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?

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.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 s