A gene family required for human germ cell development evolved from an ancient meiotic gene conserved in metazoans

The Deleted in AZoospermia (DAZ) genes encode potential RNA-binding protein s that are expressed exclusively in prenatal and postnatal germ cells and a re strong candidates for human fertility factors. Here we report the identi fication of an additional member of the DAZ gene family, which we have call ed BOULE. With the identification of this gene, it is clear that the human DAZ gene family contains at least three members: DAZ, a Y-chromosome gene c luster that arose 30-40 million years ago and whose deletion is linked to i nfertility in men; DAZL, the "father" of DAZ, a gene that maps to human chr omosome 3 and has homologs required for both female and male germ cell deve lopment in other organisms; and BOULE, a gene that we propose is the "grand father" of DAZ and maps to human chromosome 2. Human and mouse BOULE resemb le the invertebrate meiotic regulator Boule, the proposed ortholog of DAZ, in sequence and expression pattern and hence likely perform a similar meiot ic function. In contrast, the previously identified human DAZ and DAZL are expressed much earlier than BOULE in prenatal germ stem cells and spermatog onia; DAZL also is expressed in female germ cells. These data suggest that homologs of the DAZ gene family can be grouped into two subfamilies (BOULE and DAZL) and that members of the DAZ family evolved from an ancestral meio tic regulator, Boule, to assume distinct, yet overlapping, functions in ger m cell development.