CLONING, SEQUENCING AND PHYLOGENETIC ANALYSIS OF A HUMAN 5-HYDROXYTRYPTAMINE(1D) RECEPTOR PSEUDOGENE

A third member of the human 5HT(1D) gene family has been identified using a combination of homology cloning and DNA sequence analysis. This human gene is most related to the 5HT1D alpha subtype (77% shared identity) and is a pseudogene, based on the lack of an open reading frame (ORF) caused by multiple in-frame stop codons and nucleotide (nt) deletions relative to the functional 5HT(1D alpha) gene (encoding the 5-hydroxytryptamine(1D alpha) receptor). The 5HT(1D) pseudogene also contained an insertion that shares 87% identity to the Alu consensus sequence. Phylogenetic analysis of the three human genes in this family reveals that although the two functional genes, 5HT(1D alpha) and 5HT(1D beta), are detected in all mammalian species examined, the 5HT(1D) pseudogene is only detected in a subset of primates (catarrhines) that evolved approximately 35-45 million years (Myr) ago. Alternatively, based on the 23% divergence between the functional 5HT(1D alpha) gene and the 5HT(1D) pseudogene, we estimate that these two genes began to diverge approximately 50 Myr ago.