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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 -
European Journal of Medical Genetics Feb 2020Genomic instability is widespread during early embryo development. Aneuploidy, mosaicism, and copy number variants (CNVs) commonly appear in human preimplantation... (Review)
Review
Genomic instability is widespread during early embryo development. Aneuploidy, mosaicism, and copy number variants (CNVs) commonly appear in human preimplantation embryos. Both age-dependent meiotic aneuploidy and age-independent mitotic aneuploidy and CNVs occur In human embryos. Telomere attrition, which contributes to genomic instability in somatic cells, also may promote genomic instability in preimplantation embryos. Telomere dynamics during gametogenesis are strikingly dimorphic between females and males. Sperm telomeres lengthen with advancing paternal age, while oocyte telomeres are among the shortest in the body. Spermatogonia express telomerase activity throughout the life of the male, while oocytes and cleavage stage embryos express low or un-measureable levels of telomerase activity. Telomere attrition in oocytes contributes to meiotic dysfunction, including spindle dysmorphologies, reduced synapsis and chiasmata, as well as delayed, arrested and fragmented embryos. Cleavage stage embryos, with such inefficient telomere reconstitution, likely undergo NHEJ, which produces anaphase lag, chromosome bridges, micronuclei, and genomic instability, including mosaicism and CNVs. Cleavage stage embryos reconstitute the short telomeres inherited from their mothers by Alternative Lengthening of Telomeres (ALT), a DNA recombination based method involving RAD 50, MRE 11, Werner and Bloom proteins, as well as telomere sister chromatid exchange. ALT robustly reconstitutes telomeres, but also predisposes to genomic instability.
Topics: Animals; Chromosome Aberrations; Embryonic Development; Genomic Instability; Humans; Oocytes; Recombination, Genetic; Telomere
PubMed: 30862510
DOI: 10.1016/j.ejmg.2019.03.002 -
Seminars in Cell & Developmental Biology Jun 2016During the first division of meiosis, segregation of homologous chromosomes reduces the chromosome number by half. In most species, sister chromatid cohesion and... (Review)
Review
During the first division of meiosis, segregation of homologous chromosomes reduces the chromosome number by half. In most species, sister chromatid cohesion and reciprocal recombination (crossing-over) between homologous chromosomes are essential to provide tension to signal proper chromosome segregation during the first meiotic division. Crossovers are not distributed uniformly throughout the genome and are repressed at and near the centromeres. Rare crossovers that occur too near or in the centromere interfere with proper segregation and can give rise to aneuploid progeny, which can be severely defective or inviable. We review here how crossing-over occurs and how it is prevented in and around the centromeres. Molecular mechanisms of centromeric repression are only now being elucidated. However, rapid advances in understanding crossing-over, chromosome structure, and centromere functions promise to explain how potentially deleterious crossovers are avoided in certain chromosomal regions while allowing beneficial crossovers in others.
Topics: Animals; Centromere; Chromosome Segregation; DNA Breaks, Double-Stranded; Gene Conversion; Humans; Meiosis; Recombination, Genetic
PubMed: 26849908
DOI: 10.1016/j.semcdb.2016.01.042 -
ELife Aug 2017Synonymous codon usage (SCU) varies widely among human genes. In particular, genes involved in different functional categories display a distinct codon usage, which was...
Synonymous codon usage (SCU) varies widely among human genes. In particular, genes involved in different functional categories display a distinct codon usage, which was interpreted as evidence that SCU is adaptively constrained to optimize translation efficiency in distinct cellular states. We demonstrate here that SCU is not driven by constraints on tRNA abundance, but by large-scale variation in GC-content, caused by meiotic recombination, via the non-adaptive process of GC-biased gene conversion (gBGC). Expression in meiotic cells is associated with a strong decrease in recombination within genes. Differences in SCU among functional categories reflect differences in levels of meiotic transcription, which is linked to variation in recombination and therefore in gBGC. Overall, the gBGC model explains 70% of the variance in SCU among genes. We argue that the strong heterogeneity of SCU induced by gBGC in mammalian genomes precludes any optimization of the tRNA pool to the demand in codon usage.
Topics: Base Composition; Codon; Gene Conversion; Genetic Code; Genetic Variation; Genome, Human; Humans; Meiosis; Models, Genetic; RNA, Transfer
PubMed: 28826480
DOI: 10.7554/eLife.27344 -
BMC Genomics Jan 2017Meiotic recombination is a major source of genetic variation in eukaryotes. The role of recombination in evolution is recognized but little is known about how...
BACKGROUND
Meiotic recombination is a major source of genetic variation in eukaryotes. The role of recombination in evolution is recognized but little is known about how evolutionary forces affect the recombination pathway itself. Although the recombination pathway is fundamentally conserved across different species, genetic variation in recombination components and outcomes has been observed. Theoretical predictions and empirical studies suggest that changes in the recombination pathway are likely to provide adaptive abilities to populations experiencing directional or strong selection pressures, such as those occurring during species domestication. We hypothesized that adaptive changes in recombination may be associated with adaptive evolution patterns of genes involved in meiotic recombination.
RESULTS
To examine how maize evolution and domestication affected meiotic recombination genes, we studied patterns of sequence polymorphism and divergence in eleven genes controlling key steps in the meiotic recombination pathway in a diverse set of maize inbred lines and several accessions of teosinte, the wild ancestor of maize. We discovered that, even though the recombination genes generally exhibited high sequence conservation expected in a pathway controlling a key cellular process, they showed substantial levels and diverse patterns of sequence polymorphism. Among others, we found differences in sequence polymorphism patterns between tropical and temperate maize germplasms. Several recombination genes displayed patterns of polymorphism indicative of adaptive evolution.
CONCLUSIONS
Despite their ancient origin and overall sequence conservation, meiotic recombination genes can exhibit extensive and complex patterns of molecular evolution. Changes in these genes could affect the functioning of the recombination pathway, and may have contributed to the successful domestication of maize and its expansion to new cultivation areas.
Topics: Environment; Evolution, Molecular; Gene Duplication; Gene-Environment Interaction; Genes, Plant; Genetic Variation; Genome, Plant; Genomics; Inbreeding; Meiosis; Recombination, Genetic; Selection, Genetic; Zea mays
PubMed: 28122517
DOI: 10.1186/s12864-017-3486-z -
The Plant Cell Apr 2020
Topics: Arabidopsis; Crossing Over, Genetic; Meiosis
PubMed: 32111667
DOI: 10.1105/tpc.20.00162 -
Cytogenetic and Genome Research 2016Meiotic recombination is a process that increases genetic diversity and is fundamental for sexual reproduction. Determining by which mechanisms genetic variation is... (Review)
Review
Meiotic recombination is a process that increases genetic diversity and is fundamental for sexual reproduction. Determining by which mechanisms genetic variation is generated and maintained across different phylogenetic groups provides the basis for our understanding of biodiversity and evolution. In this review, we go through different aspects of this essential phenomenon, paying special attention to mammals. We provide a comprehensive view on the organization of meiotic chromosomes and the mechanisms involved in the formation and genomic distribution of recombination hotspots, focusing on the factors influencing the formation and repair of the massive amount of self-induced DNA breaks in early stages of meiosis. At the same time, we discuss the genetic and mechanistic factors that influence recombination landscapes in mammals, as reflected by several layers of regulation. These factors include the selective forces that affect the DNA sequence itself, which can be modulated by genome reshuffling and the evolutionary history of each taxon, and the forces that control how the DNA is packaged into chromosomes during meiosis.
Topics: Animals; Chromosomes, Mammalian; Crossing Over, Genetic; Evolution, Molecular; Homologous Recombination; Humans; Mammals; Meiosis
PubMed: 27926907
DOI: 10.1159/000452822 -
Genetics Oct 2023Meiosis is a specialized cell division program that is essential for sexual reproduction. The two meiotic divisions reduce chromosome number by half, typically...
Meiosis is a specialized cell division program that is essential for sexual reproduction. The two meiotic divisions reduce chromosome number by half, typically generating haploid genomes that are packaged into gametes. To achieve this ploidy reduction, meiosis relies on highly unusual chromosomal processes including the pairing of homologous chromosomes, assembly of the synaptonemal complex, programmed formation of DNA breaks followed by their processing into crossovers, and the segregation of homologous chromosomes during the first meiotic division. These processes are embedded in a carefully orchestrated cell differentiation program with multiple interdependencies between DNA metabolism, chromosome morphogenesis, and waves of gene expression that together ensure the correct number of chromosomes is delivered to the next generation. Studies in the budding yeast Saccharomyces cerevisiae have established essentially all fundamental paradigms of meiosis-specific chromosome metabolism and have uncovered components and molecular mechanisms that underlie these conserved processes. Here, we provide an overview of all stages of meiosis in this key model system and highlight how basic mechanisms of genome stability, chromosome architecture, and cell cycle control have been adapted to achieve the unique outcome of meiosis.
Topics: Recombination, Genetic; Saccharomycetales; Meiosis; Saccharomyces cerevisiae; Synaptonemal Complex
PubMed: 37616582
DOI: 10.1093/genetics/iyad125