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Highly recombinant VGII Cryptococcus gattii population develops clonal outbreak clusters through both sexual macroevolution and asexual microevolution.

Billmyre RB, Croll D, Li W, Mieczkowski P, Carter DA, Cuomo CA, Kronstad JW, Heitman J - MBio (2014)

Bottom Line: We found that VGIIa/b/c populations show evidence of clonal expansion in the PNW.We also found that the genomes of two basal VGII isolates from HIV(+) patients contain an introgression tract spanning three genes.This work shows that multiple processes can contribute to the emergence of an outbreak.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA heitm001@duke.edu.

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Regions of reduced SNP density provide evidence for ancestral sexual reproduction. (A) SNP density is plotted relative to the R265 reference genome. Clonal groups are collapsed to the SNPs shared by all members of the group. Regions of unexpectedly low levels of polymorphism are boxed for emphasis. (B) Maximum likelihood phylogenies generated from regions of depressed SNP density demarcated in panel A. Bootstrap values are based on 500 bootstraps. The scale bar indicates the number of substitutions per nucleotide position. Outbreak groups are highlighted in larger font, as well as individual global isolates that contribute to the identity island.
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fig6: Regions of reduced SNP density provide evidence for ancestral sexual reproduction. (A) SNP density is plotted relative to the R265 reference genome. Clonal groups are collapsed to the SNPs shared by all members of the group. Regions of unexpectedly low levels of polymorphism are boxed for emphasis. (B) Maximum likelihood phylogenies generated from regions of depressed SNP density demarcated in panel A. Bootstrap values are based on 500 bootstraps. The scale bar indicates the number of substitutions per nucleotide position. Outbreak groups are highlighted in larger font, as well as individual global isolates that contribute to the identity island.

Mentions: While strains within each of the five clonal clusters of C. gattii are highly related to each other, comparisons among clusters revealed substantial differences. However, the sites differentiating these clusters were not uniformly dense across the genome. This is demonstrated by incongruity between phylogenies inferred from different portions of the genome (Fig. 5), suggesting that ancestral recombination among the clonal lineages has resulted in some portions of the genome being more similar between two clonal groups than the others. Further evidence is provided by examining SNP density between isolates. This analysis demonstrates the presence of islands of identity between any two individual isolates where diversity is considerably lower than the genome-wide average (Fig. 6A). Inferring phylogenies from these regions of depressed polymorphism reveals uniquely close relationships among strains (Fig. 6B). This suggests that sexual reproduction likely contributed to the production of the ancestor of each clonal cluster, with subsequent mitotic clonal expansion of these isolates to spread throughout the environment. Notably, none of the outbreak clusters has an individual partner strain or cluster that contributes a large portion of the genome (i.e., 50% for one cross, 25% for two crosses, etc.). This suggests that either sampling has captured only a small portion of the VGII population or some of these intermediate strains may no longer exist.


Highly recombinant VGII Cryptococcus gattii population develops clonal outbreak clusters through both sexual macroevolution and asexual microevolution.

Billmyre RB, Croll D, Li W, Mieczkowski P, Carter DA, Cuomo CA, Kronstad JW, Heitman J - MBio (2014)

Regions of reduced SNP density provide evidence for ancestral sexual reproduction. (A) SNP density is plotted relative to the R265 reference genome. Clonal groups are collapsed to the SNPs shared by all members of the group. Regions of unexpectedly low levels of polymorphism are boxed for emphasis. (B) Maximum likelihood phylogenies generated from regions of depressed SNP density demarcated in panel A. Bootstrap values are based on 500 bootstraps. The scale bar indicates the number of substitutions per nucleotide position. Outbreak groups are highlighted in larger font, as well as individual global isolates that contribute to the identity island.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4128362&req=5

fig6: Regions of reduced SNP density provide evidence for ancestral sexual reproduction. (A) SNP density is plotted relative to the R265 reference genome. Clonal groups are collapsed to the SNPs shared by all members of the group. Regions of unexpectedly low levels of polymorphism are boxed for emphasis. (B) Maximum likelihood phylogenies generated from regions of depressed SNP density demarcated in panel A. Bootstrap values are based on 500 bootstraps. The scale bar indicates the number of substitutions per nucleotide position. Outbreak groups are highlighted in larger font, as well as individual global isolates that contribute to the identity island.
Mentions: While strains within each of the five clonal clusters of C. gattii are highly related to each other, comparisons among clusters revealed substantial differences. However, the sites differentiating these clusters were not uniformly dense across the genome. This is demonstrated by incongruity between phylogenies inferred from different portions of the genome (Fig. 5), suggesting that ancestral recombination among the clonal lineages has resulted in some portions of the genome being more similar between two clonal groups than the others. Further evidence is provided by examining SNP density between isolates. This analysis demonstrates the presence of islands of identity between any two individual isolates where diversity is considerably lower than the genome-wide average (Fig. 6A). Inferring phylogenies from these regions of depressed polymorphism reveals uniquely close relationships among strains (Fig. 6B). This suggests that sexual reproduction likely contributed to the production of the ancestor of each clonal cluster, with subsequent mitotic clonal expansion of these isolates to spread throughout the environment. Notably, none of the outbreak clusters has an individual partner strain or cluster that contributes a large portion of the genome (i.e., 50% for one cross, 25% for two crosses, etc.). This suggests that either sampling has captured only a small portion of the VGII population or some of these intermediate strains may no longer exist.

Bottom Line: We found that VGIIa/b/c populations show evidence of clonal expansion in the PNW.We also found that the genomes of two basal VGII isolates from HIV(+) patients contain an introgression tract spanning three genes.This work shows that multiple processes can contribute to the emergence of an outbreak.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA heitm001@duke.edu.

Show MeSH
Related in: MedlinePlus