Journal article
Variation in genome-wide levels of meiotic recombination is established at the onset of prophase in mammalian males
PLoS genetics, Vol.10(1), pp.e1004125-e1004125
01/2014
Handle:
https://hdl.handle.net/2376/100661
PMCID: PMC3907295
PMID: 24497841
Abstract
Segregation of chromosomes during the first meiotic division relies on crossovers established during prophase. Although crossovers are strictly regulated so that at least one occurs per chromosome, individual variation in crossover levels is not uncommon. In an analysis of different inbred strains of male mice, we identified among-strain variation in the number of foci for the crossover-associated protein MLH1. We report studies of strains with "low" (CAST/EiJ), "medium" (C3H/HeJ), and "high" (C57BL/6J) genome-wide MLH1 values to define factors responsible for this variation. We utilized immunofluorescence to analyze the number and distribution of proteins that function at different stages in the recombination pathway: RAD51 and DMC1, strand invasion proteins acting shortly after double-strand break (DSB) formation, MSH4, part of the complex stabilizing double Holliday junctions, and the Bloom helicase BLM, thought to have anti-crossover activity. For each protein, we identified strain-specific differences that mirrored the results for MLH1; i.e., CAST/EiJ mice had the lowest values, C3H/HeJ mice intermediate values, and C57BL/6J mice the highest values. This indicates that differences in the numbers of DSBs (as identified by RAD51 and DMC1) are translated into differences in the number of crossovers, suggesting that variation in crossover levels is established by the time of DSB formation. However, DSBs per se are unlikely to be the primary determinant, since allelic variation for the DSB-inducing locus Spo11 resulted in differences in the numbers of DSBs but not the number of MLH1 foci. Instead, chromatin conformation appears to be a more important contributor, since analysis of synaptonemal complex length and DNA loop size also identified consistent strain-specific differences; i.e., crossover frequency increased with synaptonemal complex length and was inversely related to chromatin loop size. This indicates a relationship between recombination and chromatin compaction that may develop as DSBs form or earlier during establishment of the meiotic axis.
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Details
- Title
- Variation in genome-wide levels of meiotic recombination is established at the onset of prophase in mammalian males
- Creators
- Brian Baier - School of Molecular Biosciences, Washington State University, Pullman, Washington, United States of AmericaPatricia Hunt - School of Molecular Biosciences, Washington State University, Pullman, Washington, United States of AmericaKarl W Broman - Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, Wisconsin, United States of AmericaTerry Hassold - School of Molecular Biosciences, Washington State University, Pullman, Washington, United States of America
- Publication Details
- PLoS genetics, Vol.10(1), pp.e1004125-e1004125
- Academic Unit
- Molecular Biosciences, School of
- Publisher
- United States
- Grant note
- R01 ES013527 / NIEHS NIH HHS R01 HD21341 / NICHD NIH HHS R01 HD021341 / NICHD NIH HHS R37 HD021341 / NICHD NIH HHS
- Identifiers
- 99900546688801842
- Language
- English
- Resource Type
- Journal article