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

¹Nuclear Receptor Discovery Research

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

³Cambria Biosciences, Bedford, MA 01730, USA

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

author email corresponding author email

Genome Biology 2001, 2:research0029.1-0029.7doi:10.1186/gb-2001-2-8-research0029


Published:	24 July 2001

Subject areas: Genome studies, Evolution, Biochemistry and structural biology, Cell biology

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.