Punctuated evolution and transitional hybrid network in an ancestral cell cycle of fungi
- Duke University, United States
- Stanford University, United States
Figures
Figure 1
Topology of G1/S regulatory network in mammals and budding yeast is conserved, yet many regulators exhibit no detectable sequence homology.
Schematic diagram illustrating the extensive similarities between (A) animal and (B) budding yeast G1/S cell cycle control networks. Similar coloring denotes members of a similar family or …
Figure 2 with 6 supplements
Animal and plant G1/S regulatory network components were present in the last eukaryotic common ancestor.
Distribution of cell cycle regulators across the eukaryotic species tree (Adl et al., 2012). Animals (Metazoa) and yeasts (Fungi) are sister groups (Opisthokonta), and are distantly related to …
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Figure 2—source data 1
Reduced set of eukaryotic cell cycle cyclins for phylogenetic analysis.
These files contain the protein sequences used to create molecular phylogeny in Figure 2—figure supplement 2.
- https://doi.org/10.7554/eLife.09492.005
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Figure 2—source data 2
Complete set of eukaryotic E2F/DP transcription factors for phylogenetic analysis.
These files contain the protein sequences used to create molecular phylogeny in Figure 2—figure supplement 3.
- https://doi.org/10.7554/eLife.09492.006
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Figure 2—source data 3
Complete set of eukaryotic Rb inhibitors for phylogenetic analysis.
These files contain the protein sequences used to create molecular phylogeny in Figure 2—figure supplement 4.
- https://doi.org/10.7554/eLife.09492.007
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Figure 2—source data 4
Reduced set of eukaryotic Cdc20-family APC regulators for phylogenetic analysis.
These files contain the protein sequences used to create molecular phylogeny in Figure 2—figure supplement 5.
- https://doi.org/10.7554/eLife.09492.008
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Figure 2—source data 5
Reduced set of eukaryotic cyclin-dependent kinases for phylogenetic analysis.
These files contain the protein sequences used to create molecular phylogeny in Figure 2—figure supplement 6.
- https://doi.org/10.7554/eLife.09492.009
Figure 2—figure supplement 1
Comparative genomic data of G1/S regulators across eukaryotes.
Each entry lists the number of sub-family members (column) for each eukaryotic genome (row). Grey rows list the sub-family gene names in H. sapiens and A. thaliana. Additional cyclin sub-family …
Figure 2—figure supplement 2
Reduced phylogeny of eukaryotic cell cycle cyclins.
The cell division cycle (CDC) cyclin family consists of several sub-families with a well-characterized cyclin box: (1) CycA (H. sapiens, A. thaliana), (2) CycB and CLB (H. sapiens, A. thaliana, S. …
Figure 2—figure supplement 3
Phylogeny of eukaryotic E2F/DP transcription factors.
E2F-DP is a winged helix-turn-helix DNA-binding domain that is conserved across eukaryotes (van den Heuvel and Dyson, 2008). There are three sub-families within the E2F-DP family: (1) the E2F …
Figure 2—figure supplement 4
Phylogeny of eukaryotic Rb inhibitors.
H. sapiens has Rb1, RBL1 (p107), and RBL2 (p130), and A. thaliana has RBR1. The model fungi S. cerevisiae and S. pombe do not have any obvious retinoblastoma pocket proteins. We needed more …
Figure 2—figure supplement 5
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 …
Figure 2—figure supplement 6
Reduced phylogeny of eukaryotic cyclin-dependent kinases.
To create a profile-HMM (pCDCCDK.hmm) for eukaryotic cell cycle CDK, we combined Cdk1-3, Cdk4, Cdk6 sequences from H. sapiens, CdkA and CdkB from A. thaliana, Cdc28 from S. cerevisiae, and Cdc2 from …
Figure 3 with 4 supplements
Fungal ancestor evolved novel G1/S regulators, which eventually replaced ancestral cyclins, transcription factors, and inhibitors in Dikarya.
Basal fungi and 'Zygomycota' contain hybrid networks comprised of both ancestral and fungal specific cell cycle regulators. Check marks indicate the presence of at least one member of a protein …
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Figure 3—source data 1
Complete set of fungal SBF/MBF transcription factors for phylogenetic analysis.
These files contain the protein sequences used to create molecular phylogeny in Figure 3—figure supplement 2.
- https://doi.org/10.7554/eLife.09492.017
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Figure 3—source data 2
Complete set of fungal SBF/MBF and APSES transcription factors for phylogenetic analysis.
These files contain the protein sequences used to create molecular phylogeny in Figure 3—figure supplement 3.
- https://doi.org/10.7554/eLife.09492.018
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Figure 3—source data 3
Complete set of fungal Whi5/Nrm1 inhibitors for phylogenetic analysis.
These files contain the protein sequences used to create molecular phylogeny in Figure 3—figure supplement 4.
- https://doi.org/10.7554/eLife.09492.019
Figure 3—figure supplement 1
Comparative genomic data of G1/S regulators across fungi.
Grey rows list the sub-family gene names in S. cerevisiae, S. pombe, and H. sapiens. Protein sequences listed in this table, which were used to create new molecular phylogenies not shown in Figure 2,…
Figure 3—figure supplement 2
Phylogeny of fungal SBF/MBF transcription factors.
SBF and MBF are transcription factors that regulate G1/S transcription in budding and fission yeast. To detect SMRC (Swi4/6 Mbp1 Res1/2 Cdc10) across fungi, we built a sensitive profile-HMM …
Figure 3—figure supplement 3
Phylogeny of fungal SBF/MBF and APSES transcription factors.
SBF/MBF and APSES transcription factors (Asm1, Phd1, Sok2, Efg1, StuA) share a common DNA-binding domain (KilA-N), which is derived from DNA viruses. During our search for SBF and APSES homologs, we …
Figure 3—figure supplement 4
Phylogeny of fungal Whi5/Nrm1 inhibitors.
WHI5 and NRM1 are a yeast-specific protein family that has been identified and functionally characterized across S. cerevisiae, C. albicans, and S. pombe. Both WHI5 and NRM1 are fast evolving …
Figure 4
SBF and E2F HMM models detect different sequences.
We used the Pfam HMMER model of the E2F/DP DNA-binding domain (E2F_TDP.hmm) and SBF DNA-binding domain (KilA-N.hmm). Every protein in the query genome (listed at top) was scored using hmmsearch with …
Figure 5
E2F and SBF show incongruences in sequence, structure, and mode of DNA binding.
(A) Although both proteins share a winged helix-turn-helix (wHTH) domain, the E2F/DP and SBF/MBF superfamilies do not exhibit significant sequence identity or structural similarity to suggest a …
Figure 6
Viral origin of yeast cell cycle transcription factor SBF.
Maximum likelihood unrooted phylogenetic tree depicting relationships of fungal SBF-family proteins, KilA-N domains in prokaryotic and eukaryotic DNA viruses. The original dataset was manually …
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Figure 6—source data 1
Reduced set of KilA-N domains for phylogenetic analysis.
These files contain the protein sequences used to create molecular phylogeny in Figure 5.
- https://doi.org/10.7554/eLife.09492.027
Figure 7
Yeast cell cycle transcription factor SBF can regulate cell cycle-dependent transcription via E2F binding sites in vivo.
(A) Phylogenetic tree of animals, chytrids, yeast labelled with E2F, SBF or both transcription factors (TF) if present in their genomes. The known DNA-binding motifs of animal E2F (E2F1) and yeast …
Figure 8 with 2 supplements
High-throughput DNA binding data for yeast SBF and human E2F shows that SBF and E2F can bind shared and distinct DNA-binding sites.
Plot of in vitro protein binding microarray 8-mer E-scores for Homo sapiens E2F1 (Afek et al., 2014) versus S. cerevisiae SBF protein Swi4 (Badis et al., 2008). All 8-mer motifs colored (E-score > …
Figure 8—figure supplement 1
Bioinformatic scan of E2F-regulated human promoters suggests possible regulation by SBF.
E2F1 (top) and SBF (bottom) PBM motifs were used to scan the proximal (1000 bp) promoters of E2F-regulated promoters (CCNE1, E2F1, and EZH2). Promoter regions with a significant hit (8-mer E-score > …
Figure 8—figure supplement 2
Many E2F-regulated genes in humans could be bound by SBF.
Summary of E2F-only regions (blue), SBF-only regions (purple), and E2F and SBF co-regulated regions (yellow) for a set of 290 E2F-regulated promoters.
Figure 9
Punctuated evolution of a conserved regulatory network.
Evolution can replace components in an essential pathway by proceeding through a hybrid intermediate. Once established, the hybrid network can evolve dramatically and lose previously essential …
Additional files
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Supplementary file 1
(A) List of eukaryotic genomes. We downloaded and analyzed the following annotated genomes using the 'best' filtered protein sets when available. We gratefully acknowledge the Broad Institute, the DOE Joint Genome Institute, Génolevures, PlantGDB, SaccharomycesGD, AshbyaGD, DictyBase, JCV Institute, Sanger Institute, TetrahymenaGD, PythiumGD, AmoebaDB, NannochloroposisGD, OrcAE, TriTryDB, GiardiaDB, TrichDB, CyanophoraDB, and CyanidioschizonDB for making their annotated genomes publicly available. We especially thank D. Armaleo, I. Grigoriev, T. Jeffries, J. Spatafora, S. Baker, J. Collier, and T. Mock for allowing us to use their unpublished data. (B) Plasmids. (C) Strains. All yeast strains were derived from W303 and constructed using standard methods.
- https://doi.org/10.7554/eLife.09492.033
