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Punctuated evolution and transitional hybrid network in an ancestral cell cycle of fungi.

Medina EM, Turner JJ, Gordân R, Skotheim JM, Buchler NE - Elife (2016)

Bottom Line: Cell cycle evolution in the fungal ancestor then proceeded through a hybrid network containing both SBF and its ancestral animal counterpart E2F, which is still maintained in many basal fungi.We hypothesize that a virally-derived SBF may have initially hijacked cell cycle control by activating transcription via the cis-regulatory elements targeted by the ancestral cell cycle regulator E2F, much like extant viral oncogenes.Consistent with this hypothesis, we show that SBF can regulate promoters with E2F binding sites in budding yeast.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Duke University, Durham, United States.

ABSTRACT
Although cell cycle control is an ancient, conserved, and essential process, some core animal and fungal cell cycle regulators share no more sequence identity than non-homologous proteins. Here, we show that evolution along the fungal lineage was punctuated by the early acquisition and entrainment of the SBF transcription factor through horizontal gene transfer. Cell cycle evolution in the fungal ancestor then proceeded through a hybrid network containing both SBF and its ancestral animal counterpart E2F, which is still maintained in many basal fungi. We hypothesize that a virally-derived SBF may have initially hijacked cell cycle control by activating transcription via the cis-regulatory elements targeted by the ancestral cell cycle regulator E2F, much like extant viral oncogenes. Consistent with this hypothesis, we show that SBF can regulate promoters with E2F binding sites in budding yeast.

No MeSH data available.


Reduced phylogeny of eukaryotic Cdc20-family APC regulators.We combined CDC20 and CDH1/FZR1 sequences from H. sapiens (3 members), A. thaliana (9 members), and S. cerevisiae (3 members) to create a eukaryotic CDC20-family APC regulator profile-HMM (pCDC20.hmm) following the procedure outlined in the Methods. A domain threshold of E-50 was used to identify CDC20 homologs. Our pCDC20 dataset has 350 sequences. This dataset was manually pruned to remove long-branches and problematic lineages. Our reduced CDC20 dataset (Figure 2—source data 4) has a total of 289 sequences. Columns with the top 20% Zorro score (608 positions) were used in our alignment. Confidence at nodes was assessed with multiple support metrics using different phylogenetic programs under LG model of evolution (aBayes and SH-aLRT metrics with PhyML, RBS with RAxML, Bayesian Posterior Probability with Phylobayes (13,638 sampled trees, meandiff=0.015, maxdiff=0.37)). Colored dots in branches indicate corresponding branch supports. Thick branches indicate significant support by at least two metrics, one parametric and one non-parametric; branch support thresholds are shown in the center of the figure; see Materials and methods.DOI:http://dx.doi.org/10.7554/eLife.09492.014
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fig2s5: Reduced phylogeny of eukaryotic Cdc20-family APC regulators.We combined CDC20 and CDH1/FZR1 sequences from H. sapiens (3 members), A. thaliana (9 members), and S. cerevisiae (3 members) to create a eukaryotic CDC20-family APC regulator profile-HMM (pCDC20.hmm) following the procedure outlined in the Methods. A domain threshold of E-50 was used to identify CDC20 homologs. Our pCDC20 dataset has 350 sequences. This dataset was manually pruned to remove long-branches and problematic lineages. Our reduced CDC20 dataset (Figure 2—source data 4) has a total of 289 sequences. Columns with the top 20% Zorro score (608 positions) were used in our alignment. Confidence at nodes was assessed with multiple support metrics using different phylogenetic programs under LG model of evolution (aBayes and SH-aLRT metrics with PhyML, RBS with RAxML, Bayesian Posterior Probability with Phylobayes (13,638 sampled trees, meandiff=0.015, maxdiff=0.37)). Colored dots in branches indicate corresponding branch supports. Thick branches indicate significant support by at least two metrics, one parametric and one non-parametric; branch support thresholds are shown in the center of the figure; see Materials and methods.DOI:http://dx.doi.org/10.7554/eLife.09492.014

Mentions: While we did not find either of the fungal regulators (SBF and Whi5) outside of Fungi, we did find animal-like cell cycle regulators in Archaeplastida, Amoebozoa, SAR, Haptophyta, Cryptophyta, Excavata and Metazoa (Figure 2). For example, the cyclin sub-families (A, B, D, and E) known to regulate the cell cycle in metazoans (for cyclin phylogeny see Figure 2—figure supplement 2) are found across the major branches of eukaryotes. We also found examples of all three sub-families of E2F transcription factors (E2F1-6, DP, E2F7/8) and the pRb family of pocket proteins (for E2F/DP and pRb phylogeny see Figure 2—figure supplement 3 and Figure 2—figure supplement 4). Nearly all species contain the APC specificity subunits Cdc20 and Cdh1/Fzr1, which regulate exit from mitosis and maintain low Cdk activity in G1 (for Cdc20-family APC phylogeny see Figure 2—figure supplement 5). Taken together, these data indicate that LECA cell cycle regulation was based on multiple cyclin families, as well as regulation by the APC complex and members of the pRb and E2F families. More broadly, our phylogenetic analyses tend to place the fungal regulators as sister groups to the metazoan regulators, as would be expected from the known eukaryotic species tree. These phylogenies are in agreement with the hypothesis that many fungal and metazoan regulators were vertically inherited from an opisthokont ancestor rather than loss of these regulators in fungi followed by secondary acquisition through horizontal gene transfer.10.7554/eLife.09492.004Figure 2.Animal and plant G1/S regulatory network components were present in the last eukaryotic common ancestor.


Punctuated evolution and transitional hybrid network in an ancestral cell cycle of fungi.

Medina EM, Turner JJ, Gordân R, Skotheim JM, Buchler NE - Elife (2016)

Reduced phylogeny of eukaryotic Cdc20-family APC regulators.We combined CDC20 and CDH1/FZR1 sequences from H. sapiens (3 members), A. thaliana (9 members), and S. cerevisiae (3 members) to create a eukaryotic CDC20-family APC regulator profile-HMM (pCDC20.hmm) following the procedure outlined in the Methods. A domain threshold of E-50 was used to identify CDC20 homologs. Our pCDC20 dataset has 350 sequences. This dataset was manually pruned to remove long-branches and problematic lineages. Our reduced CDC20 dataset (Figure 2—source data 4) has a total of 289 sequences. Columns with the top 20% Zorro score (608 positions) were used in our alignment. Confidence at nodes was assessed with multiple support metrics using different phylogenetic programs under LG model of evolution (aBayes and SH-aLRT metrics with PhyML, RBS with RAxML, Bayesian Posterior Probability with Phylobayes (13,638 sampled trees, meandiff=0.015, maxdiff=0.37)). Colored dots in branches indicate corresponding branch supports. Thick branches indicate significant support by at least two metrics, one parametric and one non-parametric; branch support thresholds are shown in the center of the figure; see Materials and methods.DOI:http://dx.doi.org/10.7554/eLife.09492.014
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4862756&req=5

fig2s5: Reduced phylogeny of eukaryotic Cdc20-family APC regulators.We combined CDC20 and CDH1/FZR1 sequences from H. sapiens (3 members), A. thaliana (9 members), and S. cerevisiae (3 members) to create a eukaryotic CDC20-family APC regulator profile-HMM (pCDC20.hmm) following the procedure outlined in the Methods. A domain threshold of E-50 was used to identify CDC20 homologs. Our pCDC20 dataset has 350 sequences. This dataset was manually pruned to remove long-branches and problematic lineages. Our reduced CDC20 dataset (Figure 2—source data 4) has a total of 289 sequences. Columns with the top 20% Zorro score (608 positions) were used in our alignment. Confidence at nodes was assessed with multiple support metrics using different phylogenetic programs under LG model of evolution (aBayes and SH-aLRT metrics with PhyML, RBS with RAxML, Bayesian Posterior Probability with Phylobayes (13,638 sampled trees, meandiff=0.015, maxdiff=0.37)). Colored dots in branches indicate corresponding branch supports. Thick branches indicate significant support by at least two metrics, one parametric and one non-parametric; branch support thresholds are shown in the center of the figure; see Materials and methods.DOI:http://dx.doi.org/10.7554/eLife.09492.014
Mentions: While we did not find either of the fungal regulators (SBF and Whi5) outside of Fungi, we did find animal-like cell cycle regulators in Archaeplastida, Amoebozoa, SAR, Haptophyta, Cryptophyta, Excavata and Metazoa (Figure 2). For example, the cyclin sub-families (A, B, D, and E) known to regulate the cell cycle in metazoans (for cyclin phylogeny see Figure 2—figure supplement 2) are found across the major branches of eukaryotes. We also found examples of all three sub-families of E2F transcription factors (E2F1-6, DP, E2F7/8) and the pRb family of pocket proteins (for E2F/DP and pRb phylogeny see Figure 2—figure supplement 3 and Figure 2—figure supplement 4). Nearly all species contain the APC specificity subunits Cdc20 and Cdh1/Fzr1, which regulate exit from mitosis and maintain low Cdk activity in G1 (for Cdc20-family APC phylogeny see Figure 2—figure supplement 5). Taken together, these data indicate that LECA cell cycle regulation was based on multiple cyclin families, as well as regulation by the APC complex and members of the pRb and E2F families. More broadly, our phylogenetic analyses tend to place the fungal regulators as sister groups to the metazoan regulators, as would be expected from the known eukaryotic species tree. These phylogenies are in agreement with the hypothesis that many fungal and metazoan regulators were vertically inherited from an opisthokont ancestor rather than loss of these regulators in fungi followed by secondary acquisition through horizontal gene transfer.10.7554/eLife.09492.004Figure 2.Animal and plant G1/S regulatory network components were present in the last eukaryotic common ancestor.

Bottom Line: Cell cycle evolution in the fungal ancestor then proceeded through a hybrid network containing both SBF and its ancestral animal counterpart E2F, which is still maintained in many basal fungi.We hypothesize that a virally-derived SBF may have initially hijacked cell cycle control by activating transcription via the cis-regulatory elements targeted by the ancestral cell cycle regulator E2F, much like extant viral oncogenes.Consistent with this hypothesis, we show that SBF can regulate promoters with E2F binding sites in budding yeast.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Duke University, Durham, United States.

ABSTRACT
Although cell cycle control is an ancient, conserved, and essential process, some core animal and fungal cell cycle regulators share no more sequence identity than non-homologous proteins. Here, we show that evolution along the fungal lineage was punctuated by the early acquisition and entrainment of the SBF transcription factor through horizontal gene transfer. Cell cycle evolution in the fungal ancestor then proceeded through a hybrid network containing both SBF and its ancestral animal counterpart E2F, which is still maintained in many basal fungi. We hypothesize that a virally-derived SBF may have initially hijacked cell cycle control by activating transcription via the cis-regulatory elements targeted by the ancestral cell cycle regulator E2F, much like extant viral oncogenes. Consistent with this hypothesis, we show that SBF can regulate promoters with E2F binding sites in budding yeast.

No MeSH data available.