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Genome Evolution and Innovation across the Four Major Lineages of Cryptococcus gattii.

Farrer RA, Desjardins CA, Sakthikumar S, Gujja S, Saif S, Zeng Q, Chen Y, Voelz K, Heitman J, May RC, Fisher MC, Cuomo CA - MBio (2015)

Bottom Line: By identifying syntenic regions across assemblies, we found 15 structural rearrangements, which were almost exclusive to the VGI-III-IV lineages.In addition, we found evidence for recent transcontinental spread, mitochondrial genetic exchange, and positive selection in multidrug transporters.Our results suggest that gene expansion/contraction and positive selection are diversifying the mechanisms of pathogenicity across this species complex.

View Article: PubMed Central - PubMed

Affiliation: Genome Sequencing and Analysis Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

No MeSH data available.


Related in: MedlinePlus

Topological discordance between the nuclear (left) and mitochondrial (right) genomes of C. gattii. Orange, VGI; red, VGII; green, VGIII; yellow, VGIV. (A) RAxML trees for the nuclear and mitochondrial genomes (boldface branches, 100% bootstrap support using 1,000 replicates). (B) Principal component analysis for the nuclear and mitochondrial genomes. (C) SNPs across the mitochondrial genomes of 7 isolates, including representatives from each lineage. Differences from the nuclear tree were most visible in four isolates: progeny 5, E566, Ru294, and EJB2. SNPs are colored according to the lineage to which they are unique. VGII-auxiliary (VGI-VGII, VGII-VGIII, VGII-VGIV, VGI-VGII-VGIII, VGI-VGII-VGIV, VGII-VGIII-VGIV, and VGI-VGII-VGIII-VGIV) is also colored red, while VGIV-auxiliary (VGI-VGIV, VGIII-VGIV, and VGI-VGIII-VGIV) is colored yellow. N, NADH ubiquinone oxidoreductase; ND, NADH dehydrogenase; A, ATP synthase; CCO, cytochrome c oxidase; Cb, cytochrome b; SRP, small ribosomal protein; c, chain; s, subunit.
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fig3: Topological discordance between the nuclear (left) and mitochondrial (right) genomes of C. gattii. Orange, VGI; red, VGII; green, VGIII; yellow, VGIV. (A) RAxML trees for the nuclear and mitochondrial genomes (boldface branches, 100% bootstrap support using 1,000 replicates). (B) Principal component analysis for the nuclear and mitochondrial genomes. (C) SNPs across the mitochondrial genomes of 7 isolates, including representatives from each lineage. Differences from the nuclear tree were most visible in four isolates: progeny 5, E566, Ru294, and EJB2. SNPs are colored according to the lineage to which they are unique. VGII-auxiliary (VGI-VGII, VGII-VGIII, VGII-VGIV, VGI-VGII-VGIII, VGI-VGII-VGIV, VGII-VGIII-VGIV, and VGI-VGII-VGIII-VGIV) is also colored red, while VGIV-auxiliary (VGI-VGIV, VGIII-VGIV, and VGI-VGIII-VGIV) is colored yellow. N, NADH ubiquinone oxidoreductase; ND, NADH dehydrogenase; A, ATP synthase; CCO, cytochrome c oxidase; Cb, cytochrome b; SRP, small ribosomal protein; c, chain; s, subunit.

Mentions: The phylogeny estimated from nuclear site variation was next compared to that of mitochondrial genome variation. While the topologies of the mitochondrial and nuclear trees were similar, there was substantial variation in branch lengths between the two (Fig. 3A), most notably a large amount of mitochondrial diversity in VGI relative to nuclear diversity. Evaluation with principal component analysis (PCA) revealed that lineages were less discernible based on mitochondrial than on nuclear sequence (Fig. 3B), possibly in part due to recombination between these groups. Three of the six VGI isolates (E566, Ru294, and EJB2) showed greater mitochondrial sequence similarity to VGII than did their nuclear genomes. Ru294 also had a high number of shared SNPs with VGIV, including a stretch across ATP synthase subunit 6 (Fig. 3C). EJB2 and E566 also had fewer SNPs relative to VGII than did other VGI isolates (Fig. 3C). Each of these isolates has more than 100-fold depth of coverage, suggesting that this is not an artifact of lower sequencing or alignment depth. Pairwise FST values from VGI-VGIII (0.642), VGI-VGIV (0.672), and VGIII-VGIV (0.658) suggest that the mitochondria appear to be more recombinogenic than their nuclear counterparts (FST = 0.885, 0.894, and 0.885, respectively).


Genome Evolution and Innovation across the Four Major Lineages of Cryptococcus gattii.

Farrer RA, Desjardins CA, Sakthikumar S, Gujja S, Saif S, Zeng Q, Chen Y, Voelz K, Heitman J, May RC, Fisher MC, Cuomo CA - MBio (2015)

Topological discordance between the nuclear (left) and mitochondrial (right) genomes of C. gattii. Orange, VGI; red, VGII; green, VGIII; yellow, VGIV. (A) RAxML trees for the nuclear and mitochondrial genomes (boldface branches, 100% bootstrap support using 1,000 replicates). (B) Principal component analysis for the nuclear and mitochondrial genomes. (C) SNPs across the mitochondrial genomes of 7 isolates, including representatives from each lineage. Differences from the nuclear tree were most visible in four isolates: progeny 5, E566, Ru294, and EJB2. SNPs are colored according to the lineage to which they are unique. VGII-auxiliary (VGI-VGII, VGII-VGIII, VGII-VGIV, VGI-VGII-VGIII, VGI-VGII-VGIV, VGII-VGIII-VGIV, and VGI-VGII-VGIII-VGIV) is also colored red, while VGIV-auxiliary (VGI-VGIV, VGIII-VGIV, and VGI-VGIII-VGIV) is colored yellow. N, NADH ubiquinone oxidoreductase; ND, NADH dehydrogenase; A, ATP synthase; CCO, cytochrome c oxidase; Cb, cytochrome b; SRP, small ribosomal protein; c, chain; s, subunit.
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Related In: Results  -  Collection

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fig3: Topological discordance between the nuclear (left) and mitochondrial (right) genomes of C. gattii. Orange, VGI; red, VGII; green, VGIII; yellow, VGIV. (A) RAxML trees for the nuclear and mitochondrial genomes (boldface branches, 100% bootstrap support using 1,000 replicates). (B) Principal component analysis for the nuclear and mitochondrial genomes. (C) SNPs across the mitochondrial genomes of 7 isolates, including representatives from each lineage. Differences from the nuclear tree were most visible in four isolates: progeny 5, E566, Ru294, and EJB2. SNPs are colored according to the lineage to which they are unique. VGII-auxiliary (VGI-VGII, VGII-VGIII, VGII-VGIV, VGI-VGII-VGIII, VGI-VGII-VGIV, VGII-VGIII-VGIV, and VGI-VGII-VGIII-VGIV) is also colored red, while VGIV-auxiliary (VGI-VGIV, VGIII-VGIV, and VGI-VGIII-VGIV) is colored yellow. N, NADH ubiquinone oxidoreductase; ND, NADH dehydrogenase; A, ATP synthase; CCO, cytochrome c oxidase; Cb, cytochrome b; SRP, small ribosomal protein; c, chain; s, subunit.
Mentions: The phylogeny estimated from nuclear site variation was next compared to that of mitochondrial genome variation. While the topologies of the mitochondrial and nuclear trees were similar, there was substantial variation in branch lengths between the two (Fig. 3A), most notably a large amount of mitochondrial diversity in VGI relative to nuclear diversity. Evaluation with principal component analysis (PCA) revealed that lineages were less discernible based on mitochondrial than on nuclear sequence (Fig. 3B), possibly in part due to recombination between these groups. Three of the six VGI isolates (E566, Ru294, and EJB2) showed greater mitochondrial sequence similarity to VGII than did their nuclear genomes. Ru294 also had a high number of shared SNPs with VGIV, including a stretch across ATP synthase subunit 6 (Fig. 3C). EJB2 and E566 also had fewer SNPs relative to VGII than did other VGI isolates (Fig. 3C). Each of these isolates has more than 100-fold depth of coverage, suggesting that this is not an artifact of lower sequencing or alignment depth. Pairwise FST values from VGI-VGIII (0.642), VGI-VGIV (0.672), and VGIII-VGIV (0.658) suggest that the mitochondria appear to be more recombinogenic than their nuclear counterparts (FST = 0.885, 0.894, and 0.885, respectively).

Bottom Line: By identifying syntenic regions across assemblies, we found 15 structural rearrangements, which were almost exclusive to the VGI-III-IV lineages.In addition, we found evidence for recent transcontinental spread, mitochondrial genetic exchange, and positive selection in multidrug transporters.Our results suggest that gene expansion/contraction and positive selection are diversifying the mechanisms of pathogenicity across this species complex.

View Article: PubMed Central - PubMed

Affiliation: Genome Sequencing and Analysis Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

No MeSH data available.


Related in: MedlinePlus