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Mol Biol Evol. 2008 Jan;25(1):131-43. Epub 2007 Dec 7.

Analysis of nuclear receptor pseudogenes in vertebrates: how the silent tell their stories.

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Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA.


Transcription factor pseudogenes have not been systematically studied before. Nuclear receptors (NRs) constitute one of the largest groups of transcription factors in animals (e.g., 48 NRs in human). The availability of whole-genome sequences enables a global inventory of the NR pseudogenes in a number of vertebrate model organisms. Here we identify the NR pseudogenes in 8 vertebrate organisms and make our results available online at The assignments reveal that NR pseudogenes as a group have characteristics related to generation and distribution contrary to expectations derived from previous large-scale pseudogene studies. In particular, 1) despite its large size, the NR gene family has only a very small number of pseudogenes in each of the vertebrate genomes examined; 2) despite the low transcription levels of NR genes, except for one, all other NR pseudogenes identified in this study are retropseudogenes; and 3) no duplicated NR pseudogenes are found, contrary to the fact that the NR gene family was expanded through several waves of gene duplication events. Our analyses further reveal a number of interesting aspects of NR pseudogenes. Specifically, through careful sequence analysis, we identify remnant introns in 2 mouse retropseudogenes, psiRev-erbbeta and psiLRH1. Generated from partially processed pre-mRNAs, they appear to be rare examples of highly unusual "semiprocessed" pseudogenes. Second, by comparing the genomic sequences, we uncover a pseudogene that is unique to the human lineage relative to chimpanzee. Generated by a recent duplication of a segment in the human genome, this pseudogene is a "duplicated-processed" pseudogene, belonging to a new pseudogene species. Finally, FXRbeta was nonfunctionalized in the human lineage and thus appears to be an example of a rare unitary pseudogene. By comparing orthologous sequences, we dated the FXR-FXRbeta duplication and the nonfunctionalization of FXRbeta in primates.

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