Iyer Harini, Issigonis Melanie, Sharma Prashant P, Extavour Cassandra G, Newmark Phillip A
Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801; Howard Hughes Medical Institute, University of Illinois at Urbana-Champaign, Urbana, IL 61801;
Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138.
Proc Natl Acad Sci U S A. 2016 Jun 21;113(25):E3509-18. doi: 10.1073/pnas.1521341113. Epub 2016 Jun 2.
Mutations in Deleted in Azoospermia (DAZ), a Y chromosome gene, are an important cause of human male infertility. DAZ is found exclusively in primates, limiting functional studies of this gene to its homologs: boule, required for meiotic progression of germ cells in invertebrate model systems, and Daz-like (Dazl), required for early germ cell maintenance in vertebrates. Dazl is believed to have acquired its premeiotic role in a vertebrate ancestor following the duplication and functional divergence of the single-copy gene boule. However, multiple homologs of boule have been identified in some invertebrates, raising the possibility that some of these genes may play other roles, including a premeiotic function. Here we identify two boule paralogs in the freshwater planarian Schmidtea mediterranea Smed-boule1 is necessary for meiotic progression of male germ cells, similar to the known function of boule in invertebrates. By contrast, Smed-boule2 is required for the maintenance of early male germ cells, similar to vertebrate Dazl To examine if Boule2 may be functionally similar to vertebrate Dazl, we identify and functionally characterize planarian homologs of human DAZL/DAZ-interacting partners and DAZ family mRNA targets. Finally, our phylogenetic analyses indicate that premeiotic functions of planarian boule2 and vertebrate Dazl evolved independently. Our study uncovers a premeiotic role for an invertebrate boule homolog and offers a tractable invertebrate model system for studying the premeiotic functions of the DAZ protein family.
无精子症缺失基因（DAZ）是一种Y染色体基因，其突变是人类男性不育的重要原因。DAZ仅在灵长类动物中发现，这限制了对该基因的功能研究，只能研究其同源物：无脊椎动物模型系统中生殖细胞减数分裂进程所必需的boule，以及脊椎动物中早期生殖细胞维持所必需的类DAZ（Dazl）。据信，在单拷贝基因boule复制和功能分化后，Dazl在脊椎动物祖先中获得了减数分裂前的作用。然而，在一些无脊椎动物中已经鉴定出多个boule同源物，这增加了这些基因中的一些可能发挥其他作用的可能性，包括减数分裂前的功能。在这里，我们在淡水涡虫地中海涡虫中鉴定出两个boule旁系同源物。Smed-boule1对雄性生殖细胞的减数分裂进程是必需的，类似于boule在无脊椎动物中的已知功能。相比之下，Smed-boule2是早期雄性生殖细胞维持所必需的，类似于脊椎动物的Dazl。为了研究Boule2是否在功能上与脊椎动物的Dazl相似，我们鉴定并功能性地表征了人类DAZL/DAZ相互作用伙伴和DAZ家族mRNA靶标的涡虫同源物。最后，我们的系统发育分析表明，涡虫boule2和脊椎动物Dazl的减数分裂前功能是独立进化的。我们的研究揭示了无脊椎动物boule同源物的减数分裂前作用，并为研究DAZ蛋白家族的减数分裂前功能提供了一个易于处理的无脊椎动物模型系统。
