Mechanisms of Meiosis

Institut Jean-Pierre Bourgin, UMR1318 INRA-AgroParisTech-ERL3559 CNRS
Bâtiment 7
INRA Centre de Versailles-Grignon
Route de St-Cyr (RD10)
78026 Versailles Cedex France

tél : +33 (0)1 30 83 30 00 - fax : +33 (0)1 30 83 33 19

Meiosis is an essential stage in the life cycle of sexually reproducing organisms. Indeed, meiosis is the specialized cell division that halves the number of chromosomes (from two sets in the parent to one set in gametes), while fertilization restores the original chromosome number. Meiosis is also the stage of development when genetic recombination occurs; it is thus the heart of Mendelian heredity.

While meiosis has been described precisely, the underlying mechanisms remain largely unknown.
Major questions remain unanswered:
- Why and how is the recombination rate along the chromosomes controlled?
- How are the formation and the distribution of the recombination events along the chromosomes?
- Why are the pericentromeric regions refractory to meiotic recombination events?
- What is the signal of interference?
- What is the role of the synaptonemal complex?
- Which actors are involved in the choice between the homologous chromosome or the sister chromatid to repair DNA double-strand breaks?
- How are the chromosomes and then the sister chromatids separated during the two meiotic divisions?
- How are the meiotic divisions regulated?

We are also investigating the consequences of polyploidy (whole genome duplications; WGD) on meiotic recombination. It is now clearly established that all flowering plants have experienced at least one and usually several rounds of whole genome duplications (WGD) during the course of their evolution. Nearly 30% of existing flowering plants are polyploids, including most of the world’s important crops, such as wheat, cotton or oilseed rape. Our work focuses on three major themes: How is meiotic recombination regulated in polyploid (crop) species? To what extent have past WGDs modified the core meiotic “tool-kit”? How can such improved knowledge on recombination be exploited for crop improvement?

We are addressing all these questions using Arabidopsis thaliana, oilseed rape (Brassica napus) and its diploid progenitors as well as Camelina sativa as main model species. Arabidopsis emerged as one of the prominent models in the field of meiosis notably because of the possibility to combine large-scale genetic studies and the wide range of molecular and cytological tools. Brassica napus and Camelina sativa are allopolyploid species related to Arabidopsis.

Our projects aim to elucidate comprehensively the mechanisms of meiosis. For this, we combine a whole set of state-of-the-art genetic (most notably genetic screens), genomic, molecular biology, cytogenetic, biochemistry and bio-informatic approaches. Our work contributes to a better understanding of a key biological mechanism. Increasing our knowledge on meiosis, in addition to its intrinsic interest, has also important implications for agriculture and medicine.

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FANCM limits meiotic crossovers.

Gonzalo A, Lucas MO, Charpentier C, Sandmann G, Andrew Lloyd A, Jenczewski E (2019) Reducing MSH4 copy number prevents meiotic crossovers between non-homologous chromosomes in Brassica napus. Nature Communications. (full test) Communiqué de presse INRA

Séguéla-Arnaud M, Choinard S, Larchevêque C, Girard C, Froger N, Crismani W, Mercier R. (2016) RMI1 and TOP3a limit meiotic CO formation through their C-terminal domains. Nucleic Acids Res. Dec 13. pii: gkw1210. [Epub ahead of print] PMID: 27965412 (pdf)

Cifuentes, M., Jolivet, S., Cromer, L., et al. (2016) TDM1 Regulation Determines the Number of Meiotic Divisions. PLOS Genet., 12, e1005856. (pdf)

Vrielynck N, Chambon A, Vezon D, Pereira L, ChelyshevaL, De Muyt A, Mézard C, Mayer C, Grelon M. (2016). A DNA topoisomerase VI-like complex initiates meiotic recombination. Science.351(6276):939-43. doi: 10.1126/science.aad5196 (full text) communiqué de presse INRA

Mézard C, Tagliaro Jahns M, Grelon M (2015). Where to cross? New insights into the location of meiotic crossovers. Trends Genet 1–9 (pubmed)

Mercier R, Mézard C, Jenczewski E, Macaisne N, Grelon M. (2015). The Molecular Biology of Meiosis in Plants. Annu Rev Plant Biol 66: 297–327 (pubmed)

Girard, C., Chelysheva, L., Choinard, S., Froger, N., Macaisne, N., Lehmemdi, A., Mazel, J., Crismani, W. and Mercier, R. (2015) AAA-ATPase FIDGETIN-LIKE 1 and Helicase FANCM Antagonize Meiotic Crossovers by Distinct Mechanisms M. Lichten, ed. PLOS Genet., 11, e1005369. (pdf)

Mercier, R., Mézard, C., Jenczewski, E., Macaisne, N. and Grelon, M. (2015) The molecular biology of meiosis in plants. Annu. Rev. Plant Biol., 66, 297–327.

Portemer, V., Renne, C., Guillebaux, A. and Mercier, R. (2015) Large genetic screens for gynogenesis and androgenesis haploid inducers in Arabidopsis thaliana failed to identify mutants. Front. Plant Sci., 6,1–6. (pdf)

Séguéla-Arnaud, M., Crismani, W., Larchevêque, C., et al. (2015) Multiple mechanisms limit meiotic crossovers: TOP3a and two BLM homologs antagonize crossovers in parallel to FANCM. Proc. Natl. Acad. Sci. U. S. A., 112, 4713–4718.

Duroc, Y., Lemhemdi, A., Larcheveque, C., Hurel, A., Cuacos, M., Cromer, L., Armstrong, S.J., Chelysheva, L. and Mercier, R. (2014) The kinesin AtPSS1 promotes synapsis and is required for proper crossover distribution in meiosis. PLoS Genet., 10, e1004674. (pdf)

Girard, C., Crismani, W., Froger, N., Mazel, J., Lemhemdi, A., Horlow, C. and Mercier, R. (2014) FANCM-associated proteins MHF1 and MHF2, but not the other Fanconi anemia factors, limit meiotic crossovers. Nucleic Acids Res., 42, 9087–9095.

Jahns MT, Vezon D, Chambon A, Pereira L, Falque M, Martin OC, Chelysheva L, Grelon M. (2014). Crossover localisation is regulated by the neddylation posttranslational regulatory pathway. PLoS Biol. Aug 12;12(8):e1001930. doi: 10.1371/journal.pbio.1001930. (online)

Lloyd, A.H., Ranoux, M., Vautrin, S., Glover, N., Fourment, J., Charif, D., Choulet, F., Lassalle, G., Marande, W., Tran, J., Granier, F., Pingault, L., Remay, A., Marquis, C., Belcram, H., Chalhoub, B., Feuillet, C., Berges, H., Sourdille, P. and Jenczewski, E. (2014) Meiotic gene evolution: can you teach a new dog new tricks? Mol Biol Evol, 31, 1724-1727 (PubMed)

Grandont, L., Cunado, N., Coriton, O., Huteau, V., Eber, F., Chevre, A.M., Grelon, M., Chelysheva, L. and Jenczewski, E. (2014) Homoeologous Chromosome Sorting and Progression of Meiotic Recombination in Brassica napus: Ploidy Does Matter! The Plant cell, 26, 1448-1463 (Abstract)

Jenczewski E, Mercier R, Macaisne N, and Mézard C. (2013). Meiosis: Recombination and the control of cell division. In: Plant Genome Diversity Volume 2: 121-136. Springer-Verlag. I.J. Leitch et al. (Eds)

Grandont, L., Jenczewski, E. and Lloyd, A. (2013) Meiosis and its deviations in polyploid plants. Cytogenetic and genome research, 140, 171-184.

Uanschou C, Ronceret A, Von Harder M, De Muyt A, Vezon D, Pereira L, Chelysheva L, Kobayashi W, Kurumizaka H, Schlögelhofer P, Grelon M. (2013). Sufficient amounts of functional HOP2/MND1 complex promote interhomolog DNA repair but are dispensable for intersister DNA repair during meiosis in Arabidopsis. Plant Cell 25(12):4924-40. doi: 10.1105/tpc.113.118521. (pubmed)

Mézard C, Macaisne N, Grelon M (2013). La Méiose in La Reproduction Animale et Humaine. Editions Quae _ Éditions Cemagref, Cirad, Ifremer$

Jenczewski, E. (2013) Evolution: he who grabs too much loses all. Curr Biol, 23, R961-963 (pdf)

Chelysheva L, Grandont L, Grelon M (2013). Immunolocalization of meiotic proteins in Brassicacae: method 1 in  Plant Meiosis (eds : Pawlowski W Grelon M and Armstrong S). Series: Methods in Molecular Biology (Series Editor: John M. Walker) 990:93-101. (pubmed)

Pawlowski, W.P.; Grelon, M; Armstrong, S (Eds.) (2013). Plant Meiosis, Methods and Protocols, Series: Methods in Molecular Biology, Vol. 990 XV, 238 p. 52 illus., 28 illus. in color. Humana Press

Drouaud, J, Khademian, J., Giraut, L., and Mézard, C. (2013). Contrasted patterns of crossover and non crossover events at Arabidopsis thaliana meiotic recombination hotspots. PLos Gentics DOI: 10.1371/journal.pgen.1003922 (online)

Cifuentes, M., Rivard, M., Pereira, L., Chelysheva, L. and Mercier, R. (2013) Haploid meiosis in Arabidopsis: double-strand breaks are formed and repaired but without synapsis and crossovers. PLoS One,8, e72431. (pdf)

Jenczewski, E., Mercier, R., Macaisne, N., and Mezard, C. (2013) Meiosis: Recombination and the Control of Cell Division, in Plant Genome Diversity Volume 2 (Greilhuber, J., Dolezel, J., and Wendel, J. F., Eds.), pp 121–136. Springer Vienna, Vienna

Crismani, W., and Mercier, R. (2013) Plant Meiosis, Plant Meiosis (Pawlowski, W. P., Grelon, M., and Armstrong, S., Eds.), pp 227–234. Humana Press, Totowa, NJ.

Crismani, W., Portemer, V., Froger, N., Chelysheva, L., Horlow, C., Vrielynck, N. and Mercier, R. (2013) MCM8 Is Required for a Pathway of Meiotic Double-Strand Break Repair Independent of DMC1 in Arabidopsis thaliana. PLoS Genet., 9, e1003165. (pdf)

Crismani, W., Girard, C., and Mercier, R. (2013) Tinkering with meiosis., Journal of experimental botany 64, 55–6

Crismani W, Mercier R (2012) What limits meiotic crossovers? Cell cycle (Georgetown, Tex) 11: 3527–3528.

Eloy NB, Gonzalez N, Van Leene J, Maleux K, Vanhaeren H, et al. (2012) SAMBA, a plant-specific anaphase-promoting complex/cyclosome regulator is involved in early development and A-type cyclin stabilization. Proceedings of the National Academy of Sciences of the United States of America 109: 13853–13858.

Crismani W, Girard C, Froger N, Pradillo M, Santos JL, et al. (2012) FANCM limits meiotic crossovers. Science (New York, NY) 336: 1588–1590.

Cromer L, Heyman J, Touati S, Harashima H, Araou E, et al. (2012) OSD1 Promotes Meiotic Progression via APC/C Inhibition and Forms a Regulatory Network with TDM and CYCA1;2/TAM. PLoS genetics 8: e1002865. (pdf)

Yelina NE, Choi K, Chelysheva L, Macaulay M, De Snoo B, Wijnker E, Miller N, Drouaud J, Grelon M, Copenhaver GP, et al (2012). Epigenetic remodeling of meiotic crossover frequency in Arabidopsis thaliana DNA methyltransferase mutants. PLoS genetics 8: e1002844 (online)

Chelysheva L, Vezon D, Chambon A, Gendrot G, Pereira L, Lemhemdi A, Vrielynck N, Le Guin S, Novatchkova M, Grelon M (2012). The Arabidopsis HEI10 is a new ZMM protein related to Zip3. PLoS genetics 8: e1002799 (online)

Nicolas, S.D., Monod, H., Eber, F., Chevre, A.M. and Jenczewski, E. (2012) Non-random distribution of extensive chromosome rearrangements in Brassica napus depends on genome organization. Plant J, 70, 691-703 ( pdf)

Giraut, L., Falque, M., Drouaud, J., Pereira, L., Martin, O.C., and Mézard, C. (2011). Genome-wide crossover distribution in Arabidopsis thaliana meiosis reveals sex specific patterns long chromosomes. PLos Gentics DOI: 10.1371/journal.pgen.1002354 (online)

Jenczewski, E., Mercier, R., Macaisne, N., and Mézard, C. (2011). Meiosis : recombination and the control of cell division. Plant génome diversity, ed. J. Greilhuber, J. Wendel, I.J. Leitch and J. Dolezel. Springer-Verlag Wien New York, submitted

Drouaud, J. and Mézard, C. Characterization of meiotic crossovers in pollen from Arabidopsis thaliana (2011). Methods Mol. Biol. 745:223-49. doi: 10.1007/978-1-61779-129-1_14. (pubmed)

Macaisne N, Vignard J, Mercier R*. SHOC1 and PTD form an XPF-ERCC1-like complex that is required for formation of class I crossovers. J Cell Sci. 2011 15;124(Pt of cohesins, histones and MLH1.Cytogenetics and Genome Research. 129:143-153

d'Erfurth, I., Cromer, L, Jolivet, S, Girard, C, Horlow, C, Sun, Y, To, JP, Berchowitz, LE, Copenhaver, GP, and Mercier, R*. The cyclin-A CYCA1;2/TAM is required for the meiosis I to meiosis II transition and cooperates with OSD1 for the prophase to first meiotic division transition. PLoS Genet. 2010. e1000989. (pdf)

M. Cifuentes, F. Eber, M.O. Lucas, M. Lode, AM Chèvre and E. Jenczewski (2010) Repeated polyploidy drove different levels of crossover suppression between homeologous chromosomes in Brassica napus allohaploids. The Plant Cell 22: 2265-2276 (pdf)

M. Leflon, Grandont, F. Eber, V. Huteau, O. Coriton, L. Chelysheva, Jenczewski E and AM Chèvre (2010) Crossovers get a boost in Brassica allotriploid and allotetraploid hybrids The Plant Cell 22: 2253-2264 (Full text)

M. Cifuentes, L. Grandont, G. Moore, AM Chèvre and Eric Jenczewski (2010) Genetic regulation of meiosis in polyploid species: new insights into an old question. The New Phytologist 186(1):29-36

E. Szadkowski, F. Eber, V. Huteau, O. Coriton, M. Manzanares-Dauleux, R. Delourme, C. Huneau, B. Chalhoub, E. Jenczewski and AM. Chèvre (2010) The first meiosis in newly synthesized Brassica napus: a genome blender? The New Phytologist 186(1):102-112

S. Nicolas, M. Leflon, H. Monod, F. Eber, O. Coriton, V. Huteau, A.-M. Chèvre et E. Jenczewski (2009) Genetic regulation of meiotic crossovers between related genomes in Brassica napus haploids and hybrids. The Plant Cell 21: 373-385

d'Erfurth I, Jolivet S, Froger N, Catrice O, Novatchkova M, Mercier R*. Turning Meiosis into Mitosis. PLoS Biol 2009. 7(6): e1000124. (pdf)

Pouilly N., R. Delourme, K. Alix and E. Jenczewski (2008) Repetitive sequence-derived markers tag centromeres and telomeres and provide insights into chromosome evolution in Brassica napus. Chromosome Research 16: 686-700.

S. Nicolas, G. LeMignon, F. Eber, O. Coriton, H. Monod, V. Clouet, V. Huteau, A. Lostanlen, R. Delourme, B. Chalhoub, C. D. Ryder, A.-M. Chèvre et E. Jenczewski (2007) Homeologous recombination is responsible for most of the rearrangements that occur during meiosis of Brassica napus haploids. Genetics. 175: 487-503

Z. Liu, K. Adamczyk, M. Manzanares-Dauleux, F. Eber, M.-O. Lucas, R. Delourme, A.-M. Chèvre et E. Jenczewski (2006) Mapping PrBn and Other Quantitative Trait Loci Responsible for the Control of Homoeologous Chromosome Pairing in Oilseed Rape (Brassica napus L.) Haploids. Genetics. 174(3):1583-96

W. Albertin, P. Brabant, O. Catrive, F. Eber, E. Jenczewski, A.M. Chèvre et H. Thiellement (2005) Autopolyploidy in cabbage (Brassica oleracea L.) does not alter significantly the proteomes of green tissues. Proteomics 5: 2131-2139

E. Jenczewski et K. Alix. (2004) From diploids to allopolyploids: the emergence of pairing control genes. Critical Reviews in Plant Sciences 23(1): 21-45

E. Jenczewski, F. Eber, A. Grimaud, S. Huet, M.O. Lucas, H. Monod et A.M. Chèvre (2003) PrBn: a major gene controlling homoeologous pairing in oilseed rape (Brassica napus) dihaploids. Genetics 164: 645-654.

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