Publication Date:
2012-06-13
Description:
Background: The nuclear receptors (NRs) are an important class of transcription factors that are conservedacross animal phyla. Canonical NRs consist of a DNA-binding domain (DBD) and ligandbindingdomain (LBD). While most animals have 20-40 NRs, nematodes of the genusCaenorhabditis have experienced a spectacular proliferation and divergence of NR genes.The LBDs of evolutionarily-conserved Caenorhabditis NRs have diverged sharply from theirDrosophila and vertebrate orthologs, while the DBDs have been strongly conserved. TheNR2E family of NRs play critical roles in development, especially in the nervous system. Inthis study, we explore the phylogenetics and function of the NR2E family of Caenorhabditiselegans, using an in vivo assay to test LBD function. Results: Phylogenetic analysis reveals that the NR2E family of NRs consists of three broadlyconservedclades of orthologous NRs. In C. elegans, these clades are defined by nhr-67, fax-1and nhr-239. The vertebrate orthologs of nhr-67 and fax-1 are Tlx and PNR, respectively.While the nhr-239 clade includes orthologs in insects (Hr83), an echinoderm, and ahemichordate, the gene appears to have been lost from vertebrate lineages. The C. elegansand C. briggsae nhr-239 genes have an apparently-truncated and highly-diverged LBDregion. An additional C. elegans NR2E gene, nhr-111, appears to be a recently-evolvedparalog of fax-1; it is present in C. elegans, but not C. briggsae or other animals withcompletely-sequenced genomes. Analysis of the relatively unstudied nhr-111 and nhr-239genes demonstrates that they are both expressed--nhr-111 very broadly and nhr-239 in asmall subset of neurons. Analysis of the FAX-1 LBD in an in vivo assay revealed that it is notrequired for at least some developmental functions. Conclusions: Our analysis supports three conserved clades of NR2E receptors, only two of which arerepresented in vertebrates, indicating three ancestral NR2E genes in the urbilateria. The lackof a requirement for a FAX-1 LBD suggests that the relatively high level of sequencedivergence for Caenorhabditis LBDs reflects relaxed selection on the primary sequence asopposed to divergent positive selection. This observation is consistent with a model in whichdivergence of some Caenorhabditis LBDs is allowed, at least in part, by the absence of aligand requirement.
Electronic ISSN:
1471-2148
Topics:
Biology
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