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

Abstract

The Deleted in AZoospermia (DAZ) genes encode potential RNAbinding proteins that are expressed exclusively in prenatal and postnatal germ cells and are strong candidates for human fertility factors. Here we report the identification of an additional member of the DAZ gene family, which we have called 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 cluster that arose 30 -40 million years ago and whose deletion is linked to infertility in men; DAZL, the ''father'' of DAZ, a gene that maps to human chromosome 3 and has homologs required for both female and male germ cell development in other organisms; and BOULE, a gene that we propose is the ''grandfather'' of DAZ and maps to human chromosome 2. Human and mouse BOULE resemble the invertebrate meiotic regulator Boule, the proposed ortholog of DAZ, in sequence and expression pattern and hence likely perform a similar meiotic function. In contrast, the previously identified human DAZ and DAZL are expressed much earlier than BOULE in prenatal germ stem cells and spermatogonia; 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 meiotic regulator, Boule, to assume distinct, yet overlapping, functions in germ cell development.

Differential expression of fertility genes boule and dazl in Chinese sturgeon (Acipenser sinensis), a basal fish

“…related to DAZ than to boule (Xu et al 2001). Consequently, the autosomal dazl gene is considered the ancestor of the DAZ gene through transposition and repeated amplification and pruning (Gromoll et al 1999;Shan et al 1996).…”

“…However, the third family member, boule, has been identified in species ranging from sea anemones through humans (Shah et al 2010). It is reasonable, therefore, to propose that the dazl gene arose from a duplication of boule during vertebrate evolution (Shah et al 2010;Xu et al 2001).…”

“…The DAZ (deleted in Azoospermia) gene family has been suggested to play essential roles in the generation of male and female gametes in both vertebrates and invertebrates (Shah et al 2010;Xu et al 2001). This gene family consists in a Y-linked DAZ gene cluster and the autosomal dazl and boule genes, all of which encode germ cellspecific RNA-binding proteins with a common RNArecognition motif and at least one copy of DAZ repeat (Xu et al 2001).…”

“…The DAZ (deleted in Azoospermia) gene family has been suggested to play essential roles in the generation of male and female gametes in both vertebrates and invertebrates (Shah et al 2010;Xu et al 2001). This gene family consists in a Y-linked DAZ gene cluster and the autosomal dazl and boule genes, all of which encode germ cellspecific RNA-binding proteins with a common RNArecognition motif and at least one copy of DAZ repeat (Xu et al 2001). The Y-linked DAZ gene cluster is restricted to catarrhine primates (Agulnik et al 1998;Gromoll et al 1999), while dazl homologs are found only in vertebrates, such as zebrafish (Maegawa et al 1999), medaka (Xu et al 2007), rainbow trout (Li et al 2011), gibel carp (Peng et al 2009), Xenopus (Houston et al 1998), axolotl (Johnson et al 2001), chicken (Rengaraj et al 2010), mouse (Cooke et al 1996) and human (Seboun et al 1997), where they are more closely Huan Ye and Chuang-Ju Li contributed equally to this work.…”

Deleted in Azoospermia-Like Enhances In Vitro Derived Porcine Germ Cell Formation and Meiosis

“…DAZL is known to be expressed during gametogenesis in both PGCs and oocytes at all stages of maturation in humans, mice, pigs, and Xenopus laevis [8][9][10][11]. The expression of DAZ family genes is specific to germ cells [12]. In addition, the role of the DAZ family on germline development appears to be conserved across species from invertebrates to mammals, which is evident by the finding that human Dazl can partially rescue the Drosophila boule mutant [13].…”