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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 -
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 -
Trends in Cell Biology Apr 2021Phase separation has emerged as a new key principle of intracellular organization. Phase-separated structures play diverse roles in various biological processes and... (Review)
Review
Phase separation has emerged as a new key principle of intracellular organization. Phase-separated structures play diverse roles in various biological processes and pathogenesis of protein aggregation diseases. Recent work has revealed crucial functions for phase separation during germline development. Phase separation controls the assembly and segregation of germ granules that determine which embryonic cells become germ cells. Phase separation promotes the formation of the Balbiani body, a structure that stores organelles and RNAs during the prolonged prophase arrest of oocytes. Phase separation also facilitates meiotic recombination that prepares homologous chromosomes for segregation, and drives the formation of a liquid-like spindle domain that promotes spindle assembly in mammalian oocytes. We review how phase separation drives these essential steps during germline development.
Topics: Animals; Germ Cell Ribonucleoprotein Granules; Germ Cells; Homologous Recombination; Meiosis; Oocytes
PubMed: 33455855
DOI: 10.1016/j.tcb.2020.12.004 -
Journal of Molecular Cell Biology Sep 2022Meiosis is essential for evolution and genetic diversity in almost all sexual eukaryotic organisms. The mechanisms of meiotic recombination, such as synapsis, have been...
Meiosis is essential for evolution and genetic diversity in almost all sexual eukaryotic organisms. The mechanisms of meiotic recombination, such as synapsis, have been extensively investigated. However, it is still unclear whether signals from the cytoplasm or even from outside of the cell can regulate the meiosis process. Cilia are microtubule-based structures that protrude from the cell surface and function as signaling hubs to sense extracellular signals. Here, we reported an unexpected and critical role of cilia during meiotic recombination. During gametogenesis of zebrafish, cilia were specifically present in the prophase stages of both primary spermatocytes and primary oocytes. By developing a germ cell-specific CRISPR/Cas9 system, we demonstrated that germ cell-specific depletion of ciliary genes resulted in compromised double-strand break repair, reduced crossover formation, and increased germ cell apoptosis. Our study reveals a previously undiscovered role for cilia during meiosis and suggests that extracellular signals may regulate meiotic recombination via this particular organelle.
Topics: Animals; Male; Zebrafish; Cilia; Meiosis; Chromosome Pairing; DNA Repair
PubMed: 35981808
DOI: 10.1093/jmcb/mjac049 -
Cytogenetic and Genome Research 2016The cytological analysis of meiotic chromosomes is an exceptional tool to approach complex processes such as synapsis and recombination during the division. Chromosome... (Review)
Review
The cytological analysis of meiotic chromosomes is an exceptional tool to approach complex processes such as synapsis and recombination during the division. Chromosome studies of meiosis have been especially valuable in birds, where naturally occurring mutants or experimental knock-out animals are not available to fully investigate the basic mechanisms of major meiotic events. This review highlights the main contributions of synaptonemal complex and lampbrush chromosome research to the current knowledge of avian meiosis, with special emphasis on the organization of chromosomes during prophase I, the impact of chromosome rearrangements during meiosis, and distinctive features of the ZW pair.
Topics: Animals; Birds; Crossing Over, Genetic; Female; Genetic Markers; Meiosis; Meiotic Prophase I; Sex Chromosomes; Synaptonemal Complex
PubMed: 28030854
DOI: 10.1159/000453541 -
Cell Research May 2017Targeted proteolysis plays an important role in the execution and regulation of many cellular events. Two recent papers in Science identify novel roles for...
Targeted proteolysis plays an important role in the execution and regulation of many cellular events. Two recent papers in Science identify novel roles for proteasome-mediated proteolysis in homologous chromosome pairing, recombination, and segregation during meiosis.
Topics: Chromosome Pairing; Chromosomes; Meiosis; Proteasome Endopeptidase Complex; Recombination, Genetic
PubMed: 28266542
DOI: 10.1038/cr.2017.28 -
Journal of Genetics 2022Gerrymandering, the structuring of voting districts to favour certain politicians and political groups, undermines fair elections and presents a serious challenge to...
Gerrymandering, the structuring of voting districts to favour certain politicians and political groups, undermines fair elections and presents a serious challenge to democracy. We introduce a solution to gerrymandering inspired by the biological process of cell division in sexually reproducing organisms, meiosis, in which the boundaries of electorates are frequently redrawn by randomizing algorithms. By demonstrating the deep parallels between meiosis and John Rawls's concept of a 'veil of ignorance', we also show how one of the biggest threats to the integrity of meiosis-selfish genetic elements, genes that promote their own transmission at the expense of organismal fitness-can inspire another potential advantage to frequent random redistricting.
Topics: Meiosis; Politics
PubMed: 36156509
DOI: No ID Found -
Current Biology : CB Aug 2008
Topics: Animals; Chromosome Disorders; Chromosome Segregation; Humans; Meiosis; Recombination, Genetic
PubMed: 18682199
DOI: 10.1016/j.cub.2008.06.013 -
Annual Review of Genomics and Human... Aug 2023In meiosis, homologous chromosome synapsis is mediated by a supramolecular protein structure, the synaptonemal complex (SC), that assembles between homologous chromosome... (Review)
Review
In meiosis, homologous chromosome synapsis is mediated by a supramolecular protein structure, the synaptonemal complex (SC), that assembles between homologous chromosome axes. The mammalian SC comprises at least eight largely coiled-coil proteins that interact and self-assemble to generate a long, zipper-like structure that holds homologous chromosomes in close proximity and promotes the formation of genetic crossovers and accurate meiotic chromosome segregation. In recent years, numerous mutations in human SC genes have been associated with different types of male and female infertility. Here, we integrate structural information on the human SC with mouse and human genetics to describe the molecular mechanisms by which SC mutations can result in human infertility. We outline certain themes in which different SC proteins are susceptible to different types of disease mutation and how genetic variants with seemingly minor effects on SC proteins may act as dominant-negative mutations in which the heterozygous state is pathogenic.
Topics: Male; Female; Humans; Mice; Animals; Synaptonemal Complex; Chromosome Pairing; Meiosis; Infertility; Mutation; Mammals
PubMed: 37159901
DOI: 10.1146/annurev-genom-110122-090239 -
Biology of Reproduction Jun 2020
Topics: Animals; Cell Cycle Checkpoints; Cell Cycle Proteins; Humans; Male; Meiosis; Meiotic Prophase I; Metaphase; SKP Cullin F-Box Protein Ligases; Spermatozoa; Ubiquitin
PubMed: 32338765
DOI: 10.1093/biolre/ioaa063