-
Science Advances Oct 2023In almost all sexually reproducing organisms, meiotic recombination and cell division require the synapsis of homologous chromosomes by a large proteinaceous structure,...
In almost all sexually reproducing organisms, meiotic recombination and cell division require the synapsis of homologous chromosomes by a large proteinaceous structure, the synaptonemal complex (SC). While the SC's overall structure is highly conserved across eukaryotes, its constituent proteins diverge between phyla. Transverse filament protein, SYCP1, spans the width of the SC and undergoes amino-terminal head-to-head self-assembly in vitro through a motif that is unusually highly conserved across kingdoms of life. Here, we report creation of mouse mutants, and , that target SYCP1's head-to-head interface. L106E resulted in a complete loss of synapsis, while L102E had no apparent effect on synapsis, in agreement with their differential effects on the SYCP1 head-to-head interface in molecular dynamics simulations. In mice, homologs aligned and recruited low levels of mutant SYCP1 and other SC proteins, but the absence of synapsis led to failure of crossover formation and meiotic arrest. We conclude that SYCP1's conserved head-to-head interface is essential for meiotic chromosome synapsis in vivo.
Topics: Animals; Mice; Chromosome Pairing; Homologous Recombination; Meiosis; Nuclear Proteins; Synaptonemal Complex
PubMed: 37862414
DOI: 10.1126/sciadv.adi1562 -
GigaScience Dec 2022The swamp buffalo (Bubalus bubalis carabanesis) is an economically important livestock supplying milk, meat, leather, and draft power. Several female buffalo genomes...
BACKGROUND
The swamp buffalo (Bubalus bubalis carabanesis) is an economically important livestock supplying milk, meat, leather, and draft power. Several female buffalo genomes have been available, but the lack of high-quality male genomes hinders studies on chromosome evolution, especially Y, as well as meiotic recombination.
RESULTS
Here, a chromosome-level genome with a contig N50 of 72.2 Mb and a fine-scale recombination map of male buffalo were reported. We found that transposable elements (TEs) and structural variants (SVs) may contribute to buffalo evolution by influencing adjacent gene expression. We further found that the pseudoautosomal region (PAR) of the Y chromosome is subject to stronger purification selection. The meiotic recombination map showed that there were 2 obvious recombination hotspots on chromosome 8, and the genes around them were mainly related to tooth development, which may have helped to enhance the adaption of buffalo to inferior feed. Among several genomic features, TE density has the strongest correlation with recombination rates. Moreover, the TE subfamily, SINE/tRNA, is likely to play a role in driving recombination into SVs.
CONCLUSIONS
The male genome and sperm sequencing will facilitate the understanding of the buffalo genomic evolution and functional research.
Topics: Male; Female; Animals; Semen; Bison; Genomics; Buffaloes; Chromosomes
PubMed: 37589307
DOI: 10.1093/gigascience/giad063 -
The American Naturalist Feb 2020Sex differences in overall recombination rates are well known, but little theoretical or empirical attention has been given to how and why sexes differ in their...
Sex differences in overall recombination rates are well known, but little theoretical or empirical attention has been given to how and why sexes differ in their recombination landscapes: the patterns of recombination along chromosomes. In the first scientific review of this phenomenon, we find that recombination is biased toward telomeres in males and more uniformly distributed in females in most vertebrates and many other eukaryotes. Notable exceptions to this pattern exist, however. Fine-scale recombination patterns also frequently differ between males and females. The molecular mechanisms responsible for sex differences remain unclear, but chromatin landscapes play a role. Why these sex differences evolve also is unclear. Hypotheses suggest that they may result from sexually antagonistic selection acting on coding genes and their regulatory elements, meiotic drive in females, selection during the haploid phase of the life cycle, selection against aneuploidy, or mechanistic constraints. No single hypothesis, however, can adequately explain the evolution of sex differences in all cases. Sex-specific recombination landscapes have important consequences for population differentiation and sex chromosome evolution.
Topics: Animals; Biological Evolution; Chromosomes; Crossing Over, Genetic; Epigenesis, Genetic; Female; Humans; Male; Meiosis; Plants; Recombination, Genetic; Sex Characteristics
PubMed: 32017625
DOI: 10.1086/704943 -
The Plant Cell Apr 2020The Arabidopsis () cyclin-dependent kinase G1 (CDKG1) is necessary for recombination and synapsis during male meiosis at high ambient temperature. In the mutant,...
The Arabidopsis () cyclin-dependent kinase G1 (CDKG1) is necessary for recombination and synapsis during male meiosis at high ambient temperature. In the mutant, synapsis is impaired and there is a dramatic reduction in the number of class I crossovers, resulting in univalents at metaphase I and pollen sterility. Here, we demonstrate that CDKG1 is necessary for the processing of recombination intermediates in the canonical ZMM recombination pathway and that loss of CDKG1 results in increased class II crossovers. While synapsis and events associated with class I crossovers are severely compromised in a mutant, they can be restored by increasing the number of recombination intermediates in the double mutant. Despite this, recombination intermediates are not correctly resolved, leading to the formation of chromosome aggregates at metaphase I. Our results show that CDKG1 acts early in the recombination process and is necessary to stabilize recombination intermediates. Finally, we show that the effect on recombination is not restricted to meiosis and that CDKG1 is also required for normal levels of DNA damage-induced homologous recombination in somatic tissues.
Topics: Arabidopsis; Arabidopsis Proteins; Chromosome Pairing; Chromosomes, Plant; Crossing Over, Genetic; Cyclin-Dependent Kinases; Homologous Recombination; Meiosis; Models, Biological; Mutation; Phenotype
PubMed: 32047050
DOI: 10.1105/tpc.19.00942 -
International Journal of Biological... 2022About 10% of reproductive-aged couples suffer from infertility. However, the genetic causes of human infertility cases are largely unknown. Meiosis produces haploid... (Review)
Review
About 10% of reproductive-aged couples suffer from infertility. However, the genetic causes of human infertility cases are largely unknown. Meiosis produces haploid gametes for fertilization and errors in meiosis are associated with human infertility in both males and females. Successful meiosis relies on the assembly of the synaptonemal complex (SC) between paired homologous chromosomes during the meiotic prophase. The SC is ultrastructurally and functionally conserved, promoting inter-homologous recombination and crossover formation, thus critical for accurate meiotic chromosome segregation. With whole-genome/exome sequencing and mouse models, a list of mutations in SC coding genes has been linked to human infertility. Here we summarize those findings. We also analyzed SC gene variants present in the general population and presented complex interaction networks associated with SC components. Whether a combination of genetic variations and environmental factors causes human infertility demands further investigations.
Topics: Adult; Animals; Chromosome Segregation; Female; Germ Cells; Humans; Infertility; Male; Meiosis; Mice; Synaptonemal Complex
PubMed: 35342360
DOI: 10.7150/ijbs.67843 -
PloS One 2023Meiotic recombination is a crucial cellular process, being one of the major drivers of evolution and adaptation of species. In plant breeding, crossing is used to...
Meiotic recombination is a crucial cellular process, being one of the major drivers of evolution and adaptation of species. In plant breeding, crossing is used to introduce genetic variation among individuals and populations. While different approaches to predict recombination rates for different species have been developed, they fail to estimate the outcome of crossings between two specific accessions. This paper builds on the hypothesis that chromosomal recombination correlates positively to a measure of sequence identity. It presents a model that uses sequence identity, combined with other features derived from a genome alignment (including the number of variants, inversions, absent bases, and CentO sequences) to predict local chromosomal recombination in rice. Model performance is validated in an inter-subspecific indica x japonica cross, using 212 recombinant inbred lines. Across chromosomes, an average correlation of about 0.8 between experimental and prediction rates is achieved. The proposed model, a characterization of the variation of the recombination rates along the chromosomes, can enable breeding programs to increase the chances of creating novel allele combinations and, more generally, to introduce new varieties with a collection of desirable traits. It can be part of a modern panel of tools that breeders can use to reduce costs and execution times of crossing experiments.
Topics: Humans; Plant Breeding; Genome; Chromosomes; Homologous Recombination; Phenotype; Oryza
PubMed: 36795698
DOI: 10.1371/journal.pone.0281804 -
G3 (Bethesda, Md.) Feb 2021Homoeologous recombination, aneuploidy, and other genetic changes are common in resynthesized allopolyploid Brassica napus. In contrast, the chromosomes of cultivars...
Homoeologous recombination, aneuploidy, and other genetic changes are common in resynthesized allopolyploid Brassica napus. In contrast, the chromosomes of cultivars have long been considered to be meiotically stable. To gain a better understanding of the underlying mechanisms leading to stabilization in the allopolyploid, the behavior of chromosomes during meiosis can be compared by unambiguous chromosome identification between resynthesized and natural B. napus. Compared with natural B. napus, resynthesized lines show high rates of nonhomologous centromere association, homoeologous recombination leading to translocation, homoeologous chromosome replacement, and association and breakage of 45S rDNA loci. In both natural and resynthesized B. napus, we observed low rates of univalents, A-C bivalents, and early sister chromatid separations. Reciprocal homoeologous chromosome exchanges and double reductions were photographed for the first time in meiotic telophase I. Meiotic errors were non-uniformly distributed across the genome in resynthesized B. napus, and in particular homoeologs sharing synteny along their entire length exhibited multivalents at diakinesis and polysomic inheritance at telophase I. Natural B. napus appeared to resolve meiotic errors mainly by suppressing homoeologous pairing, resolving nonhomologous centromere associations and 45S rDNA associations before diakinesis, and reducing homoeologous cross-overs.
Topics: Aneuploidy; Brassica napus; Chromosomes, Plant; Genome, Plant; Meiosis; Polyploidy
PubMed: 33704431
DOI: 10.1093/g3journal/jkaa011 -
International Journal of Molecular... Jun 2020Meiosis is a specialized cell division that gives raise to four haploid gametes from a single diploid cell. During meiosis, homologous recombination is crucial to ensure... (Review)
Review
Meiosis is a specialized cell division that gives raise to four haploid gametes from a single diploid cell. During meiosis, homologous recombination is crucial to ensure genetic diversity and guarantee accurate chromosome segregation. Both the formation of programmed meiotic DNA double-strand breaks (DSBs) and their repair using homologous chromosomes are essential and highly regulated pathways. Similar to other processes that take place in the context of chromatin, histone posttranslational modifications (PTMs) constitute one of the major mechanisms to regulate meiotic recombination. In this review, we focus on specific PTMs occurring in histone tails as driving forces of different molecular events, including meiotic recombination and transcription. In particular, we concentrate on the influence of H3K4me3, H2BK123ub, and their corresponding molecular machineries that write, read, and erase these histone marks. The Spp1 subunit within the Complex of Proteins Associated with Set1 (COMPASS) is a critical regulator of H3K4me3-dependent meiotic DSB formation. On the other hand, the PAF1c (RNA polymerase II associated factor 1 complex) drives the ubiquitination of H2BK123 by Rad6-Bre1. We also discuss emerging evidence obtained by cryo-electron microscopy (EM) structure determination that has provided new insights into how the "cross-talk" between these two marks is accomplished.
Topics: Animals; Chromatin; Chromosomes; DNA Breaks, Double-Stranded; DNA-Binding Proteins; Endodeoxyribonucleases; Histone-Lysine N-Methyltransferase; Histones; Homologous Recombination; Humans; Meiosis; Methylation; Protein Processing, Post-Translational; Ubiquitin-Conjugating Enzymes; Ubiquitination
PubMed: 32630409
DOI: 10.3390/ijms21124510 -
Nucleic Acids Research Apr 2023At meiosis, programmed meiotic DNA double-strand breaks are repaired via homologous recombination, resulting in crossovers (COs). From a large excess of DNA...
At meiosis, programmed meiotic DNA double-strand breaks are repaired via homologous recombination, resulting in crossovers (COs). From a large excess of DNA double-strand breaks that are formed, only a small proportion gets converted into COs because of active mechanisms that restrict CO formation. The Fanconi anemia (FA) complex proteins AtFANCM, MHF1 and MHF2 were previously identified in a genetic screen as anti-CO factors that function during meiosis in Arabidopsis thaliana. Here, pursuing the same screen, we identify FANCC as a new anti-CO gene. FANCC was previously only identified in mammals because of low primary sequence conservation. We show that FANCC, and its physical interaction with FANCE-FANCF, is conserved from vertebrates to plants. Further, we show that FANCC, together with its subcomplex partners FANCE and FANCF, regulates meiotic recombination. Mutations of any of these three genes partially rescues CO-defective mutants, which is particularly marked in female meiosis. Functional loss of FANCC, FANCE, or FANCF results in synthetic meiotic catastrophe with the pro-CO factor MUS81. This work reveals that FANCC is conserved outside mammals and has an anti-CO role during meiosis together with FANCE and FANCF.
Topics: Humans; Arabidopsis; DNA; Fanconi Anemia Complementation Group C Protein; Fanconi Anemia Complementation Group F Protein; Fanconi Anemia Complementation Group Proteins; Homologous Recombination; Meiosis
PubMed: 36652992
DOI: 10.1093/nar/gkac1244 -
Nature Oct 2020During prophase of the first meiotic division, cells deliberately break their DNA. These DNA breaks are repaired by homologous recombination, which facilitates proper...
During prophase of the first meiotic division, cells deliberately break their DNA. These DNA breaks are repaired by homologous recombination, which facilitates proper chromosome segregation and enables the reciprocal exchange of DNA segments between homologous chromosomes. A pathway that depends on the MLH1-MLH3 (MutLγ) nuclease has been implicated in the biased processing of meiotic recombination intermediates into crossovers by an unknown mechanism. Here we have biochemically reconstituted key elements of this pro-crossover pathway. We show that human MSH4-MSH5 (MutSγ), which supports crossing over, binds branched recombination intermediates and associates with MutLγ, stabilizing the ensemble at joint molecule structures and adjacent double-stranded DNA. MutSγ directly stimulates DNA cleavage by the MutLγ endonuclease. MutLγ activity is further stimulated by EXO1, but only when MutSγ is present. Replication factor C (RFC) and the proliferating cell nuclear antigen (PCNA) are additional components of the nuclease ensemble, thereby triggering crossing-over. Saccharomyces cerevisiae strains in which MutLγ cannot interact with PCNA present defects in forming crossovers. Finally, the MutLγ-MutSγ-EXO1-RFC-PCNA nuclease ensemble preferentially cleaves DNA with Holliday junctions, but shows no canonical resolvase activity. Instead, it probably processes meiotic recombination intermediates by nicking double-stranded DNA adjacent to the junction points. As DNA nicking by MutLγ depends on its co-factors, the asymmetric distribution of MutSγ and RFC-PCNA on meiotic recombination intermediates may drive biased DNA cleavage. This mode of MutLγ nuclease activation might explain crossover-specific processing of Holliday junctions or their precursors in meiotic chromosomes.
Topics: Amino Acid Motifs; Amino Acid Sequence; Cell Cycle Proteins; Chromosomes, Human; Conserved Sequence; Crossing Over, Genetic; DNA; DNA Cleavage; DNA Repair Enzymes; DNA, Cruciform; Endonucleases; Exodeoxyribonucleases; Humans; Meiosis; MutL Protein Homolog 1; MutL Proteins; MutS Proteins; Proliferating Cell Nuclear Antigen; Replication Protein C
PubMed: 32814904
DOI: 10.1038/s41586-020-2592-2