The male-specific region of the Y chromosome, the MSY, differentiates the sexes and comprises 95% of the chromosome's length, and is a mosaic of heterochromatic sequences and three classes of euchromatics sequences: X-transposed, X-degenerate and ampliconic.
The work shows that signaling by retinoic acid (RA), an active derivative of vitamin A, is required for Stra8 expression and thereby meiotic initiation in embryonic ovaries and that cytochrome p450 from the 26 family (CYP26) is responsible for delaying Stra8expression in embryonic testes.
The ages of individual X-Y gene pairs and the locations of their X members on the X chromosome were found to be highly correlated and age decreased in stepwise fashion from thedistal long arm to the distal short arm in at least four "evolutionary strata".
The findings indicate that the X chromosome has a predominant role in pre-meiotic stages of mammalian spermatogenesis, and hypothesize that theX chromosome acquired this prominent role in male germ-cell development as it evolved from an ordinary, unspecialized autosome.
It is concluded that during recent evolution, an average of approximately 600 nucleotides per newborn male have undergone Y–Y gene conversion, which has had an important role in the evolution of multi-copy testis gene families in the MSY.
The region contains a single–copy gene, DAZ (Deleted in AZoospermia), which is transcribed in the adult testis and appears to encode an RNA binding protein, and the possibility that DAZ is AZF should now be explored.
It is suggested that the existence of this deletion as a polymorphism reflects a balance between haploid selection, which culls gr/gr-deleted Y chromosomes from the population, and homologous recombination, which continues to generate newgr/gr deletions.
It is reported that in female embryos lacking Stra8 gene function, the early, mitotic development of germ cells is normal, but these cells then fail to undergo premeiotic DNA replication, meiotic chromosome condensation, cohesion, synapsis and recombination, and genetic data suggest that active differentiation of ovarian germ cells commences at a regulatory point upstream of premeiotics DNA replication.
The discovery of breakpoint hotspots suggest that factors in addition to homology underlie these deletions, which are the largest of all human interstitial deletions for which deletion junctions and complete intervening sequence are available.
This work shows that follistatin (Fst), which encodes a TGFβ superfamily binding protein, is a downstream component of Wnt4 signaling and proposes that WNT4 acts through FST to regulate vascular boundaries and maintain germ cell survival in the ovary.