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.

Kinetoplastid kinetochore proteins KKT2 and KKT3 have unique centromere localization domains

“…KKT4 is the only known microtubule-binding kinetochore protein in T. brucei ( Llauró et al, 2018 ). Direct protein–protein interactions among kinetoplastid kinetochore proteins remain unknown except for KKT16/17/18 that form the KKT16 complex ( Tromer et al, 2021 ), KKT8/9/11/12 that form the KKT8 complex, and KKT7 that binds KKT10 and KKT19 ( Ishii and Akiyoshi, 2020 ). Known substrates of the KKT10/19 kinases include KKT4 and KKT7 ( Ishii and Akiyoshi, 2020 ), while substrates of KKT2/3 remain unknown.…”

“…They instead have unique kinetochore proteins, such as KKT1–25 ( Akiyoshi and Gull, 2014 ; Nerusheva and Akiyoshi, 2016 ; Nerusheva et al, 2019 ) and KKIP1–12 ( D’Archivio and Wickstead, 2017 ; Brusini et al, 2021 ) in T. brucei . Some of these kinetochore proteins have similarities to meiotic synaptonemal complex or homologous recombination components, suggesting that kinetoplastids might have evolved their unique kinetochore system by repurposing components of the chromosome synapsis and homologous recombination machinery ( Tromer et al, 2021 ). It remains unknown which kinetochore proteins form the base of kinetoplastid kinetochores that recruits other proteins.…”

Plasticity in centromere organization and kinetochore composition: Lessons from diversity

“…This possibility is in line with the distinct geometry of their sister kinetochores observed by electron microscopy: unlike non-kinetoplastid species that have ∼1 μm distance between sister kinetochores in metaphase (the space is called the inner centromere) [ 48 ], there is no such space in kinetoplastids [ 49 , 50 ]. Interestingly, KKT16–18 are divergent homologs of SYCP2 and SYCP3, which are axial element components of the synaptonemal complex (SC) [ 51 ]. The SC is a meiosis-specific zipper-like structure that assembles between homologous chromosomes to promote recombination.…”

“…The SC is a meiosis-specific zipper-like structure that assembles between homologous chromosomes to promote recombination. It has been proposed that the ancestor of kinetoplastids repurposed the meiotic machinery to assemble unique kinetochores [ 51 ]. It remains to be determined to what extent kinetoplastid kinetochores share functional and structural similarities with synaptonemal complexes.…”

Experimental Hybridization in Leishmania: Tools for the Study of Genetic Exchange

“…Interestingly, the highest similarities were found between SYCP2-SYCP3 and KKT16-KKT18 proteins, which form the kinetoplastid kinetochore responsible for the mitotic segregation of sister chromatids. It has been proposed that the ancestral kinetoplastid kinetochore was repurposed from meiotic SC structural components [ 51 ].…”