title: Human BOULE gene rescues meiotic defects in infertile flies.
abstract: 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.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, CA 94143-0546, USA.
authors.forename: Eugene Yujun
authors.initials: EY
authors.lastname: Xu
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Lee
authors.forename: Ansgar
authors.initials: A
authors.lastname: Klebes
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Turek
authors.forename: Tom B
authors.initials: TB
authors.lastname: Kornberg
authors.forename: Renee A
authors.initials: RA
authors.lastname: Reijo Pera
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000075364:Deleted in Azoospermia 1 Protein; D004330:Drosophila / Q000235:genetics; D029721:Drosophila Proteins; D019143:Evolution, Molecular; D005260:Female; D005298:Fertility / Q000235:genetics*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D006801:Humans; D008297:Male; D008540:Meiosis / Q000235:genetics* / Q000502:physiology; D005810:Multigene Family; D010802:Phylogeny; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D013091:Spermatogenesis / Q000235:genetics; D013094:Spermatozoa / Q000502:physiology*
chemical_list: C095668:DAZ1 protein, human; D000075364:Deleted in Azoospermia 1 Protein; D029721:Drosophila Proteins; D016601:RNA-Binding Proteins; C099859:bol protein, Drosophila