeny (Table S4). Ancient and modern strain lineages are indicated. The green and brown lineages correspond to strains traditionally known as M. africanum [21].

Mentions: We first used the concatenated DNA sequences of the 89 genes for each of the 108 strains and conducted a maximum parsimony analysis. Our analysis produced a single phylogenetic tree with a homoplasy index of 0.0043 (Figure 1). This phylogenetic tree is completely congruent with the one we constructed using the neighbor-joining method (Figure S2) as well as with the deletion-based analysis we reported previously (Figure 1, Table S1) [19]. The negligible degree of homoplasy observed in our sequence-based tree, and the fact that our sequence-based and deletion-based trees are congruent further supports the highly clonal population structure of MTBC [39,40]. The primary branches of our sequence-based tree are also consistent with earlier studies that classified M. tuberculosis into “ancient” and “modern” forms based on the presence or absence of a genomic deletion known as TbD1 [8]. However, because our new sequence data allow us to better interpret genetic distances between lineages, we find that the difference between ancient and modern MTBC is more pronounced than one would assume on the basis of the presence of a single genomic deletion (Figure 1).


High functional diversity in Mycobacterium tuberculosis driven by genetic drift and human demography.

Hershberg R, Lipatov M, Small PM, Sheffer H, Niemann S, Homolka S, Roach JC, Kremer K, Petrov DA, Feldman MW, Gagneux S - PLoS Biol. (2008)

Maximum Parsimony Phylogeny of M. tuberculosis Complex Using 89 Concatenated Gene Sequences in 108 StrainsThe branches are colored according to the main lineages defined previously based on our genomic deletion analysis, except for the animal-adapted strains, which are indicated in orange. The main clades are labeled according to their dominance in particular geographic areas. The branch leading to M. canettii has been truncated in the figure because of the large numbers of changes that separate this hypothesized outgroup from the rest of the phylogeny (Table S4). Ancient and modern strain lineages are indicated. The green and brown lineages correspond to strains traditionally known as M. africanum [21].
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2602723&req=5

pbio-0060311-g001: Maximum Parsimony Phylogeny of M. tuberculosis Complex Using 89 Concatenated Gene Sequences in 108 StrainsThe branches are colored according to the main lineages defined previously based on our genomic deletion analysis, except for the animal-adapted strains, which are indicated in orange. The main clades are labeled according to their dominance in particular geographic areas. The branch leading to M. canettii has been truncated in the figure because of the large numbers of changes that separate this hypothesized outgroup from the rest of the phylogeny (Table S4). Ancient and modern strain lineages are indicated. The green and brown lineages correspond to strains traditionally known as M. africanum [21].
Mentions: We first used the concatenated DNA sequences of the 89 genes for each of the 108 strains and conducted a maximum parsimony analysis. Our analysis produced a single phylogenetic tree with a homoplasy index of 0.0043 (Figure 1). This phylogenetic tree is completely congruent with the one we constructed using the neighbor-joining method (Figure S2) as well as with the deletion-based analysis we reported previously (Figure 1, Table S1) [19]. The negligible degree of homoplasy observed in our sequence-based tree, and the fact that our sequence-based and deletion-based trees are congruent further supports the highly clonal population structure of MTBC [39,40]. The primary branches of our sequence-based tree are also consistent with earlier studies that classified M. tuberculosis into “ancient” and “modern” forms based on the presence or absence of a genomic deletion known as TbD1 [8]. However, because our new sequence data allow us to better interpret genetic distances between lineages, we find that the difference between ancient and modern MTBC is more pronounced than one would assume on the basis of the presence of a single genomic deletion (Figure 1).

Bottom Line: We surveyed sequence diversity within a global collection of strains belonging to MTBC using seven megabase pairs of DNA sequence data.We show that the members of MTBC affecting humans are more genetically diverse than generally assumed, and that this diversity can be linked to human demographic and migratory events.We further demonstrate that these organisms are under extremely reduced purifying selection and that, as a result of increased genetic drift, much of this genetic diversity is likely to have functional consequences.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Stanford University, Stanford, California, USA.

ABSTRACT
Mycobacterium tuberculosis infects one third of the human world population and kills someone every 15 seconds. For more than a century, scientists and clinicians have been distinguishing between the human- and animal-adapted members of the M. tuberculosis complex (MTBC). However, all human-adapted strains of MTBC have traditionally been considered to be essentially identical. We surveyed sequence diversity within a global collection of strains belonging to MTBC using seven megabase pairs of DNA sequence data. We show that the members of MTBC affecting humans are more genetically diverse than generally assumed, and that this diversity can be linked to human demographic and migratory events. We further demonstrate that these organisms are under extremely reduced purifying selection and that, as a result of increased genetic drift, much of this genetic diversity is likely to have functional consequences. Our findings suggest that the current increases in human population, urbanization, and global travel, combined with the population genetic characteristics of M. tuberculosis described here, could contribute to the emergence and spread of drug-resistant tuberculosis.

Show MeSH
Related in: MedlinePlus