PCH-2 and meiotic HORMADs: A module for evolutionary innovation in meiosis?

Abstract

Sexual reproduction and the specialized cell division it relies upon, meiosis, are biological processes that present an incredible degree of both evolutionary conservation and divergence. One clear example of this paradox is the role of the evolutionarily ancient PCH-2/HORMAD module during meiosis. On one hand, the complex, and sometimes disparate, meiotic defects observed when PCH-2 and/or the meiotic HORMADS are mutated in different model systems have prevented a straightforward characterization of their conserved functions. On the other hand, these functional variations demonstrate the impressive molecular rewiring that accompanies evolution of the meiotic processes these factors are involved in. While the defects observed in pch-2 mutants appear to vary in different systems, in this review, I argue that PCH-2 has a conserved meiotic function: to coordinate meiotic recombination with synapsis to ensure an appropriate number and distribution of crossovers. Further, given the dramatic variation in how the events of recombination and synapsis are themselves regulated in different model systems, the mechanistic differences in PCH-2 and meiotic HORMAD function make biological sense when viewed as species-specific elaborations layered onto this fundamental, conserved role.

Keywords: Homologous chromosomes; PCH2; Pachytene checkpoint; Pch2; Recombination; Synapsis; TRIP13.

Fig. 1

Model for PCH-2/Pch2/PCH2/TRIP13 in remodeling meiotic HORMADs. Schematic of different conformers of meiotic HORMADs that have been demonstrated to exist in vitro (extended and closed) and their remodeling by PCH-2 and its orthologs. Whether meiotic HORMADs also adopt the open conformation is unknown.

Fig. 2

Model for Pch2/TRIP13/PCH2 function in systems in which recombination precedes synapsis, such as budding yeast, plants and mice. 1. Pch2 (green hexamer) remodels meiotic HORMADs from their closed conformation, bound to its own closure motif, to the extended conformation to enable its entry into meiotic nuclei and assembly on meiotic chromosomes. 2. During leptotene/zygotene, Pch2 forms puncta on meiotic chromosomes, colocalizing with crossover precursors, remodeling meiotic HORMADs from closed to extended to contribute to the gradual implementation of crossover number and distribution and possibly proofread homolog pairing and synapsis. Yellow ovals represent axis proteins that contain closure motifs and recruit meiotic HORMADs. 3. During pachytene, Pch2 localizes to the synaptonemal complex between synapsed homologous chromosomes, depleting meiotic HORMADs to limit meiotic recombination, drive meiotic progression and participate in the last stages of implementing crossover number and distribution through the remodeling of a reduced pool of meiotic HORMADs on meiotic chromosomes.

Fig. 3

Model for PCH-2 function in systems in which synapsis precedes recombination and PCH-2 localizes to the synaptonemal complex, such as C. elegans. (A) 1. During leptotene/zygotene, Pch2 forms puncta on meiotic chromosomes, remodeling meiotic HORMADs from closed to extended to control to proofread homolog pairing and synapsis. Yellow ovals represent axis proteins that contain closure motifs and recruit meiotic HORMADs. In this system, the assembly of meiotic HORMADs on chromosomes drives meiotic progression. 2. During pachytene, PCH-2 localizes to the synaptonemal complex between synapsed homologous chromosomes, meiotic HORMADs remain on chromosomes and remodeling meiotic HORMADs from closed to extended to contribute to the gradual implementation of crossover number and distribution. The presence of soluble extended conformers of at least one meiotic HORMAD, HTP-1, delays meiotic progression. (B) A model for how PCH-2’s remodeling of meiotic HORMADs could destabilize interhomolog intermediates involved in pairing, synapsis and/or recombination on meiotic chromosomes, contributing to their proofreading and regulation.