Linkage of the Nuclear Hormone Receptor Genes NR1D2, THRB, and RARB: Evidence for an Ancient, Large-Scale Duplication

The THRA gene encoding thyroid hormone receptor α shares an unusual partial overlap with the NR1D1 gene encoding the orphan receptor Rev-ErbAα. Though THRA and NR1D1 have close relatives in THRB and NR1D2, which encode TRβ and Rev-ErbAβ, these β isoforms do not share an analogous overlap. Here we report that the human THRB and NR1D2 genes are separated by approximately 1 Mb on chromosome 3 and that these two genes are also linked to the RARB gene, which encodes retinoic acid receptor β. Since previous results indicate that the THRA/NR1D1 locus is also linked to the RARA gene, these results suggest that the two receptor gene clusters were generated by a single large-scale duplication.