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Evolution of the holozoan ribosome biogenesis regulon.

Brown SJ, Cole MD, Erives AJ - BMC Genomics (2008)

Bottom Line: These results show that this mode of regulation, characterized by an E(CG)-bearing core-promoter, is specific to almost all of the known genes involved in ribosome biogenesis in these genomes.Furthermore, a detailed analysis of 10 fungal genomes shows that this holozoan signature in RiBi genes is not found in hemiascomycete fungi, which evolved their own unique regulatory signature for the RiBi regulon.Furthermore, by comparing divergent bHLH repertoires, we conclude that regulation by Myc but not by other bHLH genes is responsible for the evolutionary maintenance of E(CG) sites across the RiBi suite of genes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Genetics, Dartmouth Medical School, 1 Medical Center Drive, Lebanon, NH 03756, USA. seth.brown@dartmouth.edu

ABSTRACT

Background: The ribosome biogenesis (RiBi) genes encode a highly-conserved eukaryotic set of nucleolar proteins involved in rRNA transcription, assembly, processing, and export from the nucleus. While the mode of regulation of this suite of genes has been studied in the yeast, Saccharomyces cerevisiae, how this gene set is coordinately regulated in the larger and more complex metazoan genomes is not understood.

Results: Here we present genome-wide analyses indicating that a distinct mode of RiBi regulation co-evolved with the E(CG)-binding, Myc:Max bHLH heterodimer complex in a stem-holozoan, the ancestor of both Metazoa and Choanoflagellata, the protozoan group most closely related to animals. These results show that this mode of regulation, characterized by an E(CG)-bearing core-promoter, is specific to almost all of the known genes involved in ribosome biogenesis in these genomes. Interestingly, this holozoan RiBi promoter signature is absent in nematode genomes, which have not only secondarily lost Myc but are marked by invariant cell lineages typically producing small body plans of 1000 somatic cells. Furthermore, a detailed analysis of 10 fungal genomes shows that this holozoan signature in RiBi genes is not found in hemiascomycete fungi, which evolved their own unique regulatory signature for the RiBi regulon.

Conclusion: These results indicate that a Myc regulon, which is activated in proliferating cells during normal development as well as during tumor progression, has primordial roots in the evolution of an inducible growth regime in a protozoan ancestor of animals. Furthermore, by comparing divergent bHLH repertoires, we conclude that regulation by Myc but not by other bHLH genes is responsible for the evolutionary maintenance of E(CG) sites across the RiBi suite of genes.

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The RiBi-E(CG) regulon occurs only in Myc-bearing holozoan genomes. (A) Specific amino acid residues in holozoan MAX (red), MAD (blue), MNT (pink), and MYC (green) allow identification among the MYC/MAX superfamily bHLH genes (common superfamily residues in yellow and underlined). Only three bHLH genes were found in the choanoflagellate genome of Monosiga brevicollis: Mb-MYC, MbMAX and MbMUSH, corresponding to Myc and Max orthologs, and a distant MITF/USF/SREBP homolog (not shown). No Myc and Max orthologs were found outside of Holozoa. The predicted amino acid sequences of the bHLH regions of the M. brevicollis Myc/Max family of genes are shown aligned to Drosophila, Caenorhabditis, and Nematostella orthologs. (B) The presence of Myc (green filled boxes) is correlated with multiple genomes possessing the E(CG)-RiBi signature (green filled boxes). Other bHLH genes in the Myc superfamily (Max, Mad, Mnt; gray filled boxes) are either not necessary (Mad or Mnt) or insufficient (Max) to explain the occurrence of E(CG) sites in the RiBi regulon. "X" boxes indicate absence of a gene or E(CG) signature as indicated.
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Figure 3: The RiBi-E(CG) regulon occurs only in Myc-bearing holozoan genomes. (A) Specific amino acid residues in holozoan MAX (red), MAD (blue), MNT (pink), and MYC (green) allow identification among the MYC/MAX superfamily bHLH genes (common superfamily residues in yellow and underlined). Only three bHLH genes were found in the choanoflagellate genome of Monosiga brevicollis: Mb-MYC, MbMAX and MbMUSH, corresponding to Myc and Max orthologs, and a distant MITF/USF/SREBP homolog (not shown). No Myc and Max orthologs were found outside of Holozoa. The predicted amino acid sequences of the bHLH regions of the M. brevicollis Myc/Max family of genes are shown aligned to Drosophila, Caenorhabditis, and Nematostella orthologs. (B) The presence of Myc (green filled boxes) is correlated with multiple genomes possessing the E(CG)-RiBi signature (green filled boxes). Other bHLH genes in the Myc superfamily (Max, Mad, Mnt; gray filled boxes) are either not necessary (Mad or Mnt) or insufficient (Max) to explain the occurrence of E(CG) sites in the RiBi regulon. "X" boxes indicate absence of a gene or E(CG) signature as indicated.

Mentions: To test whether components of the fly RiBi regulon are conserved outside of Bilateria, we analyzed the presence of the E(CG) signature in the RiBi orthologous cohort in the genomes of more distantly-related organisms (Figs. 2 and 3). For a metazoan outgroup to Bilateria, we used the cnidarian genome of Nematostella vectensis [27]. For a holozoan outgroup to Metazoa, we used the choanoflagellate genome of Monosiga brevicollis [28]. For an opisthokont out-group to Holozoa, we used the baker's yeast genome of Saccharomyces cerevisiae.


Evolution of the holozoan ribosome biogenesis regulon.

Brown SJ, Cole MD, Erives AJ - BMC Genomics (2008)

The RiBi-E(CG) regulon occurs only in Myc-bearing holozoan genomes. (A) Specific amino acid residues in holozoan MAX (red), MAD (blue), MNT (pink), and MYC (green) allow identification among the MYC/MAX superfamily bHLH genes (common superfamily residues in yellow and underlined). Only three bHLH genes were found in the choanoflagellate genome of Monosiga brevicollis: Mb-MYC, MbMAX and MbMUSH, corresponding to Myc and Max orthologs, and a distant MITF/USF/SREBP homolog (not shown). No Myc and Max orthologs were found outside of Holozoa. The predicted amino acid sequences of the bHLH regions of the M. brevicollis Myc/Max family of genes are shown aligned to Drosophila, Caenorhabditis, and Nematostella orthologs. (B) The presence of Myc (green filled boxes) is correlated with multiple genomes possessing the E(CG)-RiBi signature (green filled boxes). Other bHLH genes in the Myc superfamily (Max, Mad, Mnt; gray filled boxes) are either not necessary (Mad or Mnt) or insufficient (Max) to explain the occurrence of E(CG) sites in the RiBi regulon. "X" boxes indicate absence of a gene or E(CG) signature as indicated.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2570694&req=5

Figure 3: The RiBi-E(CG) regulon occurs only in Myc-bearing holozoan genomes. (A) Specific amino acid residues in holozoan MAX (red), MAD (blue), MNT (pink), and MYC (green) allow identification among the MYC/MAX superfamily bHLH genes (common superfamily residues in yellow and underlined). Only three bHLH genes were found in the choanoflagellate genome of Monosiga brevicollis: Mb-MYC, MbMAX and MbMUSH, corresponding to Myc and Max orthologs, and a distant MITF/USF/SREBP homolog (not shown). No Myc and Max orthologs were found outside of Holozoa. The predicted amino acid sequences of the bHLH regions of the M. brevicollis Myc/Max family of genes are shown aligned to Drosophila, Caenorhabditis, and Nematostella orthologs. (B) The presence of Myc (green filled boxes) is correlated with multiple genomes possessing the E(CG)-RiBi signature (green filled boxes). Other bHLH genes in the Myc superfamily (Max, Mad, Mnt; gray filled boxes) are either not necessary (Mad or Mnt) or insufficient (Max) to explain the occurrence of E(CG) sites in the RiBi regulon. "X" boxes indicate absence of a gene or E(CG) signature as indicated.
Mentions: To test whether components of the fly RiBi regulon are conserved outside of Bilateria, we analyzed the presence of the E(CG) signature in the RiBi orthologous cohort in the genomes of more distantly-related organisms (Figs. 2 and 3). For a metazoan outgroup to Bilateria, we used the cnidarian genome of Nematostella vectensis [27]. For a holozoan outgroup to Metazoa, we used the choanoflagellate genome of Monosiga brevicollis [28]. For an opisthokont out-group to Holozoa, we used the baker's yeast genome of Saccharomyces cerevisiae.

Bottom Line: These results show that this mode of regulation, characterized by an E(CG)-bearing core-promoter, is specific to almost all of the known genes involved in ribosome biogenesis in these genomes.Furthermore, a detailed analysis of 10 fungal genomes shows that this holozoan signature in RiBi genes is not found in hemiascomycete fungi, which evolved their own unique regulatory signature for the RiBi regulon.Furthermore, by comparing divergent bHLH repertoires, we conclude that regulation by Myc but not by other bHLH genes is responsible for the evolutionary maintenance of E(CG) sites across the RiBi suite of genes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Genetics, Dartmouth Medical School, 1 Medical Center Drive, Lebanon, NH 03756, USA. seth.brown@dartmouth.edu

ABSTRACT

Background: The ribosome biogenesis (RiBi) genes encode a highly-conserved eukaryotic set of nucleolar proteins involved in rRNA transcription, assembly, processing, and export from the nucleus. While the mode of regulation of this suite of genes has been studied in the yeast, Saccharomyces cerevisiae, how this gene set is coordinately regulated in the larger and more complex metazoan genomes is not understood.

Results: Here we present genome-wide analyses indicating that a distinct mode of RiBi regulation co-evolved with the E(CG)-binding, Myc:Max bHLH heterodimer complex in a stem-holozoan, the ancestor of both Metazoa and Choanoflagellata, the protozoan group most closely related to animals. These results show that this mode of regulation, characterized by an E(CG)-bearing core-promoter, is specific to almost all of the known genes involved in ribosome biogenesis in these genomes. Interestingly, this holozoan RiBi promoter signature is absent in nematode genomes, which have not only secondarily lost Myc but are marked by invariant cell lineages typically producing small body plans of 1000 somatic cells. Furthermore, a detailed analysis of 10 fungal genomes shows that this holozoan signature in RiBi genes is not found in hemiascomycete fungi, which evolved their own unique regulatory signature for the RiBi regulon.

Conclusion: These results indicate that a Myc regulon, which is activated in proliferating cells during normal development as well as during tumor progression, has primordial roots in the evolution of an inducible growth regime in a protozoan ancestor of animals. Furthermore, by comparing divergent bHLH repertoires, we conclude that regulation by Myc but not by other bHLH genes is responsible for the evolutionary maintenance of E(CG) sites across the RiBi suite of genes.

Show MeSH
Related in: MedlinePlus