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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 -
Current Topics in Developmental Biology 2023Sexually reproducing organisms produce haploid gametes through meiotic cell division, during which a single round of DNA replication is followed by two consecutive... (Review)
Review
Sexually reproducing organisms produce haploid gametes through meiotic cell division, during which a single round of DNA replication is followed by two consecutive chromosome segregation. A series of meiosis-specific events take place during the meiotic prophase to ensure successful chromosome segregation. These events include programmed DNA double-strand break formation, chromosome movement driven by cytoplasmic forces, homologous pairing, synaptonemal complex installation, and inter-homolog crossover formation. Phase separation has emerged as a key principle controlling cellular biomolecular material organization and biological processes. Recent studies have revealed the involvements of phase separation in assembling meiotic chromosome-associated structures. Here we review and discuss how phase separation may participate in meiotic chromosome dynamics and propose that it may provide opportunities to understand the mysteries in meiotic regulations.
Topics: Meiosis; Synaptonemal Complex; DNA Breaks, Double-Stranded; Chromosome Segregation
PubMed: 36681478
DOI: 10.1016/bs.ctdb.2022.04.004 -
Genes Jan 2022Meiosis is critically different from mitosis in that during meiosis, pairing and segregation of homologous chromosomes occur. During meiosis, the morphology of sister... (Review)
Review
Meiosis is critically different from mitosis in that during meiosis, pairing and segregation of homologous chromosomes occur. During meiosis, the morphology of sister chromatids changes drastically, forming a prominent axial structure in the synaptonemal complex. The meiosis-specific cohesin complex plays a central role in the regulation of the processes required for recombination. In particular, the Rec8 subunit of the meiotic cohesin complex, which is conserved in a wide range of eukaryotes, has been analyzed for its function in modulating chromosomal architecture during the pairing and recombination of homologous chromosomes in meiosis. Here, we review the current understanding of Rec8 cohesin as a structural platform for meiotic chromosomes.
Topics: Cell Cycle Proteins; Chromatids; Chromosomal Proteins, Non-Histone; Meiosis; Cohesins
PubMed: 35205245
DOI: 10.3390/genes13020200 -
Seminars in Cell & Developmental Biology Dec 2018In virtually all sexually reproducing animals, oocytes arrest in meiotic prophase and resume meiosis in a conserved biological process called meiotic maturation. Meiotic... (Review)
Review
In virtually all sexually reproducing animals, oocytes arrest in meiotic prophase and resume meiosis in a conserved biological process called meiotic maturation. Meiotic arrest enables oocytes, which are amongst the largest cells in an organism, to grow and accumulate the necessary cellular constituents required to support embryonic development. Oocyte arrest can be maintained for a prolonged period, up to 50 years in humans, and defects in the meiotic maturation process interfere with the faithful segregation of meiotic chromosomes, representing the leading cause of human birth defects and female infertility. Hormonal signaling and interactions with somatic cells of the gonad control the timing of oocyte meiotic maturation. Signaling activates the CDK1/cyclin B kinase, which plays a central role in regulating the nuclear and cytoplasmic events of meiotic maturation. Nuclear maturation encompasses nuclear envelope breakdown, meiotic spindle assembly, and chromosome segregation whereas cytoplasmic maturation involves major changes in oocyte protein translation and cytoplasmic organelles and is less well understood. Classically, meiotic maturation has been studied in organisms with large oocytes to facilitate biochemical analysis. Recently, the nematode Caenorhabditis elegans is emerging as a genetic paradigm for studying the regulation of oocyte meiotic maturation. Studies in this system have revealed conceptual, anatomical, and molecular links to oocytes in all animals including humans. This review focuses on the signaling mechanisms required to control oocyte growth and meiotic maturation in C. elegans and discusses how the downstream regulation of protein translation coordinates the completion of meiosis and the oocyte-to-embryo transition.
Topics: Animals; Caenorhabditis elegans; Embryonic Development; Humans; Meiosis; Oocytes; Oogenesis; Signal Transduction
PubMed: 29242146
DOI: 10.1016/j.semcdb.2017.12.005 -
Chromosoma Sep 2019Meiosis is the special division that produces haploid gametes, such as sperm and eggs. It involves a complex series of events that integrate large structural changes at...
Meiosis is the special division that produces haploid gametes, such as sperm and eggs. It involves a complex series of events that integrate large structural changes at the chromosome scale with fine regulation of recombination events in localized regions. To evaluate the complexity of these processes, the meiosis field covers a variety of disciplines and model organisms, making it an exciting and rapidly changing area of research. The field as a whole highlights both the conserved aspects of meiosis, as well as the marked diversity of the means taken to ensure that, ultimately, gametes will contain a balanced number of chromosomes and genetic diversity will have been produced. Studying meiosis is also critically important for the improvement of our human condition as errors of meiosis are a leading cause of infertility, miscarriage, and developmental disabilities. Finally, the complex chromosome behavior of meiosis is a genetically tractable paradigm, the study of which improves our understanding of many fundamental cellular processes including DNA repair, genome stability, cancer etiology, chromatin structure, and chromosome dynamics.This special issue on meiosis contains twenty-two papers, of which five are in-depth reviews that complement and put in context the experimental data presented in the seventeen original research articles. The content of this issue illustrates the diversity of topics covered by researchers in the field, ranging from the effects of environment and external factors on the success of meiosis, the cell cycle actors that control the meiotic divisions, the mechanism of chromosome segregation, and the mechanisms that ensure proper homologous chromosome pairing, recombination, and synapsis. Multiple organisms are covered. Also evident is the fact that more and more studies use multicellular organisms as a model system, in large part due to the increased availability of tools that were previously restricted to studies in budding and fission yeasts.
Topics: Animals; Chromosome Segregation; DNA Replication; Humans; Meiosis
PubMed: 31616989
DOI: 10.1007/s00412-019-00726-4 -
Nature Reviews. Genetics May 2024Sexually reproducing eukaryotes use recombination between homologous chromosomes to promote chromosome segregation during meiosis. Meiotic recombination is almost... (Review)
Review
Sexually reproducing eukaryotes use recombination between homologous chromosomes to promote chromosome segregation during meiosis. Meiotic recombination is almost universally conserved in its broad strokes, but specific molecular details often differ considerably between taxa, and the proteins that constitute the recombination machinery show substantial sequence variability. The extent of this variation is becoming increasingly clear because of recent increases in genomic resources and advances in protein structure prediction. We discuss the tension between functional conservation and rapid evolutionary change with a focus on the proteins that are required for the formation and repair of meiotic DNA double-strand breaks. We highlight phylogenetic relationships on different time scales and propose that this remarkable evolutionary plasticity is a fundamental property of meiotic recombination that shapes our understanding of molecular mechanisms in reproductive biology.
Topics: DNA Repair; Phylogeny; Homologous Recombination; Meiosis; DNA Breaks, Double-Stranded
PubMed: 38036793
DOI: 10.1038/s41576-023-00669-8 -
Trends in Genetics : TIG May 2017Rates of meiotic recombination are widely variable both within and among species. However, the functional significance of this variation remains largely unknown. Is the... (Review)
Review
Rates of meiotic recombination are widely variable both within and among species. However, the functional significance of this variation remains largely unknown. Is the observed within-species variation in recombination rate adaptive? Recent work has revealed new insight into the scale and scope of population-level variation in recombination rate. These data indicate that the magnitude of within-population variation in recombination is similar among taxa. The apparent similarity of the variance in recombination rate among individuals between distantly related species suggests that the relative costs and benefits of recombination that establish the upper and lower bounds may be similar across species. Here we review the current data on intraspecific variation in recombination rate and discuss the molecular and evolutionary costs and benefits of recombination frequency. We place this variation in the context of adaptation and highlight the need for more empirical studies focused on the adaptive value of variation in recombination rate.
Topics: Animals; Evolution, Molecular; Genetic Variation; Humans; Meiosis; Recombination, Genetic
PubMed: 28359582
DOI: 10.1016/j.tig.2017.03.003 -
Annual Review of Genetics Nov 2021Sex, as well as meiotic recombination between homologous chromosomes, is nearly ubiquitous among eukaryotes. In those species that use it, recombination is important for... (Review)
Review
Sex, as well as meiotic recombination between homologous chromosomes, is nearly ubiquitous among eukaryotes. In those species that use it, recombination is important for chromosome segregation during gamete production, and thus for fertility. Strikingly, although in most species only one crossover event per chromosome is required to ensure proper segregation, recombination rates vary considerably above this minimum and show variation within and among species. However, whether this variation in recombination is adaptive or neutral and what might shape it remain unclear. Empirical studies and theory support the idea that recombination is generally beneficial but can also have costs. Here, we review variation in genome-wide recombination rates, explore what might cause this, and discuss what is known about its mechanistic basis. We end by discussing the environmental sensitivity of meiosis and recombination rates, how these features may relate to adaptation, and their implications for a broader understanding of recombination rate evolution.
Topics: Chromosome Segregation; Chromosomes; Genome; Homologous Recombination; Meiosis
PubMed: 34310193
DOI: 10.1146/annurev-genet-021721-033821 -
Trends in Genetics : TIG Jun 2018Unbiased allele transmission into progeny is a fundamental genetic concept canonized as Mendel's Law of Segregation. Not all alleles, however, abide by the law. Killer... (Review)
Review
Unbiased allele transmission into progeny is a fundamental genetic concept canonized as Mendel's Law of Segregation. Not all alleles, however, abide by the law. Killer meiotic drivers are ultra-selfish DNA sequences that are transmitted into more than half (sometimes all) of the meiotic products generated by a heterozygote. As their name implies, these loci gain a transmission advantage in heterozygotes by destroying otherwise viable meiotic products that do not inherit the driver. We review and classify killer meiotic drive genes across a wide spectrum of eukaryotes. We discuss how analyses of these ultra-selfish genes can lead to greater insight into the mechanisms of gametogenesis and the causes of infertility.
Topics: Alleles; Chromosome Segregation; Eukaryota; Genetics; Heterozygote; Meiosis
PubMed: 29499907
DOI: 10.1016/j.tig.2018.02.003 -
Biological Reviews of the Cambridge... Jun 2021The separation of germ cell populations from the soma is part of the evolutionary transition to multicellularity. Only genetic information present in the germ cells will... (Review)
Review
The separation of germ cell populations from the soma is part of the evolutionary transition to multicellularity. Only genetic information present in the germ cells will be inherited by future generations, and any molecular processes affecting the germline genome are therefore likely to be passed on. Despite its prevalence across taxonomic kingdoms, we are only starting to understand details of the underlying micro-evolutionary processes occurring at the germline genome level. These include segregation, recombination, mutation and selection and can occur at any stage during germline differentiation and mitotic germline proliferation to meiosis and post-meiotic gamete maturation. Selection acting on germ cells at any stage from the diploid germ cell to the haploid gametes may cause significant deviations from Mendelian inheritance and may be more widespread than previously assumed. The mechanisms that affect and potentially alter the genomic sequence and allele frequencies in the germline are pivotal to our understanding of heritability. With the rise of new sequencing technologies, we are now able to address some of these unanswered questions. In this review, we comment on the most recent developments in this field and identify current gaps in our knowledge.
Topics: Biological Evolution; Genome; Germ Cells; Meiosis; Mutation
PubMed: 33615674
DOI: 10.1111/brv.12680