Evidence That Masking of Synapsis Imperfections Counterbalances Quality Control to Promote Efficient Meiosis

Autor: Anne M. Villeneuve, Baptiste Roelens, Susanna Mlynarczyk-Evans
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Zdroj: PLoS Genetics
PLoS Genetics, Vol 9, Iss 12, p e1003963 (2013)
ISSN: 1553-7404
1553-7390
Popis: Reduction in ploidy to generate haploid gametes during sexual reproduction is accomplished by the specialized cell division program of meiosis. Pairing between homologous chromosomes and assembly of the synaptonemal complex at their interface (synapsis) represent intermediate steps in the meiotic program that are essential to form crossover recombination-based linkages between homologs, which in turn enable segregation of the homologs to opposite poles at the meiosis I division. Here, we challenge the mechanisms of pairing and synapsis during C. elegans meiosis by disrupting the normal 1∶1 correspondence between homologs through karyotype manipulation. Using a combination of cytological tools, including S-phase labeling to specifically identify X chromosome territories in highly synchronous cohorts of nuclei and 3D rendering to visualize meiotic chromosome structures and organization, our analysis of trisomic (triplo-X) and polyploid meiosis provides insight into the principles governing pairing and synapsis and how the meiotic program is “wired” to maximize successful sexual reproduction. We show that chromosomes sort into homologous groups regardless of chromosome number, then preferentially achieve pairwise synapsis during a period of active chromosome mobilization. Further, comparisons of synapsis configurations in triplo-X germ cells that are proficient or defective for initiating recombination suggest a role for recombination in restricting chromosomal interactions to a pairwise state. Increased numbers of homologs prolong markers of the chromosome mobilization phase and/or boost germline apoptosis, consistent with triggering quality control mechanisms that promote resolution of synapsis problems and/or cull meiocytes containing synapsis defects. However, we also uncover evidence for the existence of mechanisms that “mask” defects, thus allowing resumption of prophase progression and survival of germ cells despite some asynapsis. We propose that coupling of saturable masking mechanisms with stringent quality controls maximizes meiotic success by making progression and survival dependent on achieving a level of synapsis sufficient for crossover formation without requiring perfect synapsis.
Author Summary Diploid organisms must produce haploid gametes prior to sexual reproduction in order to maintain a constant number of chromosomes from one generation to the next. Ploidy reduction is accomplished during meiosis and requires crossover recombination-based linkages between homologous chromosomes. Here, we manipulate karyotype in C. elegans to probe the mechanisms that govern stable, pairwise, homologous associations essential for crossover formation. We find that chromosomes sort into homolog groups regardless of number prior to stabilizing interactions (“synapsing”) in a preferentially pairwise manner. Increased numbers of homologs delay meiotic progression and/or boost cell death, reflecting operation of quality control mechanisms that either buy time to correct synapsis problems or eliminate defective cells. Moreover, we found evidence for mechanisms that can “mask” synapsis imperfections, thus allowing resumption of meiotic progression and survival of germ cells when synapsis is “good enough”, albeit imperfect. This strategy would maximize meiotic success by making progression and survival contingent on achieving a level of synapsis sufficient for crossover formation without imposing an onerous and unnecessary requirement for perfect synapsis. We suggest that the regulatory logic of coupling saturable masking mechanisms with stringent quality controls may be employed widely to maximize efficiency of biological circuits.
Databáze: OpenAIRE
Externí odkaz: