Four mouse POU domain genomic DNA clones--Brain-1, Brain-2, Brain-4, and Scip--and Brain-2 cDNA, which are expressed in adult brain, were cloned and the coding and noncoding regions of the genes were sequenced. The amino acid sequences of the four POU domains are highly conserved; sequences in other regions of the proteins also are conserved but to a lesser extent. The absence of introns from the coding regions of the four POU domain genes and the similarity of amino acid sequences of the corresponding proteins suggest that the coding region of the ancestral class III POU domain gene lacked introns and therefore may have originated by reverse transcription of a molecule of POU domain mRNA followed by insertion of the cDNA into germ cell genomic DNA. Additional duplications of the ancestral class III POU domain gene (or mRNA) would create the Brain-1, Brain-2, Brain-4, and Scip genes.