A single light-responsive sizer can control multiple-fission cycles in Chlamydomonas

Abstract

Proliferating cells need to coordinate cell division and growth to maintain size homeostasis. Any systematic deviation from a balance between growth and division results in progressive changes of cell size over subsequent generations. While most eukaryotic cells execute binary division after a mass doubling, the photosynthetic green alga Chlamydomonas can grow more than eight-fold during daytime before undergoing rapid cycles of DNA replication, mitosis and cell division at night, which produce up to 16 daughter cells. Here, we propose a mechanistic model for multiple fission and size control in Chlamydomonas. The model comprises a light-sensitive and size-dependent biochemical toggle switch that acts as a sizer and guards transitions into and exit from a phase of cell-division cycle oscillations. We show that this simple sizer-oscillator arrangement reproduces the experimentally observed features of multiple-fission cycles and the response of Chlamydomonas cells to different light-dark regimes. Our model also makes testable predictions about the dynamical properties of the biochemical network that controls these features and about the networks makeup. Collectively, these results provide a new perspective on the concept of a commitment point during the growth of Chlamydomonas cells and hint at an intriguing continuity of cell-size control in different eukaryotic lineages.\n\nGraphical abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=182 SRC=\"FIGDIR/small/648436v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (35K):\norg.highwire.dtl.DTLVardef@48f9corg.highwire.dtl.DTLVardef@170625eorg.highwire.dtl.DTLVardef@14a20a0org.highwire.dtl.DTLVardef@1a3ff9a_HPS_FORMAT_FIGEXP M_FIG C_FIG O_LIG1-sizer and S/M-oscillator can give rise to multiple-fission cycles in Chlamydomonas\nC_LIO_LILight-responsive bistable switch may guard transition between G1 and S/M-cycles\nC_LIO_LIIllumination increases S/M-entry threshold, causing multiple-fission cycles\nC_LIO_LIDark shift lowers S/M-entry threshold, allowing small cells to commit to fewer divisions\nC_LI