Analysis of human Per4.
The molecular mechanism of the circadian pacemaker depends on the oscillatory expression of clock gene constituents. The Drosophila period gene is central to the clock mechanism in these animals. Three homologs of this gene identified in mice (mPer1-3) and humans (hPer1-3) display rhythmic expression and are important for normal clock function. Recently, analysis of the draft sequence of the human genome has revealed the presence of a fourth Per gene family member. Surprisingly, the deduced hPer4 cDNA has no open reading frame encoding a full-length PER-like protein. This sequence is characterized by numerous deletions, insertions, frame shifts and base pair changes, and its genomic structure is devoid of introns. The presence of an MER-2 mobile element fossil within the Per4 locus predicted that this gene would also be present in non-human primates. Rhesus monkey Per4 displays similar sequence anomalies and is 92.8% identical to hPer4. Sequence comparisons indicate that Per4 originated from a Per3 predecessor and that it is relatively new to the Period gene family. We conclude that hPer4 and RmPer4 are pseudogenes and descended from the retrotransposition of an ancestral Per3 gene.