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The evolutionary origin of the Runx/CBFbeta transcription factors--studies of the most basal metazoans.

Sullivan JC, Sher D, Eisenstein M, Shigesada K, Reitzel AM, Marlow H, Levanon D, Groner Y, Finnerty JR, Gat U - BMC Evol. Biol. (2008)

Bottom Line: Comparative structural modeling indicates that the Runx-CBFbeta-DNA complex from most cnidarians and sponges is highly similar to that found in humans, with changes in the residues involved in Runx-CBFbeta dimerization in either of the proteins mirrored by compensatory changes in the binding partner.These results reveal that Runx and CBFbeta likely functioned together to regulate transcription in the common ancestor of all metazoans, and the structure of the Runx-CBFbeta-DNA complex has remained extremely conserved since the human-sponge divergence.The expression data suggest a hypothesis that these genes may have played a role in nerve cell differentiation or maintenance in the common ancestor of cnidarians and bilaterians.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biology, Boston University, 5 Cummington St, Boston, MA 02215, USA. jamescsullivan@gmail.com

ABSTRACT

Background: Members of the Runx family of transcriptional regulators, which bind DNA as heterodimers with CBFbeta, are known to play critical roles in embryonic development in many triploblastic animals such as mammals and insects. They are known to regulate basic developmental processes such as cell fate determination and cellular potency in multiple stem-cell types, including the sensory nerve cell progenitors of ganglia in mammals.

Results: In this study, we detect and characterize the hitherto unexplored Runx/CBFbeta genes of cnidarians and sponges, two basal animal lineages that are well known for their extensive regenerative capacity. Comparative structural modeling indicates that the Runx-CBFbeta-DNA complex from most cnidarians and sponges is highly similar to that found in humans, with changes in the residues involved in Runx-CBFbeta dimerization in either of the proteins mirrored by compensatory changes in the binding partner. In situ hybridization studies reveal that Nematostella Runx and CBFbeta are expressed predominantly in small isolated foci at the base of the ectoderm of the tentacles in adult animals, possibly representing neurons or their progenitors.

Conclusion: These results reveal that Runx and CBFbeta likely functioned together to regulate transcription in the common ancestor of all metazoans, and the structure of the Runx-CBFbeta-DNA complex has remained extremely conserved since the human-sponge divergence. The expression data suggest a hypothesis that these genes may have played a role in nerve cell differentiation or maintenance in the common ancestor of cnidarians and bilaterians.

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Co-evolution of Runx and CBFβ proteins. A) We generated the accepted organismal phylogeny relating 11 taxa for which both Runx and CBFβ sequences are available. We then inferred the evolutionary change in Runx (blue) and CBFβ (green) along each branch of this phylogeny by using the JTT matrix to calculate patristic distances. B) For each node on the tree, the evolutionary change in CBFβ and GAPDH were plotted against the evolutionary change in Runx. The regression reveals a significant and strong correlation between the evolutionary change in Runx and CBFβ (represented by squares and solid line; R2 = 0.83, F1,17 = 85.11, p < 0.0001) but not between Runx and GAPDH (circles and dashed line). The outliers (the circle and square with a Runx branch length of ~0.3) represent the divergence between the protostome ancestor and the common Caenorhabditis ancestor (see panel A). Both Runx (branch length = ~0.3) and CBFβ (branch length = ~0.44) diverged rapidly within this lineage, while GAPDH continued to evolve more slowly (equivalent branch length in GAPDH tree = ~0.05).
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Figure 5: Co-evolution of Runx and CBFβ proteins. A) We generated the accepted organismal phylogeny relating 11 taxa for which both Runx and CBFβ sequences are available. We then inferred the evolutionary change in Runx (blue) and CBFβ (green) along each branch of this phylogeny by using the JTT matrix to calculate patristic distances. B) For each node on the tree, the evolutionary change in CBFβ and GAPDH were plotted against the evolutionary change in Runx. The regression reveals a significant and strong correlation between the evolutionary change in Runx and CBFβ (represented by squares and solid line; R2 = 0.83, F1,17 = 85.11, p < 0.0001) but not between Runx and GAPDH (circles and dashed line). The outliers (the circle and square with a Runx branch length of ~0.3) represent the divergence between the protostome ancestor and the common Caenorhabditis ancestor (see panel A). Both Runx (branch length = ~0.3) and CBFβ (branch length = ~0.44) diverged rapidly within this lineage, while GAPDH continued to evolve more slowly (equivalent branch length in GAPDH tree = ~0.05).

Mentions: In addition to the apparent reciprocity of amino acid changes that we have observed in the interacting portions of Runx and CBFβ, the anomalous position of the sea urchin sequences on both the Runx and CBFβ trees could be another reflection of co-evolution between these proteins. To explore this hypothesis further, we employed a variation on the protein co-evolution test proposed by Sato and coworkers [52] (Figure 5). When each of the phylogenies described above is limited to only those 11 taxa contained in both phylogenies, and the tree topologies are constrained to the accepted organismal phylogeny (Figure. 5A), the resultant branch lengths on the two trees are significantly and strongly correlated (Figure 5B, R2 = 0.83; Linear Least Regression test for significance: F1,17 = 85.11, p < 0.0001). In contrast, the branch lengths from a glyceraldehyde-phosphate-dehydrogenase phylogeny, which is a "house-keeping" gene serving as a control, are not correlated with the Runx branch lengths (F1,17 = 2.73, p = 0.1167) and only weakly correlated with the branch lengths from the CBFβ phylogeny (F1,17 = 9.31, p = 0.0072, R2= 0.35).


The evolutionary origin of the Runx/CBFbeta transcription factors--studies of the most basal metazoans.

Sullivan JC, Sher D, Eisenstein M, Shigesada K, Reitzel AM, Marlow H, Levanon D, Groner Y, Finnerty JR, Gat U - BMC Evol. Biol. (2008)

Co-evolution of Runx and CBFβ proteins. A) We generated the accepted organismal phylogeny relating 11 taxa for which both Runx and CBFβ sequences are available. We then inferred the evolutionary change in Runx (blue) and CBFβ (green) along each branch of this phylogeny by using the JTT matrix to calculate patristic distances. B) For each node on the tree, the evolutionary change in CBFβ and GAPDH were plotted against the evolutionary change in Runx. The regression reveals a significant and strong correlation between the evolutionary change in Runx and CBFβ (represented by squares and solid line; R2 = 0.83, F1,17 = 85.11, p < 0.0001) but not between Runx and GAPDH (circles and dashed line). The outliers (the circle and square with a Runx branch length of ~0.3) represent the divergence between the protostome ancestor and the common Caenorhabditis ancestor (see panel A). Both Runx (branch length = ~0.3) and CBFβ (branch length = ~0.44) diverged rapidly within this lineage, while GAPDH continued to evolve more slowly (equivalent branch length in GAPDH tree = ~0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2527000&req=5

Figure 5: Co-evolution of Runx and CBFβ proteins. A) We generated the accepted organismal phylogeny relating 11 taxa for which both Runx and CBFβ sequences are available. We then inferred the evolutionary change in Runx (blue) and CBFβ (green) along each branch of this phylogeny by using the JTT matrix to calculate patristic distances. B) For each node on the tree, the evolutionary change in CBFβ and GAPDH were plotted against the evolutionary change in Runx. The regression reveals a significant and strong correlation between the evolutionary change in Runx and CBFβ (represented by squares and solid line; R2 = 0.83, F1,17 = 85.11, p < 0.0001) but not between Runx and GAPDH (circles and dashed line). The outliers (the circle and square with a Runx branch length of ~0.3) represent the divergence between the protostome ancestor and the common Caenorhabditis ancestor (see panel A). Both Runx (branch length = ~0.3) and CBFβ (branch length = ~0.44) diverged rapidly within this lineage, while GAPDH continued to evolve more slowly (equivalent branch length in GAPDH tree = ~0.05).
Mentions: In addition to the apparent reciprocity of amino acid changes that we have observed in the interacting portions of Runx and CBFβ, the anomalous position of the sea urchin sequences on both the Runx and CBFβ trees could be another reflection of co-evolution between these proteins. To explore this hypothesis further, we employed a variation on the protein co-evolution test proposed by Sato and coworkers [52] (Figure 5). When each of the phylogenies described above is limited to only those 11 taxa contained in both phylogenies, and the tree topologies are constrained to the accepted organismal phylogeny (Figure. 5A), the resultant branch lengths on the two trees are significantly and strongly correlated (Figure 5B, R2 = 0.83; Linear Least Regression test for significance: F1,17 = 85.11, p < 0.0001). In contrast, the branch lengths from a glyceraldehyde-phosphate-dehydrogenase phylogeny, which is a "house-keeping" gene serving as a control, are not correlated with the Runx branch lengths (F1,17 = 2.73, p = 0.1167) and only weakly correlated with the branch lengths from the CBFβ phylogeny (F1,17 = 9.31, p = 0.0072, R2= 0.35).

Bottom Line: Comparative structural modeling indicates that the Runx-CBFbeta-DNA complex from most cnidarians and sponges is highly similar to that found in humans, with changes in the residues involved in Runx-CBFbeta dimerization in either of the proteins mirrored by compensatory changes in the binding partner.These results reveal that Runx and CBFbeta likely functioned together to regulate transcription in the common ancestor of all metazoans, and the structure of the Runx-CBFbeta-DNA complex has remained extremely conserved since the human-sponge divergence.The expression data suggest a hypothesis that these genes may have played a role in nerve cell differentiation or maintenance in the common ancestor of cnidarians and bilaterians.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biology, Boston University, 5 Cummington St, Boston, MA 02215, USA. jamescsullivan@gmail.com

ABSTRACT

Background: Members of the Runx family of transcriptional regulators, which bind DNA as heterodimers with CBFbeta, are known to play critical roles in embryonic development in many triploblastic animals such as mammals and insects. They are known to regulate basic developmental processes such as cell fate determination and cellular potency in multiple stem-cell types, including the sensory nerve cell progenitors of ganglia in mammals.

Results: In this study, we detect and characterize the hitherto unexplored Runx/CBFbeta genes of cnidarians and sponges, two basal animal lineages that are well known for their extensive regenerative capacity. Comparative structural modeling indicates that the Runx-CBFbeta-DNA complex from most cnidarians and sponges is highly similar to that found in humans, with changes in the residues involved in Runx-CBFbeta dimerization in either of the proteins mirrored by compensatory changes in the binding partner. In situ hybridization studies reveal that Nematostella Runx and CBFbeta are expressed predominantly in small isolated foci at the base of the ectoderm of the tentacles in adult animals, possibly representing neurons or their progenitors.

Conclusion: These results reveal that Runx and CBFbeta likely functioned together to regulate transcription in the common ancestor of all metazoans, and the structure of the Runx-CBFbeta-DNA complex has remained extremely conserved since the human-sponge divergence. The expression data suggest a hypothesis that these genes may have played a role in nerve cell differentiation or maintenance in the common ancestor of cnidarians and bilaterians.

Show MeSH
Related in: MedlinePlus