Xu Eugene Yujun, Lee Douglas F, Klebes Ansgar, Turek Paul J, Kornberg Tom B, Reijo Pera Renee A
Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, CA 94143-0546, USA.
Hum Mol Genet. 2003 Jan 15;12(2):169-75. doi: 10.1093/hmg/ddg017.
Defects in human germ cell development are common and yet little is known of genes required for germ cell development in men and women. The pathways that develop germ cells appear to be conserved broadly, at least in outline, in organisms as diverse as flies and humans beginning with allocation of cells to the germ cell lineage, migration of these cells to the fetal gonad, mitotic proliferation and meiosis of the germ cells, and maturation into sperm and eggs. In model organisms, a few thousand genes may be required for germ cell development including meiosis. To date, however, no genes that regulate critical steps of reproduction have been shown to be functionally conserved from flies to humans. This may be due in part to strong selective pressures that are thought to drive reproductive genes to high degrees of divergence. Here, we investigated the micro- and macro-evolution of the BOULE gene, a member of the human DAZ (deleted in azoospermia) gene family, within primates, within mammals and within metazoans. We report that sequence divergence of BOULE is unexpectedly low and that rapid evolution is not detectable. We extend the evolutionary analysis of BOULE to the level of phyla and show that a human BOULE transgene can advance meiosis in infertile boule mutant flies. This is the first demonstration that a human reproductive gene can rescue reproductive defects in a fly. These studies lend strong support to the idea that BOULE may encode a key conserved switch that regulates progression of germ cells through meiosis in men.
人类生殖细胞发育缺陷很常见，但我们对男性和女性生殖细胞发育所需的基因却知之甚少。生殖细胞发育的途径似乎在很大程度上是保守的，至少大致如此，从将细胞分配到生殖细胞谱系开始，这些细胞迁移到胎儿性腺，生殖细胞进行有丝分裂增殖和减数分裂，最终成熟为精子和卵子，在从果蝇到人类等多种生物中都是如此。在模式生物中，包括减数分裂在内的生殖细胞发育可能需要数千个基因。然而，迄今为止，尚未发现任何调节生殖关键步骤的基因在从果蝇到人类的过程中具有功能保守性。这可能部分归因于强大的选择压力，这些压力被认为会促使生殖基因高度分化。在此，我们研究了人类DAZ（无精子症缺失基因）基因家族成员BOULE基因在灵长类动物、哺乳动物和后生动物中的微观和宏观进化。我们报告称，BOULE的序列分歧出乎意料地低，且未检测到快速进化。我们将BOULE的进化分析扩展到门的水平，并表明人类BOULE转基因可以促进不育的boule突变果蝇的减数分裂。这是首次证明人类生殖基因可以挽救果蝇的生殖缺陷。这些研究有力地支持了这样一种观点，即BOULE可能编码一个关键的保守开关，调节男性生殖细胞通过减数分裂的进程。
