Cloning, sequencing and phylogenetic analysis of a human 5-hydroxytryptamine 1D receptor pseudogene

A third member of the human 5 HT ID gene family has been identified using a combination of homology cloning and DNA sequence analysis. This human gene is most related to the 5 HT 1 Dα 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 5 HT 1 Dα gene (encoding the 5-hydroxytryptamine 1Dα receptor). The 5 HT 1 D 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, 5 HT 1 Dα and 5 HT 1 Dgb , are detected in all mammalian species examined, the 5 HT 1 D 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 5 HT 1 Dα gene and the 5 HT 1 D pseudogene, we estimate that these two genes began to diverge approximately 50 Myr ago.