A requirement of the Y chromosome long arm (Yq) for normal spermatogenesis was recognized more than two decades ago when six infertile men were found to have Yq deletions. More recent molecular screening has detected Yq microdeletions in 10-15% of males with idiopathic azoospermia. The DAZ (Deleted in AZoospermia) gene family was isolated from one of the deleted regions. There are seven DAZ genes clustered within a 1-Mbp region in interval 6 of Yq. DAZ homologues are present on the Y chromosomes of only great apes and old-world monkeys, yet all mammals contain a single-copy DAZ-like gene, DAZL1, on their autosomes. DAZ and DAZL1 encode proteins with an RNA recognition motif (RRM) and varying numbers of copies of a DAZ repeat. DAZ has 8-24 copies of the repeat, and DAZL1 has a single copy. DAZ and DAZL1 have 85% sequence similarity over most of their lengths, including the RRM domain and the DAZ repeats, but they have different C-terminal sequences due to a frame shift downstream of the DAZ repeat region. It was proposed that the DAZ genes originated from translocation of an ancestral DAZL1 gene to the Y chromosome, followed by amplification and pruning.
A role for DAZ and DAZL1 in spermatogenesis is supported by their exclusive expression in germ cells, their homology to a Drosophila male infertility gene, boule, and the sterility of Dazll knock-out mice. Male flies with the boule mutation have morphologically normal primary spermatocytes, which fail to enter into meiotic division, suggesting that boule is required for the G2/M transition. Dazl1 knock-out mice are sterile in both sexes, and male mice exhibit a spermatogenic defect significantly different from that of boule flies. The seminiferous tubules contain only a few premeiotic spermatogonia that rarely progress into meiosis, suggesting that Dazl1 is required for both the development and the maintenance of the germ cells. The spermatogenic defects of boule flies and Dazll knock-out mice were partially rescued by a Xenopus Xdazl gene and a human DAZ gene, respectively, indicating conservation of the function of DAZ and Dazl1.
The biological function of DAZ and DAZL1 is unknown. Immunostaining of mouse testicular sections detected DAZL1 abundantly in the cytoplasm of pachytene spermatocytes and to a lesser degree in the cytoplasm of type-B spermatogonia and preleptotene and zygotene spermatocytes. The whereabouts of the human DAZ protein is less certain. It has been localized either to late spermatids and sperm tails or to spermatogonia and primary spermatocytes. In order to gain insights into their function, we studied the ability of DAZ and DAZL1 to bind RNA molecules in vitro and determined the subcellular localization of DAZL1 in mouse testis.