A widely employed germ cell marker is an ancient disordered protein with reproductive functions in diverse eukaryotes.

Michelle A Carmell,Helen Skaletsky,David C Page,Yueh-Chiang Hu,Vladimir N Uversky,Gregoriy A Dokshin,Daniel W Bellott,Michael Nefedov,Craig C Mello,Josien C Van Wolfswinkel,George C Enders,Peter W Reddien,Kyomi J Igarashi

doi:10.7554/elife.19993

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. Gcna gene 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 of Gcna-mutant C. elegans and 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.

Highlights

Sexual reproduction in eukaryotes is accomplished through meiosis, a specialized cell cycle that generates genetically diverse derivatives
The mouse germline is first distinguished from the surrounding soma as a population of primordial germ cells that migrates toward the developing genital ridge
We find that an antigen widely employed to identify germ cells in mice corresponds to a protein that has been expressed for nearly 2 billion years in cells carrying a heritable genome – whether single cells during meiosis, stem cells that give rise to germ cells, or germ cells themselves

Summary

Introduction

Sexual reproduction in eukaryotes is accomplished through meiosis, a specialized cell cycle that generates genetically diverse derivatives. Meiosis is believed to have evolved once, in the common ancestor of extant eukaryotes, about two billion years ago (Ramesh et al, 2005; Villeneuve and Hillers, 2001). Sexual reproduction via meiosis and utilization of specialized genome defense mechanisms are characteristics of many unicellular eukaryotes, in which every cell contributes to the generation. These properties became germline specific when the distinction between germ cells and somatic cells was made in multicellular organisms, with the germline being tasked with guarding the heritable genome. Certain critical genes encoding proteins associated with the sexual cycle, as well as those required for integrity of the heritable

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