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The FEBS Journal Feb 2010Sexual reproduction depends on the success of faithful chromosome transmission during meiosis to yield viable gametes. Central to meiosis is the process of recombination... (Review)
Review
Sexual reproduction depends on the success of faithful chromosome transmission during meiosis to yield viable gametes. Central to meiosis is the process of recombination between paternal and maternal chromosomes, which boosts the genetic diversity of progeny and ensures normal homologous chromosome segregation. Imperfections in meiotic recombination are the source of de novo germline mutations, abnormal gametes, and infertility. Thus, not surprisingly, cells have developed a variety of mechanisms and tight controls to ensure sufficient and well-distributed recombination events within their genomes, the details of which remain to be fully elucidated. Local and genome-wide studies of normal and genetically engineered cells have uncovered a remarkable stochasticity in the number and positioning of recombination events per chromosome and per cell, which reveals an impressive level of flexibility. In this minireview, we summarize our contemporary understanding of meiotic recombination and its control mechanisms, and address the seemingly paradoxical and poorly understood diversity of recombination sites. Flexibility in the distribution of meiotic recombination events within genomes may reside in regulation at the chromatin level, with histone modifications playing a recently recognized role.
Topics: Animals; Caenorhabditis elegans; Chromosome Pairing; Chromosome Segregation; Crossing Over, Genetic; DNA Breaks, Double-Stranded; DNA Topoisomerases, Type II; Endodeoxyribonucleases; Histones; Humans; Infertility; Meiosis; Mice; Recombination, Genetic; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Schizosaccharomyces; Sister Chromatid Exchange
PubMed: 20015080
DOI: 10.1111/j.1742-4658.2009.07502.x -
Molecular Biology and Evolution Mar 2021Genetic recombination characterized by reciprocal exchange of genes on paired homologous chromosomes is the most prominent event in meiosis of almost all sexually...
Genetic recombination characterized by reciprocal exchange of genes on paired homologous chromosomes is the most prominent event in meiosis of almost all sexually reproductive organisms. It contributes to genome stability by ensuring the balanced segregation of paired homologs in meiosis, and it is also the major driving factor in generating genetic variation for natural and artificial selection. Meiotic recombination is subjected to the control of a highly stringent and complex regulating process and meiotic recombination frequency (MRF) may be affected by biological and abiotic factors such as sex, gene density, nucleotide content, and chemical/temperature treatments, having motivated tremendous researches for artificially manipulating MRF. Whether genome polyploidization would lead to a significant change in MRF has attracted both historical and recent research interests; however, tackling this fundamental question is methodologically challenging due to the lack of appropriate methods for tetrasomic genetic analysis, thus has led to controversial conclusions in the literature. This article presents a comprehensive and rigorous survey of genome duplication-mediated change in MRF using Saccharomyces cerevisiae as a eukaryotic model. It demonstrates that genome duplication can lead to consistently significant increase in MRF and rate of crossovers across all 16 chromosomes of S. cerevisiae, including both cold and hot spots of MRF. This ploidy-driven change in MRF is associated with weakened recombination interference, enhanced double-strand break density, and loosened chromatin histone occupation. The study illuminates a significant evolutionary feature of genome duplication and opens an opportunity to accelerate response to artificial and natural selection through polyploidization.
Topics: Crossing Over, Genetic; DNA Breaks, Double-Stranded; Gene Duplication; Meiosis; Models, Genetic; Ploidies; Saccharomyces cerevisiae
PubMed: 32898273
DOI: 10.1093/molbev/msaa219 -
PloS One Aug 2009A fundamental goal of single nucleotide polymorphism (SNP) genotyping is to determine the sharing of alleles between individuals across genomic loci. Such analyses have...
BACKGROUND
A fundamental goal of single nucleotide polymorphism (SNP) genotyping is to determine the sharing of alleles between individuals across genomic loci. Such analyses have diverse applications in defining the relatedness of individuals (including unexpected relationships in nominally unrelated individuals, or consanguinity within pedigrees), analyzing meiotic crossovers, and identifying a broad range of chromosomal anomalies such as hemizygous deletions and uniparental disomy, and analyzing population structure.
PRINCIPAL FINDINGS
We present SNPduo, a command-line and web accessible tool for analyzing and visualizing the relatedness of any two individuals using identity by state. Using identity by state does not require prior knowledge of allele frequencies or pedigree information, and is more computationally tractable and is less affected by population stratification than calculating identity by descent probabilities. The web implementation visualizes shared genomic regions, and generates UCSC viewable tracks. The command-line version requires pedigree information for compatibility with existing software and determining specified relationships even though pedigrees are not required for IBS calculation, generates no visual output, is written in portable C++, and is well-suited to analyzing large datasets. We demonstrate how the SNPduo web tool identifies meiotic crossover positions in siblings, and confirm our findings by visualizing meiotic recombination in synthetic three-generation pedigrees. We applied SNPduo to 210 nominally unrelated Phase I / II HapMap samples and, consistent with previous findings, identified six undeclared pairs of related individuals. We further analyzed identity by state in 2,883 individuals from multiplex families with autism and identified a series of anomalies including related parents, an individual with mosaic loss of chromosome 18, an individual with maternal heterodisomy of chromosome 16, and unexplained replicate samples.
CONCLUSIONS
SNPduo provides the ability to explore and visualize SNP data to characterize the relatedness between individuals. It is compatible with, but distinct from, other established analysis software such as PLINK, and performs favorably in benchmarking studies for the analyses of genetic relatedness.
Topics: Genomics; Humans; Meiosis; Polymorphism, Single Nucleotide; Recombination, Genetic
PubMed: 19696932
DOI: 10.1371/journal.pone.0006711 -
Genome Dynamics 2009In the last 30 years it has become evident that patterns of meiotic recombination can be highly variable among individuals. The evidence comes from both low and high... (Review)
Review
In the last 30 years it has become evident that patterns of meiotic recombination can be highly variable among individuals. The evidence comes from both low and high resolution analyses of hotspots of recombination in human and other species. In addition, a comparison of the recombination profiles in closely related species such as human and chimpanzee reveals essentially no correlation in the position of hotspots. Although the variation in hotspots of meiotic recombination is clearly documented, the mechanisms responsible for such variation are far from being understood. Here we will review the available evidence of natural variation in meiotic recombination and will discuss potential implications of this variation on the functional mechanisms of crossover formation and control.
Topics: Computational Biology; Genetic Variation; Humans; Meiosis; Recombination, Genetic
PubMed: 18948711
DOI: 10.1159/000166623 -
Methods in Molecular Biology (Clifton,... 2009Traditional methods for surveying meiotic recombination in humans are limited to pedigree and linkage disequilibrium analyses. We have developed assays that allow the... (Review)
Review
Traditional methods for surveying meiotic recombination in humans are limited to pedigree and linkage disequilibrium analyses. We have developed assays that allow the direct detection of crossover and gene conversion molecules in batches of sperm DNA. To date, we have characterized 26 recombination hotspots by allele-specific PCR and selectively amplified recombinant DNA molecules from these regions. These analyses have revealed that meiotic crossover hotspots in humans are highly localized and flanked by DNA segments where recombination is suppressed. The centers of crossover hotspots are also active in noncrossover recombination, displaying short conversion tracts.
Topics: Algorithms; Cytogenetic Analysis; Humans; Male; Meiosis; Models, Biological; Polymerase Chain Reaction; Recombination, Genetic; Spermatozoa
PubMed: 19799191
DOI: 10.1007/978-1-59745-527-5_20 -
The Plant Journal : For Cell and... Jul 2018During meiotic prophase I chromosomes undergo dramatic conformational changes that accompany chromosome condensation, pairing and recombination between homologs. These...
During meiotic prophase I chromosomes undergo dramatic conformational changes that accompany chromosome condensation, pairing and recombination between homologs. These changes include the anchoring of telomeres to the nuclear envelope and their clustering to form a bouquet. In plants, these events have been studied and illustrated in intact meiocytes of species with large genomes. Arabidopsis thaliana is an excellent genetic model in which major molecular pathways that control synapsis and recombination between homologs have been uncovered. Yet the study of chromosome dynamics is hampered by current cytological methods that disrupt the three-dimensional (3D) architecture of the nucleus. Here we set up a protocol to preserve the 3D configuration of A. thaliana meiocytes. We showed that this technique is compatible with the use of a variety of antibodies that label structural and recombination proteins and were able to highlight the presence of clustered synapsis initiation centers at the nuclear periphery. By using fluorescence in situ hybridization we also studied the behavior of chromosomes during pre-meiotic G and prophase I, revealing the existence of a telomere bouquet during A. thaliana male meiosis. In addition we showed that the number of telomeres in a bouquet and its volume vary greatly, thus revealing the complexity of telomere behavior during meiotic prophase I. Finally, by using probes that label subtelomeric regions of individual chromosomes, we revealed differential localization behaviors of chromosome ends. Our protocol opens new areas of research for investigating chromosome dynamics in A. thaliana meiocytes.
Topics: Arabidopsis; Chromosomes, Plant; Imaging, Three-Dimensional; Meiosis; Prophase; Recombination, Genetic; Telomere
PubMed: 29681056
DOI: 10.1111/tpj.13942 -
Science (New York, N.Y.) Dec 2012Meiotic recombination creates genetic diversity and ensures segregation of homologous chromosomes. Previous population analyses yielded results averaged among...
Meiotic recombination creates genetic diversity and ensures segregation of homologous chromosomes. Previous population analyses yielded results averaged among individuals and affected by evolutionary pressures. We sequenced 99 sperm from an Asian male by using the newly developed amplification method-multiple annealing and looping-based amplification cycles-to phase the personal genome and map recombination events at high resolution, which are nonuniformly distributed across the genome in the absence of selection pressure. The paucity of recombination near transcription start sites observed in individual sperm indicates that such a phenomenon is intrinsic to the molecular mechanism of meiosis. Interestingly, a decreased crossover frequency combined with an increase of autosomal aneuploidy is observable on a global per-sperm basis.
Topics: Aneuploidy; Chromosome Segregation; Chromosomes, Human; Crossing Over, Genetic; Genome, Human; Haplotypes; Heterozygote; High-Throughput Nucleotide Sequencing; Humans; Male; Meiosis; Middle Aged; Nucleic Acid Amplification Techniques; Recombination, Genetic; Sequence Analysis, DNA; Single-Cell Analysis; Spermatozoa; Transcription Initiation Site
PubMed: 23258895
DOI: 10.1126/science.1229112 -
Proceedings of the National Academy of... Nov 1995Recent studies of Saccharomyces cerevisiae have significantly advanced our understanding of the molecular mechanisms of meiotic chromosome behavior. Structural... (Review)
Review
Recent studies of Saccharomyces cerevisiae have significantly advanced our understanding of the molecular mechanisms of meiotic chromosome behavior. Structural components of the synaptonemal complex have been identified and studies of mutants defective in synapsis have provided insight into the role of the synaptonemal complex in homolog pairing, genetic recombination, crossover interference, and meiotic chromosome segregation. There is compelling evidence that most or all meiotic recombination events initiate with double-strand breaks. Several intermediates in the double-strand break repair pathway have been characterized and mutants blocked at different steps in the pathway have been identified. With the application of genetic, molecular, cytological, and biochemical methods in a single organism, we can expect an increasingly comprehensive and unified view of the meiotic process.
Topics: Chromosomes, Fungal; Crossing Over, Genetic; DNA Repair; Meiosis; Models, Genetic; Recombination, Genetic; Saccharomyces cerevisiae; Synaptonemal Complex
PubMed: 7479818
DOI: 10.1073/pnas.92.23.10450 -
Methods in Molecular Biology (Clifton,... 2009The fission yeast Schizosaccharomyces pombe is well-suited for studying meiotic recombination. Methods are described here for culturing S. pombe and for genetic assays... (Review)
Review
The fission yeast Schizosaccharomyces pombe is well-suited for studying meiotic recombination. Methods are described here for culturing S. pombe and for genetic assays ofintragenic recombination (gene conversion), intergenic recombination (crossing-over), and spore viability. Both random spore and tetrad analyses are described.
Topics: Cell Culture Techniques; Genetic Techniques; Meiosis; Models, Biological; Recombination, Genetic; Schizosaccharomyces; Spores, Fungal
PubMed: 19799177
DOI: 10.1007/978-1-59745-527-5_6 -
BioEssays : News and Reviews in... Dec 2010Studies in the yeast Saccharomyces cerevisiae have validated the major features of the double-strand break repair (DSBR) model as an accurate representation of the... (Review)
Review
Meiotic versus mitotic recombination: two different routes for double-strand break repair: the different functions of meiotic versus mitotic DSB repair are reflected in different pathway usage and different outcomes.
Studies in the yeast Saccharomyces cerevisiae have validated the major features of the double-strand break repair (DSBR) model as an accurate representation of the pathway through which meiotic crossovers (COs) are produced. This success has led to this model being invoked to explain double-strand break (DSB) repair in other contexts. However, most non-crossover (NCO) recombinants generated during S. cerevisiae meiosis do not arise via a DSBR pathway. Furthermore, it is becoming increasingly clear that DSBR is a minor pathway for recombinational repair of DSBs that occur in mitotically-proliferating cells and that the synthesis-dependent strand annealing (SDSA) model appears to describe mitotic DSB repair more accurately. Fundamental dissimilarities between meiotic and mitotic recombination are not unexpected, since meiotic recombination serves a very different purpose (accurate chromosome segregation, which requires COs) than mitotic recombination (repair of DNA damage, which typically generates NCOs).
Topics: Chromosome Segregation; Crossing Over, Genetic; DNA Breaks, Double-Stranded; DNA Damage; DNA Repair; Meiosis; Mitosis; Mutation; Recombination, Genetic; Saccharomyces cerevisiae
PubMed: 20967781
DOI: 10.1002/bies.201000087