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Letter

Genomic Analysis of the Nuclear Receptor Family: New Insights Into Structure, Regulation, and Evolution From the Rat Genome

¹ Human Genome Sequencing Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA ² Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA ³ Huffington Center on Aging, Department of Otolaryngology, Baylor College of Medicine, Houston, Texas 77030, USA ⁴ Department of Microbiology and Molecular Genetics, University of Texas Medical School, Houston, Texas 77225, USA

Completion of the Rattus norvegicus genome sequence enabled a global inventory and analysis of the nuclear receptors (NRs) in three mammalian species. Forty-nine NR members were found in mouse, 48 in human. Forty-seven were found in the rat, with gaps at the locations expected for the other two. Pairwise comparisons of their distribution in rat, mouse, and human identified 11 syntenic NR gene blocks, including three small clusters of two or three closely related genes, each spanning 40 kb to 1700 kb. The exon structure of the ligand-binding domain suggests that exon shuffling has played a role in the evolution of this family. An invariant splice junction in all members of the NR family except LXR suggests a functional role for the intron. The ligand-binding domains of PXR and CAR are among the most divergent in the family. Their higher nucleotide substitution rates may be related to the central role played by these two NRs in the metabolism of the foreign compounds and may have resulted from limited positive selection.

⁵ Corresponding author.
E-MAIL wheeler{at}bcm.tmc.edu; FAX (713)798-6977.

[Supplemental material is available online at www.genome.org.]

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