title: An X-to-autosome retrogene is required for spermatogenesis in mice.
abstract: We identified the gene carrying the juvenile spermatogonial depletion mutation (jsd), a recessive spermatogenic defect mapped to mouse chromosome 1 (refs. 1,2). We localized jsd to a 272-kb region and resequenced this area to identify the underlying mutation: a frameshift that severely truncates the predicted protein product of a 2.3-kb genomic open reading frame. This gene, Utp14b, evidently arose through reverse transcription of an mRNA from an X-linked gene and integration of the resulting cDNA into an intron of an autosomal gene, whose promoter and 5' untranslated exons are shared with Utp14b. To our knowledge, Utp14b is the first protein-coding retrogene to be linked to a recessive mammalian phenotype. The X-linked progenitor of Utp14b is the mammalian ortholog of yeast Utp14, which encodes a protein required for processing of pre-rRNA and hence for ribosome assembly. Our findings substantiate the hypothesis that mammalian spermatogenesis is supported by autosomal retrogenes that evolved from X-linked housekeeping genes to compensate for silencing of the X chromosome during male meiosis. We find that Utp14b-like retrogenes arose independently and were conserved during evolution in at least four mammalian lineages. This recurrence implies a strong selective pressure, perhaps to enable ribosome assembly in male meiotic cells.
authors.affiliation: Howard Hughes Medical Institute, Whitehead Institute, and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Bradley
authors.forename: Andrew
authors.initials: A
authors.lastname: Baltus
authors.forename: Helen
authors.initials: H
authors.lastname: Skaletsky
authors.forename: Morgan
authors.initials: M
authors.lastname: Royce-Tolland
authors.forename: Ken
authors.initials: K
authors.lastname: Dewar
authors.forename: David C
authors.initials: DC
authors.lastname: Page
mesh_terms: D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D017124:Conserved Sequence; D016368:Frameshift Mutation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D010802:Phylogeny; D016415:Sequence Alignment; D013091:Spermatogenesis / Q000235:genetics*; D014960:X Chromosome