title: A widely employed germ cell marker is an ancient disordered protein with reproductive functions in diverse eukaryotes.
abstract: The advent of sexual reproduction and the evolution of a dedicated germline in multicellular organisms are critical landmarks in eukaryotic evolution. We report an ancient family of GCNA (germ cell nuclear antigen) proteins that arose in the earliest eukaryotes, and feature a rapidly evolving intrinsically disordered region (IDR). Phylogenetic analysis reveals that GCNA proteins emerged before the major eukaryotic lineages diverged; GCNA predates the origin of a dedicated germline by a billion years.Gcnagene expression is enriched in reproductive cells across eukarya - either just prior to or during meiosis in single-celled eukaryotes, and in stem cells and germ cells of diverse multicellular animals. Studies ofGcna-mutantC. elegansand mice indicate that GCNA has functioned in reproduction for at least 600 million years. Homology to IDR-containing proteins implicated in DNA damage repair suggests that GCNA proteins may protect the genomic integrity of cells carrying a heritable genome.
authors.affiliation: Whitehead Institute, Cambridge, United States.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Carmell
authors.affiliation: RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, United States.
authors.forename: Gregoriy A
authors.initials: GA
authors.lastname: Dokshin
authors.affiliation: Whitehead Institute, Cambridge, United States.|Howard Hughes Medical Institute, Chevy Chase, United States.
authors.forename: Helen
authors.initials: H
authors.lastname: Skaletsky
authors.affiliation: Whitehead Institute, Cambridge, United States.
authors.forename: Yueh-Chiang
authors.initials: YC
authors.lastname: Hu
authors.affiliation: Whitehead Institute, Cambridge, United States.
authors.forename: Josien C
authors.initials: JC
authors.lastname: van Wolfswinkel
authors.affiliation: Whitehead Institute, Cambridge, United States.
authors.forename: Kyomi J
authors.initials: KJ
authors.lastname: Igarashi
authors.affiliation: Whitehead Institute, Cambridge, United States.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Bellott
authors.affiliation: BACPAC Resources, Children's Hospital Oakland, Oakland, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Nefedov
authors.affiliation: Whitehead Institute, Cambridge, United States.|Howard Hughes Medical Institute, Chevy Chase, United States.|Department of Biology, Massachusetts Institute of Technology, Cambridge, United States.
authors.forename: Peter W
authors.identifier: 0000-0002-5569-333X
authors.initials: PW
authors.lastname: Reddien
authors.affiliation: Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, United States.
authors.forename: George C
authors.initials: GC
authors.lastname: Enders
authors.affiliation: Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, United States.
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Uversky
authors.affiliation: RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, United States.|Howard Hughes Medical Institute, Chevy Chase, United States.
authors.forename: Craig C
authors.initials: CC
authors.lastname: Mello
authors.affiliation: Whitehead Institute, Cambridge, United States.|Howard Hughes Medical Institute, Chevy Chase, United States.|Department of Biology, Massachusetts Institute of Technology, Cambridge, United States.
authors.forename: David C
authors.identifier: 0000-0001-9920-3411
authors.initials: DC
authors.lastname: Page
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000235:genetics* / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development; D056890:Eukaryota / Q000235:genetics; D019143:Evolution, Molecular; D005786:Gene Expression Regulation / Q000235:genetics; D016678:Genome / Q000235:genetics; D023281:Genomics; D005854:Germ Cells / Q000254:growth & development / Q000378:metabolism*; D008540:Meiosis / Q000235:genetics; D010802:Phylogeny; D012098:Reproduction / Q000235:genetics*
chemical_list: D034961:Antigens, Nuclear
keywords: C. elegans; GCNA; Spartan; TRA98; Wss1; developmental biology; evolutionary biology; genomics; germline; intrinsically disordered proteins; mouse; stem cells