SHORT INTRONS INTERRUPTING THE OCT-2 POU DOMAIN MAY PREVENT RECOMBINATION BETWEEN POU FAMILY GENES WITHOUT INTERFERING WITH POTENTIAL POU DOMAIN SHUFFLING IN EVOLUTION

Transcription factors are often encoded by gene families that share th e same type of DNA binding domain. The POU domain genes are one such p aradigm. We compared the genomic DNA encoding the POU domain of the Oc t-2 genes in human and mouse. In both species this domain is split int o a cluster of four exons by short, highly diverged introns. We postul ate that the main role of these introns is to prevent ectopic homologo us recombination with other members of the POU gene family with its po tentially deleterious effects in somatic and germline cells. Such rapi dly diverging introns may generally promote evolution by facilitating the maintenance of duplicated genes. The use of different codons for t he same protein domain among members of a gene family may be a slower process that serves a similar purpose. Introns that split conserved do mains such as the POU domain do not conform to the exon shuffling hypo thesis originally put forward by W. Gilbert (1978). However, we note t hat the introns flanking the POU domain are in the same phase, i.e. in terrupt codons in the same reading frame. Thus we propose that the ent ire POU domain, which is encoded by a tight cluster of exons, has been shuffled together during evolution as a functional unit, or 'shufflon '.