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Molecules and Cells May 2022During meiosis, homologous chromosomes (homologs) pair and undergo genetic recombination via assembly and disassembly of the synaptonemal complex. Meiotic recombination... (Review)
Review
During meiosis, homologous chromosomes (homologs) pair and undergo genetic recombination via assembly and disassembly of the synaptonemal complex. Meiotic recombination is initiated by excess formation of DNA double-strand breaks (DSBs), among which a subset are repaired by reciprocal genetic exchange, called crossovers (COs). COs generate genetic variations across generations, profoundly affecting genetic diversity and breeding. At least one CO between homologs is essential for the first meiotic chromosome segregation, but generally only one and fewer than three inter-homolog COs occur in plants. CO frequency and distribution are biased along chromosomes, suppressed in centromeres, and controlled by pro-CO, anti-CO, and epigenetic factors. Accurate and high-throughput detection of COs is important for our understanding of CO formation and chromosome behavior. Here, we review advanced approaches that enable precise measurement of the location, frequency, and genomic landscapes of COs in plants, with a focus on .
Topics: Arabidopsis; Crossing Over, Genetic; DNA Breaks, Double-Stranded; Homologous Recombination; Meiosis; Plants
PubMed: 35444069
DOI: 10.14348/molcells.2022.2054 -
Methods in Molecular Biology (Clifton,... 2017Many morphological features, in both physical and biological systems, exhibit spatial patterns that are specifically characterized by a tendency to occur with even...
Many morphological features, in both physical and biological systems, exhibit spatial patterns that are specifically characterized by a tendency to occur with even spacing (in one, two, or three dimensions). The positions of crossover (CO) recombination events along meiotic chromosomes provide an interesting biological example of such an effect. In general, mechanisms that explain such patterns may (a) be mechanically based, (b) occur by a reaction-diffusion mechanism in which macroscopic mechanical effects are irrelevant, or (c) involve a combination of both types of effects. We have proposed that meiotic CO patterns arise by a mechanical mechanism, have developed mathematical expressions for such a process based on a particular physical system with analogous properties (the so-called beam-film model), and have shown that the beam-film model can very accurately explain experimental CO patterns as a function of the values of specific defined parameters. Importantly, the mathematical expressions of the beam-film model can apply quite generally to any mechanism, whether it involves mechanical components or not, as long as its logic and component features correspond to those of the beam-film system. Furthermore, via its various parameters, the beam-film model discretizes the patterning process into specific components. Thus, the model can be used to explore the theoretically predicted effects of various types of changes in the patterning process. Such predictions can expand detailed understanding of the bases for various biological effects. We present here a new MATLAB program that implements the mathematical expressions of the beam-film model with increased robustness and accessibility as compared to programs presented previously. As in previous versions, the presented program permits both (1) simulation of predicted CO positions along chromosomes of a test population and (2) easy analysis of CO positions, both for experimental data sets and for data sets resulting from simulations. The goal of the current presentation is to make these approaches more readily accessible to a wider audience of researchers. Also, the program is easily modified, and we encourage interested users to make changes to suit their specific needs. A link to the program is available on the Kleckner laboratory website: http://projects.iq.harvard.edu/kleckner_lab .
Topics: Chromosomes; Chromosomes, Human; Crossing Over, Genetic; Humans; Male; Meiosis; Models, Genetic; Recombination, Genetic; Software
PubMed: 28349405
DOI: 10.1007/978-1-4939-6340-9_18 -
Genetics Jun 2017Meiotic homologous recombination, a critical event for ensuring faithful chromosome segregation and creating genetic diversity, is initiated by programmed DNA...
Meiotic homologous recombination, a critical event for ensuring faithful chromosome segregation and creating genetic diversity, is initiated by programmed DNA double-strand breaks (DSBs) formed at recombination hotspots. Meiotic DSB formation is likely to be influenced by other DNA-templated processes including transcription, but how DSB formation and transcription interact with each other has not been understood well. In this study, we used fission yeast to investigate a possible interplay of these two events. A group of hotspots in fission yeast are associated with sequences similar to the cyclic AMP response element and activated by the ATF/CREB family transcription factor dimer Atf1-Pcr1. We first focused on one of those hotspots, , and Atf1. Our results showed that multiple transcripts, shorter than the full-length messenger RNA, emanate from a region surrounding the hotspot. Interestingly, we found that the previously known recombination-activation region of Atf1 is also a transactivation domain, whose deletion affected DSB formation and short transcript production at These results point to a possibility that the two events may be related to each other at In fact, comparison of published maps of meiotic transcripts and hotspots suggested that hotspots are very often located close to meiotically transcribed regions. These observations therefore propose that meiotic DSB formation in fission yeast may be connected to transcription of surrounding regions.
Topics: Activating Transcription Factor 1; Activating Transcription Factors; Cyclic AMP Response Element-Binding Protein; DNA Breaks, Double-Stranded; Homologous Recombination; Meiosis; Phosphoproteins; Recombination, Genetic; Schizosaccharomyces; Schizosaccharomyces pombe Proteins
PubMed: 28396503
DOI: 10.1534/genetics.116.197954 -
Genetics Mar 2022The number and placement of meiotic crossover events during meiosis have important implications for the fidelity of chromosome segregation as well as patterns of...
The number and placement of meiotic crossover events during meiosis have important implications for the fidelity of chromosome segregation as well as patterns of inheritance. Despite the functional importance of recombination, recombination landscapes vary widely among and within species, and this can have a strong impact on evolutionary processes. A good knowledge of recombination landscapes is important for model systems in evolutionary and ecological genetics, since it can improve interpretation of genomic patterns of differentiation and genome evolution, and provides an important starting point for understanding the causes and consequences of recombination rate variation. Arabidopsis arenosa is a powerful evolutionary genetic model for studying the molecular basis of adaptation and recombination rate evolution. Here, we generate genetic maps for 2 diploid A. arenosa individuals from distinct genetic lineages where we have prior knowledge that meiotic genes show evidence of selection. We complement the genetic maps with cytological approaches to map and quantify recombination rates, and test the idea that these populations might have distinct patterns of recombination. We explore how recombination differs at the level of populations, individuals, sexes and genomic regions. We show that the positioning of crossovers along a chromosome correlates with their number, presumably a consequence of crossover interference, and discuss how this effect can cause differences in recombination landscape among sexes or species. We identify several instances of female segregation distortion. We found that averaged genome-wide recombination rate is lower and sex differences subtler in A. arenosa than in Arabidopsis thaliana.
Topics: Arabidopsis; Chromosome Segregation; Crossing Over, Genetic; Diploidy; Female; Humans; Male; Meiosis; Recombination, Genetic
PubMed: 35100396
DOI: 10.1093/genetics/iyab236 -
Philosophical Transactions of the Royal... Dec 2017Meiotic recombination is necessary for successful gametogenesis in most sexually reproducing organisms and is a fundamental genomic parameter, influencing the efficacy... (Review)
Review
Meiotic recombination is necessary for successful gametogenesis in most sexually reproducing organisms and is a fundamental genomic parameter, influencing the efficacy of selection and the fate of new mutations. The molecular and evolutionary functions of recombination should impose strong selective constraints on the range of recombination rates. Yet, variation in recombination rate is observed on a variety of genomic and evolutionary scales. In the past decade, empirical studies have described variation in recombination rate within genomes, between individuals, between sexes, between populations and between species. At the same time, theoretical work has provided an increasingly detailed picture of the evolutionary advantages to recombination. Perhaps surprisingly, the causes of natural variation in recombination rate remain poorly understood. We argue that empirical and theoretical approaches to understand the evolution of recombination have proceeded largely independently of each other. Most models that address the evolution of recombination rate were created to explain the evolutionary advantage of recombination rather than quantitative differences in rate among individuals. Conversely, most empirical studies aim to describe variation in recombination rate, rather than to test evolutionary hypotheses. In this Perspective, we argue that efforts to integrate the rich bodies of empirical and theoretical work on recombination rate are crucial to moving this field forward. We provide new directions for the development of theory and the production of data that will jointly close this gap.This article is part of the themed issue 'Evolutionary causes and consequences of recombination rate variation in sexual organisms'.
Topics: Evolution, Molecular; Genome; Models, Genetic; Recombination, Genetic
PubMed: 29109228
DOI: 10.1098/rstb.2016.0469 -
Experimental Cell Research Nov 2014Meiotic recombination has two key functions: the faithful assortment of chromosomes into gametes and the creation of genetic diversity. Both processes require that... (Review)
Review
Meiotic recombination has two key functions: the faithful assortment of chromosomes into gametes and the creation of genetic diversity. Both processes require that meiotic recombination occurs between homologous chromosomes, rather than sister chromatids. Accordingly, a host of regulatory factors are activated during meiosis to distinguish sisters from homologs, suppress recombination between sister chromatids and promote the chromatids of the homologous chromosome as the preferred recombination partners. Here, we discuss the recent advances in our understanding of the mechanistic basis of meiotic recombination template choice, focusing primarily on developments in the budding yeast, Saccharomyces cerevisiae, where the regulation is currently best understood.
Topics: DNA Repair; Meiosis; Recombination, Genetic; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Sister Chromatid Exchange
PubMed: 25158281
DOI: 10.1016/j.yexcr.2014.08.024 -
Biochemical Society Transactions Aug 2022Wheat is a major cereal crop that possesses a large allopolyploid genome formed through hybridisation of tetraploid and diploid progenitors. During meiosis, crossovers... (Review)
Review
Wheat is a major cereal crop that possesses a large allopolyploid genome formed through hybridisation of tetraploid and diploid progenitors. During meiosis, crossovers (COs) are constrained in number to 1-3 per chromosome pair that are predominantly located towards the chromosome ends. This reduces the probability of advantageous traits recombining onto the same chromosome, thus limiting breeding. Therefore, understanding the underlying factors controlling meiotic recombination may provide strategies to unlock the genetic potential in wheat. In this mini-review, we will discuss the factors associated with restricted CO formation in wheat, such as timing of meiotic events, chromatin organisation, pre-meiotic DNA replication and dosage of CO genes, as a means to modulate recombination.
Topics: Chromosomes; Crossing Over, Genetic; Homologous Recombination; Meiosis; Triticum
PubMed: 35901450
DOI: 10.1042/BST20220405 -
PLoS Genetics Jun 2016In many mammals, including humans and mice, the zinc finger histone methyltransferase PRDM9 performs the first step in meiotic recombination by specifying the locations...
In many mammals, including humans and mice, the zinc finger histone methyltransferase PRDM9 performs the first step in meiotic recombination by specifying the locations of hotspots, the sites of genetic recombination. PRDM9 binds to DNA at hotspots through its zinc finger domain and activates recombination by trimethylating histone H3K4 on adjacent nucleosomes through its PR/SET domain. Recently, the isolated PR/SET domain of PRDM9 was shown capable of also trimethylating H3K36 in vitro, raising the question of whether this reaction occurs in vivo during meiosis, and if so, what its function might be. Here, we show that full-length PRDM9 does trimethylate H3K36 in vivo in mouse spermatocytes. Levels of H3K4me3 and H3K36me3 are highly correlated at hotspots, but mutually exclusive elsewhere. In vitro, we find that although PRDM9 trimethylates H3K36 much more slowly than it does H3K4, PRDM9 is capable of placing both marks on the same histone molecules. In accord with these results, we also show that PRDM9 can trimethylate both K4 and K36 on the same nucleosomes in vivo, but the ratio of K4me3/K36me3 is much higher for the pair of nucleosomes adjacent to the PRDM9 binding site compared to the next pair further away. Importantly, H3K4me3/H3K36me3-double-positive nucleosomes occur only in regions of recombination: hotspots and the pseudoautosomal (PAR) region of the sex chromosomes. These double-positive nucleosomes are dramatically reduced when PRDM9 is absent, showing that this signature is PRDM9-dependent at hotspots; the residual double-positive nucleosomes most likely come from the PRDM9-independent PAR. These results, together with the fact that PRDM9 is the only known mammalian histone methyltransferase with both H3K4 and H3K36 trimethylation activity, suggest that trimethylation of H3K36 plays an important role in the recombination process. Given the known requirement of H3K36me3 for double strand break repair by homologous recombination in somatic cells, we suggest that it may play the same role in meiosis.
Topics: Animals; Binding Sites; DNA Breaks, Double-Stranded; DNA Repair; Histone Methyltransferases; Histone-Lysine N-Methyltransferase; Histones; Homologous Recombination; Meiosis; Mice; Mice, Inbred C57BL; Nucleosomes; Recombination, Genetic; Zinc Fingers
PubMed: 27362481
DOI: 10.1371/journal.pgen.1006146 -
Cold Spring Harbor Perspectives in... Oct 2014The generation of haploid gametes by meiosis is a highly conserved process for sexually reproducing organisms that, in almost all cases, involves the extensive breakage... (Review)
Review
The generation of haploid gametes by meiosis is a highly conserved process for sexually reproducing organisms that, in almost all cases, involves the extensive breakage of chromosomes. These chromosome breaks occur during meiotic prophase and are essential for meiotic recombination as well as the subsequent segregation of homologous chromosomes. However, their formation and repair must be carefully monitored and choreographed with nuclear dynamics and the cell division program to avoid the creation of aberrant chromosomes and defective gametes. It is becoming increasingly clear that an intricate checkpoint-signaling network related to the canonical DNA damage response is deeply interwoven with the meiotic program and preserves order during meiotic prophase. This meiotic checkpoint network (MCN) creates a wide range of dependent relationships controlling chromosome movement, chromosome pairing, chromatin structure, and double-strand break (DSB) repair. In this review, we summarize our current understanding of the MCN. We discuss commonalities and differences in different experimental systems, with a particular emphasis on the emerging design principles that control and limit cross talk between signals to ultimately ensure the faithful inheritance of chromosomes by the next generation.
Topics: Apoptosis; Cell Cycle Checkpoints; Chromosome Pairing; DNA Breaks, Double-Stranded; DNA Repair; DNA Replication; Models, Genetic; Prophase; Recombination, Genetic; Signal Transduction
PubMed: 25274702
DOI: 10.1101/cshperspect.a016675 -
Genome Biology Nov 2021Intermixing of genomes through meiotic reassortment and recombination of homologous chromosomes is a unifying theme of sexual reproduction in eukaryotic organisms and is...
BACKGROUND
Intermixing of genomes through meiotic reassortment and recombination of homologous chromosomes is a unifying theme of sexual reproduction in eukaryotic organisms and is considered crucial for their adaptive evolution. Previous studies of the budding yeast species Saccharomycodes ludwigii suggested that meiotic crossing over might be absent from its sexual life cycle, which is predominated by fertilization within the meiotic tetrad.
RESULTS
We demonstrate that recombination is extremely suppressed during meiosis in Sd. ludwigii. DNA double-strand break formation by the conserved transesterase Spo11, processing and repair involving interhomolog interactions are required for normal meiosis but do not lead to crossing over. Although the species has retained an intact meiotic gene repertoire, genetic and population analyses suggest the exceptionally rare occurrence of meiotic crossovers in its genome. A strong AT bias of spontaneous mutations and the absence of recombination are likely responsible for its unusually low genomic GC level.
CONCLUSIONS
Sd. ludwigii has followed a unique evolutionary trajectory that possibly derives fitness benefits from the combination of frequent mating between products of the same meiotic event with the extreme suppression of meiotic recombination. This life style ensures preservation of heterozygosity throughout its genome and may enable the species to adapt to its environment and survive with only minimal levels of rare meiotic recombination. We propose Sd. ludwigii as an excellent natural forum for the study of genome evolution and recombination rates.
Topics: Chromosome Segregation; Crossing Over, Genetic; Evolution, Molecular; Genome, Fungal; Loss of Heterozygosity; Meiosis; Mitosis; Mutation Rate; Recombination, Genetic; Saccharomycetales
PubMed: 34732243
DOI: 10.1186/s13059-021-02521-w