Germline Progenitors Escape the Widespread Phenomenon of Homolog Pairing during Drosophila Development

Abstract

Homolog pairing, which plays a critical role in meiosis, poses a potential risk if it occurs in inappropriate tissues or between nonallelic sites, as it can lead to changes in gene expression, chromosome entanglements, and loss-of-heterozygosity due to mitotic recombination. This is particularly true in Drosophila, which supports organismal-wide pairing throughout development. Discovered over a century ago, such extensive pairing has led to the perception that germline pairing in the adult gonad is an extension of the pairing established during embryogenesis and, therefore, differs from the mechanism utilized in most species to initiate pairing specifically in the germline. Here, we show that, contrary to long-standing assumptions, Drosophila meiotic pairing in the gonad is not an extension of pairing established during embryogenesis. Instead, we find that homologous chromosomes are unpaired in primordial germ cells from the moment the germline can be distinguished from the soma in the embryo and remain unpaired even in the germline stem cells of the adult gonad. We further establish that pairing originates immediately after the stem cell stage. This pairing occurs well before the initiation of meiosis and, strikingly, continues through the several mitotic divisions preceding meiosis. These discoveries indicate that the spatial organization of the Drosophila genome differs between the germline and the soma from the earliest moments of development and thus argue that homolog pairing in the germline is an active process as versus a passive continuation of pairing established during embryogenesis.

TORC1 regulators Iml1/GATOR1 and GATOR2 control meiotic entry and oocyte development in Drosophila

“…S1). In contrast, as has been reported by others (23)(24)(25)(26)(27), we never observed a pachytene configuration in wild-type eight-cell cysts (n = 10). Thus, low Tor ΔP activity results in the premature transition of ovarian cysts from the mitotic cycle to the meiotic cycle.…”

Microtubule-driven nuclear rotations promote meiotic chromosome dynamics

“…We and others have shown recently that this is not the case for autosomal chromosomes in germline stem cells and that homologous chromosomes are actively pairing in the mitotic region preceding entry into meiosis 23,24 . These events take place in a specialized structure called the germarium at the anterior tip of each ovary (Fig.…”

Recombination, Pairing, and Synapsis of Homologs during Meiosis

“…The paradigmatic example is Drosophila somatic pairing (e.g., Joyce et al 2013). Genome-wide somatic pairing also occurs in budding yeast (Weiner and Kleckner 1994;Keeney and Kleckner 1996;Cha et al 2000;Dekker et al 2002), and in stabilized S. pombe diploids (Scherthan et al 1994), including telomere pairing in both organisms (Klein et al 1992;Molnar and Kleckner 2008).…”

“…Genome-wide somatic pairing also occurs in budding yeast (Weiner and Kleckner 1994;Keeney and Kleckner 1996;Cha et al 2000;Dekker et al 2002), and in stabilized S. pombe diploids (Scherthan et al 1994), including telomere pairing in both organisms (Klein et al 1992;Molnar and Kleckner 2008). Pairing in somatic cells also occurs locally, for example, in cases of monoallelic expression in mammalian cells (e.g., X-chromosome inactivation, V(D)J recombination and imprinting; references in Joyce et al 2013;Barakat et al 2014). …”

“…However, recent studies show that germline stem cells do not have somatic pairing, genome wide or specifically in centromere regions. Pairing reestablished five mitotic divisions before the onset of meiosis (Cahoon and Hawley 2013;Christophorou et al 2013;Joyce et al 2013). Interestingly, homologous heterochromatic regions remain paired after prophase, permitting regular segregation of homologs that have failed to acquire a CO/chiasma (Dernburg et al 1996).…”