Evolution of a novel subfamily of nuclear receptors with members that each contain two DNA binding domains

Abstract

Background: Nuclear receptors (NRs) are important transcriptional modulators in metazoans which regulate transcription through binding to the promoter region of their target gene by the DNA binding domain (DBD) and activation or repression of mRNA synthesis through coregulators bound to the ligand binding domain (LBD). NRs typically have a single DBD with a LBD.

Conserved and Exapted Functions of Nuclear Receptors in Animal Development

“…There are multiple examples of gene loss in specific animal clades, as well as massive gene proliferation and divergence in specific clades, such as the radiation of HNF4 NRs in C. elegans [6,11]. Many species have evolved atypical nuclear receptors, including some that lack a DBD or LBD, or have two DBD’s [5,12]. An example of this includes the 2DBD-NRs in the flatworm Schistosoma mansoni , which have two DBD’s in tandem with one LBD [12].…”

“…Many species have evolved atypical nuclear receptors, including some that lack a DBD or LBD, or have two DBD’s [5,12]. An example of this includes the 2DBD-NRs in the flatworm Schistosoma mansoni , which have two DBD’s in tandem with one LBD [12]. Some of the first genetically-defined NRs were discovered in the classic Drosophila patterning screens [13].…”

“…The recent completion and annotation of mollusk, annelid, and platyhelminth genomes has provided additional clarity on patterns of conservation and orthology [12, 15,16]. Including lophotrochozoan NR proteins produces a phylogenetic analysis that is largely consistent with standard nomenclature for nuclear receptors (Figure 1).…”

Nuclear receptors in nematode development: Natural experiments made by a phylum

“…Exceptionally, NRs with two DBD domains are found in some species, e.g. in Platyhelminthes Schistosoma mansoni [5], Schmidtea mediterranea, Dugesia japonica, in the mollusk Lottia gigantea, and in the arthropod Daphnia pulex [6]. Another exception is represented by TLX, whose DBD differs from other NRs and forms a longer signature with additional cysteines [7].…”

“…2) that are divided into seven classes including (A) thyroid hormone receptors α and β (TRα, β) (NR1A1-2), (B) retinoic acid receptors α, β and γ (RARα, β, γ) (NR1B1-3), (C) peroxisome proliferators activated receptors α/β, δ and γ (PPARα/β, δ, γ) (NR1C1-3), (D) RevErbA α and β (NR1D1-2), (F) −ROR α, β and γ (NR1F1-3), (H) −LXR α and β, and FXR (NR1H3,2,4), (I) VDR, PXR, and CAR (NR1I1-3). Platyhelminths NR1 subfamily members that contain 2 DBDs are classified as NR1X [5,6].…”