Nuclear receptors from the ctenophore Mnemiopsis leidyi lack a zinc-finger DNA-binding domain: lineage-specific loss or ancestral condition in the emergence of the nuclear receptor superfamily? - PubMed
- ️Sat Jan 01 2011
Nuclear receptors from the ctenophore Mnemiopsis leidyi lack a zinc-finger DNA-binding domain: lineage-specific loss or ancestral condition in the emergence of the nuclear receptor superfamily?
Adam M Reitzel et al. Evodevo. 2011.
Abstract
Background: Nuclear receptors (NRs) are an ancient superfamily of metazoan transcription factors that play critical roles in regulation of reproduction, development, and energetic homeostasis. Although the evolutionary relationships among NRs are well-described in two prominent clades of animals (deuterostomes and protostomes), comparatively little information has been reported on the diversity of NRs in early diverging metazoans. Here, we identified NRs from the phylum Ctenophora and used a phylogenomic approach to explore the emergence of the NR superfamily in the animal kingdom. In addition, to gain insight into conserved or novel functions, we examined NR expression during ctenophore development.
Results: We report the first described NRs from the phylum Ctenophora: two from Mnemiopsis leidyi and one from Pleurobrachia pileus. All ctenophore NRs contained a ligand-binding domain and grouped with NRs from the subfamily NR2A (HNF4). Surprisingly, all the ctenophore NRs lacked the highly conserved DNA-binding domain (DBD). NRs from Mnemiopsis were expressed in different regions of developing ctenophores. One was broadly expressed in the endoderm during gastrulation. The second was initially expressed in the ectoderm during gastrulation, in regions corresponding to the future tentacles; subsequent expression was restricted to the apical organ. Phylogenetic analyses of NRs from ctenophores, sponges, cnidarians, and a placozoan support the hypothesis that expansion of the superfamily occurred in a step-wise fashion, with initial radiations in NR family 2, followed by representatives of NR families 3, 6, and 1/4 originating prior to the appearance of the bilaterian ancestor.
Conclusions: Our study provides the first description of NRs from ctenophores, including the full complement from Mnemiopsis. Ctenophores have the least diverse NR complement of any animal phylum with representatives that cluster with only one subfamily (NR2A). Ctenophores and sponges have a similarly restricted NR complement supporting the hypothesis that the original NR was HNF4-like and that these lineages are the first two branches from the animal tree. The absence of a zinc-finger DNA-binding domain in the two ctenophore species suggests two hypotheses: this domain may have been secondarily lost within the ctenophore lineage or, if ctenophores are the first branch off the animal tree, the original NR may have lacked the canonical DBD. Phylogenomic analyses and categorization of NRs from all four early diverging animal phyla compared with the complement from bilaterians suggest the rate of NR diversification prior to the cnidarian-bilaterian split was relatively modest, with independent radiations of several NR subfamilies within the cnidarian lineage.
Figures

Nuclear receptors from the ctenophores Mnemiopsis leidyi and Pleurobrachia pileus. (A) Intron-exon structure of the two nuclear receptors from Mnemiopsis. MlNR2 is a single exon gene. MlNR1 has a more complex intron-exon structure with eight exons, seven of which code for the inferred open-reading frame. (B) Alignment of the amino-terminal region of the ctenophore NRs with the DNA-binding domains of NRs from two sponges (Amphimedon queenslandica (Aq) and Suberites domuncula (Sd)), and HNF4 from Trichoplax adhaerens (Ta), Nematostella vectensis (Nv), Drosophila melanogaster (Dm), and Homo sapiens (Hs). The ctenophore proteins align poorly, including an absence of the conserved cysteines (indicated by black circles), and an optimized alignment contains insertions and deletions relative to the DBD of other animals. (C) Alignment of the ligand-binding domain from the same taxa as in (B). The ctenophore LBD is well-conserved, particularly the nuclear receptor signature motif spanning helix 3 and 4 (boxed).

Expression of MlNR1 (A-J) and MlNR2 (K-N) in embryos and juveniles of Mnemiopsis. A-E show aboral views of MlNR1, with F-J showing lateral views of the corresponding embryo. (A-B, F-G) MlNR1 expression in ectoderm of the future tentacle bulb (tb) in the gastrula and late gastrula stage. (C-D, H-I) Expression continues in ectoderm of future tentacle bulb as well as in additional domain along the sagittal plane (arrowhead) in the postgastrula. (E, J) MlNR1 expression is restricted to the apical organ (ao) in the cydippid stage. (K-N) MlNR2 is broadly detected in the endoderm (en) in developmental stages after gastrulation and in the cydippid. It is only in the most aboral part of the pharynx (ph). There are also additional domains in the ectoderm (white arrowheads).

Maximum likelihood tree of nuclear receptor superfamily. Clades are annotated to family and subfamily based on current nomenclature for the NR superfamily [8]. Tree was rooted with the cluster containing the ctenophore sequences plus HNF4 from diverse animals. Values above nodes indicate percent of 1,000 bootstraps. Bootstrap values below 40 were removed.

Evolutionary diversification of the NR superfamily in animals. At left is a cartoon of the metazoan tree showing the evolutionary relationships between ctenophores, sponges, placozoan, cnidarians, and bilaterians (that is, protostomes and deuterostomes). Due to current controversy about the branching order of the early diverging metazoans (see main text), the placement of lineages differs depending on particular analyses and thus an inference for the timing of origin and lineage-specific loss of particular NR families would vary. Colored boxes indicate a NR subfamily is represented by one or more genes for that species. The "inferred bilaterian ancestor" is based largely on a phylogenetic analysis conducted by Bertrand et al. [1]. However, two of these subfamilies are restricted to either protostomes (5B) or deuterostomes (3C) and we have shaded these and used black text to reflect a lack of conclusive support for the presence of these subfamilies in the bilaterian ancestor. Despite the absence of some genes in the D. melanogaster genome, studies of NRs from other protostomes (NR1A from Schistosoma mansoni [50] and NR3A from mollusks and annelids [51,52]) indicate that these subfamilies were present in the bilaterian ancestor and secondarily lost from Drosophila. Similarly, members of NR1B and 1C have been reported in mollusks and annelids [10], and thus are not restricted to deuterostomes. * The sponge Amphimedon queenslandica has two NRs, one that is supported as an ortholog to HNF4 (NR2A) and a second that groups between subfamily NR2A and the rest of the NR superfamily [see also [10]].
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References
-
- Larroux C, Fahey B, Liubicich D, Hinman V, Gauthier M, Gongora M, Green K, Wörheide G, Leys S, Degnan B. Developmental expression of transcription factor genes in a demosponge: insights into the origin of metazoan multicellularity. Evolution and Development. 2006;8:150–173. doi: 10.1111/j.1525-142X.2006.00086.x. - DOI - PubMed
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