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Repurposing of synaptonemal complex proteins for kinetochores in Kinetoplastida.

ABSTRACT: Chromosome segregation in eukaryotes is driven by the kinetochore, a macromolecular complex that connects centromeric DNA to microtubules of the spindle apparatus. Kinetochores in well-studied model eukaryotes consist of a core set of proteins that are broadly conserved among distant eukaryotic phyla. By contrast, unicellular flagellates of the class Kinetoplastida have a unique set of 36 kinetochore components. The evolutionary origin and history of these kinetochores remain unknown. Here, we report evidence of homology between axial element components of the synaptonemal complex and three kinetoplastid kinetochore proteins KKT16-18. The synaptonemal complex is a zipper-like structure that assembles between homologous chromosomes during meiosis to promote recombination. By using sensitive homology detection protocols, we identify divergent orthologues of KKT16-18 in most eukaryotic supergroups, including experimentally established chromosomal axis components, such as Red1 and Rec10 in budding and fission yeast, ASY3-4 in plants and SYCP2-3 in vertebrates. Furthermore, we found 12 recurrent duplications within this ancient eukaryotic SYCP^2-3 gene family, providing opportunities for new functional complexes to arise, including KKT16-18 in the kinetoplastid parasite Trypanosoma brucei. We propose the kinetoplastid kinetochore system evolved by repurposing meiotic components of the chromosome synapsis and homologous recombination machinery that were already present in early eukaryotes.

SUBMITTER: Tromer EC

PROVIDER: S-EPMC8131943 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Conservation and variability of synaptonemal complex proteins in phylogenesis of eukaryotes.

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Project description:The synaptonemal complex (SC) is a proteinaceous, meiosis-specific structure that is highly conserved in evolution. During meiosis, the SC mediates synapsis of homologous chromosomes. It is essential for proper recombination and segregation of homologous chromosomes, and therefore for genome haploidization. Mutations in human SC genes can cause infertility. In order to gain a better understanding of the process of SC assembly in a model system that would be relevant for humans, we are investigating meiosis in mice. Here, we report on a newly identified component of the murine SC, which we named SYCE3. SYCE3 is strongly conserved among mammals and localizes to the central element (CE) of the SC. By generating a Syce3 knockout mouse, we found that SYCE3 is required for fertility in both sexes. Loss of SYCE3 blocks synapsis initiation and results in meiotic arrest. In the absence of SYCE3, initiation of meiotic recombination appears to be normal, but its progression is severely impaired resulting in complete absence of MLH1 foci, which are presumed markers of crossovers in wild-type meiocytes. In the process of SC assembly, SYCE3 is required downstream of transverse filament protein SYCP1, but upstream of the other previously described CE-specific proteins. We conclude that SYCE3 enables chromosome loading of the other CE-specific proteins, which in turn would promote synapsis between homologous chromosomes.

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Project description:The synaptonemal complex (SC) is a proteinaceous scaffold required for synapsis and recombination between homologous chromosomes during meiosis. Although the SC has been linked to differences in genome-wide crossover rates, the genetic basis of standing variation in SC structure remains unknown. To investigate the possibility that recombination evolves through changes to the SC, we characterized the genetic architecture of SC divergence on two evolutionary timescales. Applying a novel digital image analysis technique to spermatocyte spreads, we measured total SC length in 9,532 spermatocytes from recombinant offspring of wild-derived mouse strains with differences in this fundamental meiotic trait. Using this large dataset, we identified the first known genomic regions involved in the evolution of SC length. Distinct loci affect total SC length divergence between and within subspecies, with the X chromosome contributing to both. Joint genetic analysis of MLH1 foci-immunofluorescent markers of crossovers-from the same spermatocytes revealed that two of the identified loci also confer differences in the genome-wide recombination rate. Causal mediation analysis suggested that one pleiotropic locus acts early in meiosis to designate crossovers prior to SC assembly, whereas a second locus primarily shapes crossover number through its effect on SC length. One genomic interval shapes the relationship between SC length and recombination rate, likely modulating the strength of crossover interference. Our findings pinpoint SC formation as a key step in the evolution of recombination and demonstrate the power of genetic mapping on standing variation in the context of the recombination pathway.

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