10 December

Thesis defense Jolien van Hooff: the evolutionary origin and divergence of the eukaryotic kinetochore

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Jolien van Hooff from the groups of Geert Kops (Hubrecht Institute) and Berend Snel (University Utrecht) successfully defended her thesis on the 10th of December. During her PhD, Van Hooff investigated the evolutionary origin and divergence of the eukaryotic kinetochore, a complex structure of many proteins that ensures correct segregation of DNA during cell division.

Evolutionary tree including prokaryotes (bacteria, archaea and asgard) and eukaryotes (eukarya)

Prokaryotes and eukaryotes
Eukaryote cells, such as from plants, animals and fungi, differ fundamentally from prokaryote cells, such as bacteria. Eukaryote cells have specialized organelles that perform certain functions, while prokaryote cells do not. Eukaryote cells are also on average larger than prokaryote cells. The evolutionary origin of eukaryotes can be studied more effectively nowadays, because of advancements in molecular techniques and analysis, such as comparative genomics.

Left: the microtubule-organizing centers pull one copied chromatid via the microtubules and kinetochores to each side of the cell. Right: the kinetochore is a complex structure of many proteins.

The kinetochore
One of the characteristics that seperates the prokaryotes from the eukaryotes is the kinetochore. The kinetochore is a complex structure of many proteins that enables the correct segregation of chromosomes during cell division. It connects the chromosomes to the microtubule-organizine center on each side of the cell via the microtubules. Since the kinetochore enables the attachment of the microtubules to the sister chromatids of each chromosome, it enables the correct segregation of the sister chromatids over the daughter cells.

The evolution of the kinetochore

The evolution of the kinetochore
During her PhD, Van Hooff compared the DNA sequence encoding 70 different kinetochore proteins between 90 species of eukaryotes and prokaryotes to study the evolutionary origin and divergence of these proteins. This showed that the kinetochore is very diverse and that this is due to gene loss, gene duplications and genesis (or de novo gene origin). In addition she found that genes from the same kinetochore complex are lost together, resulting in a modular evolution of the kinetochore. This confirms the dependence of genes within a module on each other.

Van Hooff also found that the complex kinetochore likely has a mosaic origin, because the proteins of the ancestral kinetochore are homologous to proteins that have a function in other eukaryotic systems, such as ubiquitination, DNA regulation and intracellular transport. In addition, many kinetochore proteins are homologous to each other, which is the result of gene duplications after which both copies kept playing a role in the kinetochore. These dupications are called intrakinetochoreduplications.

Jolien van Hooff did her PhD in the groups of Geert Kops and Berend Snel between December 2013 and July 2018. She currently works as junior researcher at the “Rekenkamer Rotterdam”, where she conducts research into the policy of the municipality of Rotterdam.

 

Geert Kops is group leader at the Hubrecht Institute, professor of Molecular Tumor Cell Biology at the University Medical Center Utrecht and Oncode Investigator.

 

Berend Snel is professor in bioinformatics at Utrecht University and leads the Evolutionary Genomics and Integrative Bioinformatics group.