Evolutionary amplification of a pseudogene.

The family of mouse major urinary protein (MUP) genes has about 35 members, clustered together on chromosome 4. Most of the genes belong to two major subfamilies (group 1 and group 2) each with 12-15 members. Recently we showed that most of the group 1 and group 2 genes are arranged in pairs, each containing a group 1 and a group 2 gene in divergent transcriptional orientation, with 15 kilobases of DNA between the two cap sites. Here we present the nucleotide sequence of the first exon of six group 1 genes and four group 2 genes. The data confirm the close relationship of the genes within each group and the considerable divergence of the two groups from each other. The four group 2 genes all carry the same nonsense mutation in codon 7 of the sequence that specifies the mature protein. Thus, not only do these genes have a common ancestor, but also it seems that their amplification followed the mutation of the ancestor to a pseudogene. Taking into account the 3' flanking regions of the two genes, the overall size of each gene-pair is about 45 kilobases. The sequencing data supports our earlier suggestion that this 45 kilobase domain is the unit of Mup amplification.