Model scenarios for evolution of the eukaryotic cell cycle

Area of Science:

• Cell Biology
• Systems Biology
• Evolutionary Biology

Background:

• Eukaryotic cell cycle progression is regulated by complex networks involving cyclin-dependent kinases (CDKs), regulatory kinases/phosphatases, and stoichiometric inhibitors.
• The regulation of cell division in early eukaryotic ancestors is presumed to be simpler than in modern cells.

Purpose of the Study:

• To mathematically model Nasmyth's proposed mechanism for a primordial eukaryotic cell cycle control.
• To investigate the core regulatory principles underlying eukaryotic cell division.

Main Methods:

• Mathematical modeling of a proposed primordial cell cycle mechanism.
• Analysis of system dynamics, including steady states and transitions between them.

Main Results:

• The model exhibits hysteretic behavior between two alternative steady states: a G1-like state and an S/M-like state.
• Cell growth drives the G1 to S/M transition ('Start'), while DNA synthesis completion and chromosome alignment drive the S/M to G1 transition ('Finish').
• This core mechanism effectively couples cell growth with division and ensures accurate genome replication and partitioning.

Conclusions:

• The proposed simple mechanism of antagonistic interactions between cyclin-CDK and the anaphase promoting complex (APC) could represent the core of the eukaryotic cell cycle.
• This model provides a foundation for understanding the evolution of more complex cell cycle regulatory networks.
• Speculation on the evolutionary addition of stoichiometric inhibitors and CDK inhibitory phosphorylation to this primitive core mechanism.