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Open Access Highly Accessed Research

Comparison of complete nuclear receptor sets from the human, Caenorhabditis elegans and Drosophila genomes

Jodi M Maglich1, Ann Sluder3, Xiaojun Guan2, Yunling Shi2, David D McKee1, Kevin Carrick2, Kim Kamdar4, Timothy M Willson1 and John T Moore1*

Author Affiliations

1 Nuclear Receptor Discovery Research

2 Cellular Genomics, GlaxoSmithKline, Research Triangle Park, NC 27709, USA

3 Cambria Biosciences, Bedford, MA 01730, USA

4 Syngenta Inc, Research Triangle Park, NC 27709, USA

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Genome Biology 2001, 2:research0029-research0029.7  doi:10.1186/gb-2001-2-8-research0029

Published: 24 July 2001

Abstract

Background

The availability of complete genome sequences enables all the members of a gene family to be identified without limitations imposed by temporal, spatial or quantitative aspects of mRNA expression. Using the nearly completed human genome sequence, we combined in silico and experimental approaches to define the complete human nuclear receptor (NR) set. This information was used to carry out a comparative genomic study of the NR superfamily.

Results

Our analysis of the human genome identified two novel NR sequences. Both these contained stop codons within the coding regions, indicating that both are pseudogenes. One (HNF4 γ-related) contained no introns and expressed no detectable mRNA, whereas the other (FXR-related) produced mRNA at relatively high levels in testis. If translated, the latter is predicted to encode a short, non-functional protein. Our analysis indicates that there are fewer than 50 functional human NRs, dramatically fewer than in Caenorhabditis elegans and about twice as many as in Drosophila. Using the complete human NR set we made comparisons with the NR sets of C. elegans and Drosophila. Searches for the >200 NRs unique to C. elegans revealed no human homologs. The comparative analysis also revealed a Drosophila member of NR subfamily NR3, confirming an ancient metazoan origin for this subfamily.

Conclusions

This work provides the basis for new insights into the evolution and functional relationships of NR superfamily members.