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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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Phylogeny of Runx (A) and CBFβ (B) proteins. In both cases, maximum likelihood trees were constructed using the program PhyML. In the case of Runx, likelihoods were calculated using the Rt-REV amino acid substitution matrix [83]. In the case of CBFβ, likelihoods were calculated using the JTT amino acid substitution matrix. Separate neighbor-joining analyses using the JTT distance matrix were also performed for each data set (not shown). The bars and icons indicate the locations of the taxonomic groupings on each tree with the deuterostome and protostome groups marked with filled and empty circles respectively. Both trees are rooted between the sponge sequences and the eumetazoan sequences. The length of each horizontal branch is proportional to the number of amino acid substitutions that have occurred along that branch (scale at lower part of each panel). The first and second numbers at each node indicate the percentage of 1,000 bootstrap replicates in which the given clade is recovered with maximum likelihood and neighbor-joining analyses, respectively. Nodes which failed to receive at least 40% bootstrap support in one of the analyses are not labeled. The sources of the sequences and the abbreviations for taxa are provided in Additional files 9 and 10.
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Figure 4: Phylogeny of Runx (A) and CBFβ (B) proteins. In both cases, maximum likelihood trees were constructed using the program PhyML. In the case of Runx, likelihoods were calculated using the Rt-REV amino acid substitution matrix [83]. In the case of CBFβ, likelihoods were calculated using the JTT amino acid substitution matrix. Separate neighbor-joining analyses using the JTT distance matrix were also performed for each data set (not shown). The bars and icons indicate the locations of the taxonomic groupings on each tree with the deuterostome and protostome groups marked with filled and empty circles respectively. Both trees are rooted between the sponge sequences and the eumetazoan sequences. The length of each horizontal branch is proportional to the number of amino acid substitutions that have occurred along that branch (scale at lower part of each panel). The first and second numbers at each node indicate the percentage of 1,000 bootstrap replicates in which the given clade is recovered with maximum likelihood and neighbor-joining analyses, respectively. Nodes which failed to receive at least 40% bootstrap support in one of the analyses are not labeled. The sources of the sequences and the abbreviations for taxa are provided in Additional files 9 and 10.

Mentions: Figure 4A depicts a phylogeny of Runx proteins from sponges, cnidarians, chordates, echinoderms, and arthropods. Sequences from the nematodes C. elegans, C. brigsae, and D. coronatus were excluded from this analysis as they are highly divergent from the other metazoan Runx proteins, and their inclusion would tend to cause long-branch attraction artifacts. An analysis including the nematode species is presented in Additional file 6 (see Additional file 9 for taxon IDs). The tree is rooted using the two sponge sequences. Consistent with the prevailing view of organismal phylogeny, this gene tree groups the two sponge sequences, the eighteen triploblast sequences, the six chordate sequences, the two urchin sequences, and the ten arthropod sequences into mutually exclusive clades, with each clade receiving bootstrap support > 75%. The Runx sequences do not recover a monophyletic Deuterostomia as the two sea urchin sequences (Strongylocentrotus and Heliocidaris) group more closely with insects than with chordates (although the bootstrap support for this grouping is relatively low). Neither does the Runx tree support cnidarian monophyly, as the sea anemone and hydra sequences appear as successive outgroups at the base of the triploblast clade. Interestingly, this tree implies that the cnidarian proteins have evolved relatively slowly. In particular, the sea anemone Runx appears to have undergone the least amount of evolutionary change of any taxon since the time of the sponge-triploblast ancestor. The anemone may therefore represent our best source of information regarding the ancestral Runx protein. As the human Runx paralogs (Runx1–3) and the insect Runx paralogs (e.g., Drosophila Lozenge, Runt, RuntA, and RuntB) fall into distinct and well supported clades, this tree implies that the ancestral Runx gene underwent independent gene duplication in the deuterostome and protostome lineages.


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)

Phylogeny of Runx (A) and CBFβ (B) proteins. In both cases, maximum likelihood trees were constructed using the program PhyML. In the case of Runx, likelihoods were calculated using the Rt-REV amino acid substitution matrix [83]. In the case of CBFβ, likelihoods were calculated using the JTT amino acid substitution matrix. Separate neighbor-joining analyses using the JTT distance matrix were also performed for each data set (not shown). The bars and icons indicate the locations of the taxonomic groupings on each tree with the deuterostome and protostome groups marked with filled and empty circles respectively. Both trees are rooted between the sponge sequences and the eumetazoan sequences. The length of each horizontal branch is proportional to the number of amino acid substitutions that have occurred along that branch (scale at lower part of each panel). The first and second numbers at each node indicate the percentage of 1,000 bootstrap replicates in which the given clade is recovered with maximum likelihood and neighbor-joining analyses, respectively. Nodes which failed to receive at least 40% bootstrap support in one of the analyses are not labeled. The sources of the sequences and the abbreviations for taxa are provided in Additional files 9 and 10.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Phylogeny of Runx (A) and CBFβ (B) proteins. In both cases, maximum likelihood trees were constructed using the program PhyML. In the case of Runx, likelihoods were calculated using the Rt-REV amino acid substitution matrix [83]. In the case of CBFβ, likelihoods were calculated using the JTT amino acid substitution matrix. Separate neighbor-joining analyses using the JTT distance matrix were also performed for each data set (not shown). The bars and icons indicate the locations of the taxonomic groupings on each tree with the deuterostome and protostome groups marked with filled and empty circles respectively. Both trees are rooted between the sponge sequences and the eumetazoan sequences. The length of each horizontal branch is proportional to the number of amino acid substitutions that have occurred along that branch (scale at lower part of each panel). The first and second numbers at each node indicate the percentage of 1,000 bootstrap replicates in which the given clade is recovered with maximum likelihood and neighbor-joining analyses, respectively. Nodes which failed to receive at least 40% bootstrap support in one of the analyses are not labeled. The sources of the sequences and the abbreviations for taxa are provided in Additional files 9 and 10.
Mentions: Figure 4A depicts a phylogeny of Runx proteins from sponges, cnidarians, chordates, echinoderms, and arthropods. Sequences from the nematodes C. elegans, C. brigsae, and D. coronatus were excluded from this analysis as they are highly divergent from the other metazoan Runx proteins, and their inclusion would tend to cause long-branch attraction artifacts. An analysis including the nematode species is presented in Additional file 6 (see Additional file 9 for taxon IDs). The tree is rooted using the two sponge sequences. Consistent with the prevailing view of organismal phylogeny, this gene tree groups the two sponge sequences, the eighteen triploblast sequences, the six chordate sequences, the two urchin sequences, and the ten arthropod sequences into mutually exclusive clades, with each clade receiving bootstrap support > 75%. The Runx sequences do not recover a monophyletic Deuterostomia as the two sea urchin sequences (Strongylocentrotus and Heliocidaris) group more closely with insects than with chordates (although the bootstrap support for this grouping is relatively low). Neither does the Runx tree support cnidarian monophyly, as the sea anemone and hydra sequences appear as successive outgroups at the base of the triploblast clade. Interestingly, this tree implies that the cnidarian proteins have evolved relatively slowly. In particular, the sea anemone Runx appears to have undergone the least amount of evolutionary change of any taxon since the time of the sponge-triploblast ancestor. The anemone may therefore represent our best source of information regarding the ancestral Runx protein. As the human Runx paralogs (Runx1–3) and the insect Runx paralogs (e.g., Drosophila Lozenge, Runt, RuntA, and RuntB) fall into distinct and well supported clades, this tree implies that the ancestral Runx gene underwent independent gene duplication in the deuterostome and protostome lineages.

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