Reproduction Abstracts

Introduction: For two decades, an antibody recognizing germ cell nuclear antigen (GCNA) has been widely used to identify mouse germ cells. The antigen, highly germ cell specific and expressed coincident with a key developmental transition as migrating germ cells enter the gonad, has heretofore not been identified. Here, we reveal GCNA as the founding member of a novel, ancient family of germ cell enriched proteins found across eukaryotes, including all major animal classes, plants, and fungi.

Materials and methods: Immunoprecipitation, mass spectrometry, and computational analysis.

Results and discussion: We have determined that GCNA is the product of an X-linked gene encoding an acidic and highly repetitive protein. Largely due to the unique amino acid composition and rapid evolution of proteins in this family, orthologs in most species, including mouse, have been overlooked due to poor annotation. All GCNA orthologs contain a 300–800 amino acids domain that is likely intrinsically disordered. Furthermore, GCNA orthologs outside of the rodent lineage share a well-conserved uncharacterized domain. In species for which expression data is available, gene products of GCNA orthologs are enriched in reproductive organs or specifically in germ cells, and in some species, they are required for fertility. GCNA-related genes are more ancient than the classical germ cell genes Dazl/Boule and Vasa, which are confined to metazoa. The tremendous evolutionary depth of this family suggests its involvement in a fundamental aspect of germ cell biology.