title: Evolutionary history of the vertebrate period genes.
abstract: Circadian clock genes are remarkably conserved between eucoelomates. Although Drosophila has one copy of each major component, vertebrates have two or (in the case of the Period genes) three paralogs (Per1-3). We investigated the possibility that the vertebrate Per genes arose through two genome duplications during the emergence of vertebrates. Phylogenetic trees have placed zebrafish and mammalian Per1 and 2 together in a separate branch from Per3. The positions of four coding region splice sites were conserved between Drosophila per and the human paralogs, the fifth one being unique to Drosophila. The human PER genes shared the positions of all coding region splice sites, except the first two in PER1 and PER2 (which PER3 lacks). The phases of all splice sites were conserved between all four genes with two exceptions. Analysis of all genes within 10 Mb of the human PER1-3 genes, which are located 7.8-8.8 Mb from the telomeres on chromosomes 17, 2, and 1, identified several orthologous neighbors shared by at least two PER genes. Two gene families, HES (hairy and Enhancer of Split) and KIF1 (kinesin-like protein 1), were represented in all three of these paralogons. Although no functional fourth human PER paralog exists, five representatives from the same gene families were found close to the telomer of chromosome 3. We conclude that the ancestral chordate Per gene underwent two duplication events, giving rise to Per1-3 and a lost fourth paralog.
authors.affiliation: Centre for Chronobiology, School of Biomedical and Molecular Sciences, University of Surrey, Guildford, GU2 7XH, UK. m.von.schantz@surrey.ac.uk
authors.forename: Malcolm
authors.initials: M
authors.lastname: von Schantz
authors.forename: Aaron
authors.initials: A
authors.lastname: Jenkins
authors.forename: Simon N
authors.initials: SN
authors.lastname: Archer
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001683:Biological Clocks / Q000235:genetics*; D017124:Conserved Sequence; D004330:Drosophila / Q000235:genetics; D019143:Evolution, Molecular; D005091:Exons; D005136:Eye Proteins / Q000235:genetics*; D020440:Gene Duplication; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics*; D056950:Period Circadian Proteins; D010802:Phylogeny; D014157:Transcription Factors / Q000235:genetics*; D015027:Zebrafish; D029961:Zebrafish Proteins
chemical_list: D005136:Eye Proteins; D009687:Nuclear Proteins; C539022:PER1 protein, human; C421902:PER2 protein, human; C512644:PER3 protein, human; D056950:Period Circadian Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; C539026:per1a protein, zebrafish; C512647:per3 protein, zebrafish