Repurposing of Synaptonemal Complex Proteins for Kinetochores in Kinetoplastida

Eelco C. Tromer, Thomas A. Wemyss, Ross F. Waller, Bungo Akiyoshi

Posted on: 17 May 2021 , updated on: 18 May 2021

Preprint posted on 6 February 2021

Article now published in Open Biology at http://dx.doi.org/10.1098/rsob.210049

Trypanosome kinetochores repurpose components of the synaptonemal complex

Selected by Hiral Shah, Dey Lab

Categories: bioinformatics, cell biology, evolutionary biology

Background

Kinetochores are macromolecular protein complexes that bring about the segregation of chromosomes during cell division. Kinetochores vary across eukaryotes in protein composition and sequence1. A striking example of divergence is seen in Kinetoplastida. Kinetoplastida are a group of unicellular flagellates including parasites like Trypanosoma and Leishmania spp. within the phylum Euglenozoa. Trypanosoma has a kinetochore made up of KKT/KKIP proteins functionally analogous to the canonical kinetochore found in model organisms, but lacks any direct homologs of its components. Why and how do proteins with such apparently critical cellular functions evolve so rapidly? More specifically, how did this novel/unique kinetoplastid kinetochore emerge? Were they acquired from endosymbionts or did they evolve by repurposing other cellular machinery?

Key findings and future directions

The canonical kinetochore has a mosaic origin, with many components sharing their ancestry with proteins performing a range of functions that include vesicular transport, DNA replication and repair and transcription2. Could this also be true for the kinetoplastids? While it was not possible to identify kinetochore protein homologs, many of the KKT proteins had generic domains shared with proteins involved in homologous recombination, DNA repair and cell cycle regulators like Polo kinases. This provided a clue about what might be going on in Kinetoplastids. Interestingly, KKT17/18, two components of the three member KKT16 subcomplex, that likely emerged through gene duplication, displayed a unique domain topology of Armadillo repeats (ARM) with a Pleckstrin homology (PH) domain followed by coiled coils. This domain arrangement is only found in SYCP2, a protein of the synaptonemal complex that links chromosomes during meiotic homologous recombination suggesting a shared evolutionary history and repurposing of meiotic components for different cellular functions in mitosis.

Figure 1: Evolutionary scenario of SYCP2-3 proteins (Figure 5 from preprint, provided under CC BY 4.0 International License)

Using an iterative alignment method that merged clade-specific alignments into a super alignment, the authors identified SYCP2-3 family proteins that were normally difficult to detect or establish relationships with using only metazoan references across eukaryotes, including Giardia, microsporidia and diverse fungi, suggesting an ancient origin of these kinetoplastid kinetochores. Further, most lineages that lacked any SYCP2-3 also have not revealed any synaptonemal complex structures. Therefore, the presence of SYCP2-3 in a proteome could be a potential indicator of the presence of the synaptonemal complex in the organism.

While this gives us a glimpse into the evolutionary history of this unique kinetochore, its relationship with the other present day eukaryotic and ancient kinetochores is still unclear. Did the early kinetoplastids replace their canonical kinetochores with this new one? Or did early eukaryotes have a kinetochore different from all systems present today, that diverged along these many different paths? Well, only more such studies within the euglenozoa on close relatives like Diplonemida, and across eukaryotes more broadly, will provide a better picture of the ancestry of this unique and essential kinetochore complex.

References

van Hooff JJ, Tromer E, van Wijk LM, Snel B, Kops GJ.Evolutionary dynamics of the kinetochore network in eukaryotes as revealed by comparative genomics. EMBO Rep. 2017;18(9):1559-1571.
Eelco C Tromer, Jolien J E van Hooff, Geert J P L Kops, Berend Snel. Mosaic origin of the eukaryotic kinetochore. Proc Natl Acad Sci U S A. 116(26):12873-12882. doi: 10.1073/pnas.1821945116.