-
Critical Reviews in Eukaryotic Gene... 2018Traditional methods for analyzing meiotic recombination in humans are limited. Recently developed in vitro and in silico assays together are useful for confirmation and... (Review)
Review
Traditional methods for analyzing meiotic recombination in humans are limited. Recently developed in vitro and in silico assays together are useful for confirmation and detection of meiotic recombination hotspots from population polymorphism data. These techniques are significant both for understanding the nature of human meiotic recombination and for applications such as association studies.
Topics: DNA Breaks, Double-Stranded; Genetic Association Studies; Genetic Variation; Humans; Meiosis; Polymorphism, Single Nucleotide; Recombination, Genetic
PubMed: 30311567
DOI: 10.1615/CritRevEukaryotGeneExpr.2018024602 -
Molecules and Cells Nov 2017Meiotic homologous recombination generates new combinations of preexisting genetic variation and is a crucial process in plant breeding. Within the last decade, our... (Review)
Review
Meiotic homologous recombination generates new combinations of preexisting genetic variation and is a crucial process in plant breeding. Within the last decade, our understanding of plant meiotic recombination and genome diversity has advanced considerably. Innovation in DNA sequencing technology has led to the exploration of high-resolution genetic and epigenetic information in plant genomes, which has helped to accelerate plant breeding practices via high-throughput genotyping, and linkage and association mapping. In addition, great advances toward understanding the genetic and epigenetic control mechanisms of meiotic recombination have enabled the expansion of breeding programs and the unlocking of genetic diversity that can be used for crop improvement. This review highlights the recent literature on plant meiotic recombination and discusses the translation of this knowledge to the manipulation of meiotic recombination frequency and location with regards to crop plant breeding.
Topics: Arabidopsis; CRISPR-Cas Systems; Chromosomes, Plant; Epigenesis, Genetic; Genetic Variation; Homologous Recombination; Meiosis; Plant Breeding
PubMed: 29179262
DOI: 10.14348/molcells.2017.0171 -
BioEssays : News and Reviews in... Aug 2023Meiotic recombination is one of the main sources of genetic variation, a fundamental factor in the evolutionary adaptation of sexual eukaryotes. Yet, the role of... (Review)
Review
Meiotic recombination is one of the main sources of genetic variation, a fundamental factor in the evolutionary adaptation of sexual eukaryotes. Yet, the role of variation in recombination rate and other recombination features remains underexplored. In this review, we focus on the sensitivity of recombination rates to different extrinsic and intrinsic factors. We briefly present the empirical evidence for recombination plasticity in response to environmental perturbations and/or poor genetic background and discuss theoretical models developed to explain how such plasticity could have evolved and how it can affect important population characteristics. We highlight a gap between the evidence, which comes mostly from experiments with diploids, and theory, which typically assumes haploid selection. Finally, we formulate open questions whose solving would help to outline conditions favoring recombination plasticity. This will contribute to answering the long-standing question of why sexual recombination exists despite its costs, since plastic recombination may be evolutionary advantageous even in selection regimes rejecting any non-zero constant recombination.
Topics: Recombination, Genetic; Prospective Studies; Eukaryota; Meiosis; Biological Evolution; Selection, Genetic
PubMed: 37246937
DOI: 10.1002/bies.202200237 -
Critical Reviews in Eukaryotic Gene... 2018Meiotic recombination plays a key role in reshuffling haplotypes in human populations and thus affects evolution profoundly. However, our understanding of recombination... (Review)
Review
Meiotic recombination plays a key role in reshuffling haplotypes in human populations and thus affects evolution profoundly. However, our understanding of recombination dynamics is largely limited to descriptions of variation in populations and families. Higher-resolution analysis (≤ 0.0001 cM) of de novo recombination events in human sperm DNA has revealed clustering into very narrow hotspots (1-2 kb) that generally coincide with abrupt breakdown of linkage disequilibrium. Recent findings have highlighted an unexpected molecular control of the distribution of meiotic double-strand breaks (DSBs) in mammals by a rapidly evolving gene in trans, PR-domain-containing 9 (PRDM9), and specific DNA sequence motifs in cis. In addition, the understanding of new regulators in DSB repair processes has allowed the delineation of recombination pathways that have two major outcomes, cross-overs and non-cross-overs, which have distinct mechanistic roles and consequences for genome evolution. Further molecular studies are needed to gain information about how hotspots originate, function, and evolve.
Topics: DNA Breaks, Double-Stranded; Gene Expression Regulation; Genome, Human; Histone-Lysine N-Methyltransferase; Humans; Linkage Disequilibrium; Male; Meiosis; Nucleotide Motifs; Recombination, Genetic; Spermatozoa
PubMed: 30311566
DOI: 10.1615/CritRevEukaryotGeneExpr.2018024601 -
Cell Aug 2021Genetic recombination generates novel trait combinations, and understanding how recombination is distributed across the genome is key to modern genetics. The PRDM9...
Genetic recombination generates novel trait combinations, and understanding how recombination is distributed across the genome is key to modern genetics. The PRDM9 protein defines recombination hotspots; however, megabase-scale recombination patterning is independent of PRDM9. The single round of DNA replication, which precedes recombination in meiosis, may establish these patterns; therefore, we devised an approach to study meiotic replication that includes robust and sensitive mapping of replication origins. We find that meiotic DNA replication is distinct; reduced origin firing slows replication in meiosis, and a distinctive replication pattern in human males underlies the subtelomeric increase in recombination. We detected a robust correlation between replication and both contemporary and historical recombination and found that replication origin density coupled with chromosome size determines the recombination potential of individual chromosomes. Our findings and methods have implications for understanding the mechanisms underlying DNA replication, genetic recombination, and the landscape of mammalian germline variation.
Topics: Animals; Base Composition; Chromosomes, Mammalian; DNA Breaks, Double-Stranded; DNA Replication; Genome; Germ Cells; Homologous Recombination; Humans; Male; Mammals; Meiosis; Mice; Replication Origin; S Phase; Telomere; Testis
PubMed: 34260899
DOI: 10.1016/j.cell.2021.06.025 -
The Plant Journal : For Cell and... Jul 2015During meiosis homologous chromosomes pair and undergo reciprocal genetic exchange, termed crossover. Meiotic recombination has a profound effect on patterns of genetic... (Review)
Review
During meiosis homologous chromosomes pair and undergo reciprocal genetic exchange, termed crossover. Meiotic recombination has a profound effect on patterns of genetic variation and is an important tool during crop breeding. Crossovers initiate from programmed DNA double-stranded breaks that are processed to form single-stranded DNA, which can invade a homologous chromosome. Strand invasion events mature into double Holliday junctions that can be resolved as crossovers. Extensive variation in the frequency of meiotic recombination occurs along chromosomes and is typically focused in narrow hotspots, observed both at the level of DNA breaks and final crossovers. We review methodologies to profile hotspots at different steps of the meiotic recombination pathway that have been used in different eukaryote species. We then discuss what these studies have revealed concerning specification of hotspot locations and activity and the contributions of both genetic and epigenetic factors. Understanding hotspots is important for interpreting patterns of genetic variation in populations and how eukaryotic genomes evolve. In addition, manipulation of hotspots will allow us to accelerate crop breeding, where meiotic recombination distributions can be limiting.
Topics: Crossing Over, Genetic; DNA Breaks, Double-Stranded; DNA, Single-Stranded; Epigenesis, Genetic; Fungi; Genetic Techniques; Genome; Homologous Recombination; Meiosis; Plants
PubMed: 25925869
DOI: 10.1111/tpj.12870 -
Yeast (Chichester, England) May 2017DNA helicases are ATP-driven motor proteins which translocate along DNA capable of dismantling DNA-DNA interactions and/or removing proteins bound to DNA. These... (Review)
Review
DNA helicases are ATP-driven motor proteins which translocate along DNA capable of dismantling DNA-DNA interactions and/or removing proteins bound to DNA. These biochemical capabilities make DNA helicases main regulators of crucial DNA metabolic processes, including DNA replication, DNA repair, and genetic recombination. This budding topic will focus on reviewing the function of DNA helicases important for homologous recombination during meiosis, and discuss recent advances in how these modulators of meiotic recombination are themselves regulated. The emphasis is placed on work in the two model yeasts, Saccharomyces cerevisiae and Schizosaccharomyces pombe, which has vastly expanded our understanding of meiotic homologous recombination, a process whose correct execution is instrumental for healthy gamete formation, and thus functioning sexual reproduction. Copyright © 2016 John Wiley & Sons, Ltd.
Topics: DNA Helicases; Homologous Recombination; Meiosis; Saccharomyces cerevisiae; Schizosaccharomyces
PubMed: 27930825
DOI: 10.1002/yea.3227 -
Science China. Life Sciences Mar 2015Meiotic recombination is a deeply conserved process within eukaryotes that has a profound effect on patterns of natural genetic variation. During meiosis homologous... (Review)
Review
Meiotic recombination is a deeply conserved process within eukaryotes that has a profound effect on patterns of natural genetic variation. During meiosis homologous chromosomes pair and undergo DNA double strand breaks generated by the Spo11 endonuclease. These breaks can be repaired as crossovers that result in reciprocal exchange between chromosomes. The frequency of recombination along chromosomes is highly variable, for example, crossovers are rarely observed in heterochromatin and the centromeric regions. Recent work in plants has shown that crossover hotspots occur in gene promoters and are associated with specific chromatin modifications, including H2A.Z. Meiotic chromosomes are also organized in loop-base arrays connected to an underlying chromosome axis, which likely interacts with chromatin to organize patterns of recombination. Therefore, epigenetic information exerts a major influence on patterns of meiotic recombination along chromosomes, genetic variation within populations and evolution of plant genomes.
Topics: Chromatin; Crossing Over, Genetic; Epigenesis, Genetic; Meiosis; Plants; Recombination, Genetic
PubMed: 25651968
DOI: 10.1007/s11427-015-4811-x -
Science (New York, N.Y.) Dec 2023Meiotic recombination commences with hundreds of programmed DNA breaks; however, the degree to which they are accurately repaired remains poorly understood. We report...
Meiotic recombination commences with hundreds of programmed DNA breaks; however, the degree to which they are accurately repaired remains poorly understood. We report that meiotic break repair is eightfold more mutagenic for single-base substitutions than was previously understood, leading to de novo mutation in one in four sperm and one in 12 eggs. Its impact on indels and structural variants is even higher, with 100- to 1300-fold increases in rates per break. We uncovered new mutational signatures and footprints relative to break sites, which implicate unexpected biochemical processes and error-prone DNA repair mechanisms, including translesion synthesis and end joining in meiotic break repair. We provide evidence that these mechanisms drive mutagenesis in human germ lines and lead to disruption of hundreds of genes genome wide.
Topics: Humans; Male; DNA Breaks, Double-Stranded; DNA Repair; Genome, Human; Meiosis; Mutagenesis; Mutation; Ovum; Recombination, Genetic; Semen; Translesion DNA Synthesis; Female
PubMed: 38033082
DOI: 10.1126/science.adh2531 -
Philosophical Transactions of the Royal... Dec 2017Recombination promotes genomic integrity among cells and tissues through double-strand break repair, and is critical for gamete formation and fertility through a strict... (Review)
Review
Recombination promotes genomic integrity among cells and tissues through double-strand break repair, and is critical for gamete formation and fertility through a strict regulation of the molecular mechanisms associated with proper chromosomal disjunction. In humans, congenital defects and recurrent structural abnormalities can be attributed to aberrant meiotic recombination. Moreover, mutations affecting genes involved in recombination pathways are directly linked to pathologies including infertility and cancer. Recombination is among the most prominent mechanism shaping genome variation, and is associated with not only the structuring of genomic variability, but is also tightly linked with the purging of deleterious mutations from populations. Together, these observations highlight the multiple roles of recombination in human genetics: its ability to act as a major force of evolution, its molecular potential to maintain genome repair and integrity in cell division and its mutagenic cost impacting disease evolution.This article is part of the themed issue 'Evolutionary causes and consequences of recombination rate variation in sexual organisms'.
Topics: Communicable Diseases; Evolution, Molecular; Genetic Linkage; Histone-Lysine N-Methyltransferase; Humans; Mutation; Recombination, Genetic
PubMed: 29109227
DOI: 10.1098/rstb.2016.0465