Experimental evolution of cellular miniaturization reveals a mechanism for cell size evolution

Area of Science:

• Cell Biology
• Evolutionary Biology
• Genetics

Background:

• Cell volume is crucial for physiology, maintained by cell size homeostasis.
• Significant cell size deviations can be detrimental, yet evolutionary divergence is vast.
• The mechanisms enabling cell size diversity without physiological compromise are unclear.

Purpose of the Study:

• To investigate how cell size homeostasis evolves to support diverse cell sizes.
• To understand the genetic basis of cellular miniaturization in *Saccharomyces cerevisiae*.
• To explore the evolutionary plasticity of cell size regulation.

Main Methods:

• Experimental evolution selecting for smaller *Saccharomyces cerevisiae* cells over 1,500 generations.
• Whole-genome sequencing of evolved populations.
• Genetic manipulation of G1 cyclin CLN3 and Greatwall kinase RIM15 signaling pathways.

Main Results:

• Achieved a six-fold reduction in cell volume while maintaining robust and evolutionary stable size homeostasis.
• Evolved cells retained competitive fitness, demonstrating that miniaturization does not impair physiology.
• Identified CLN3 and RIM15 signaling cascades as key regulators, with adaptive mutations driving miniaturization and loss-of-function mutations causing enlargement.

Conclusions:

• Cell size homeostasis exhibits significant evolutionary plasticity.
• The CLN3 and RIM15 pathways provide a mechanism for eukaryotic cell size evolution.
• Dramatic cell size changes can be achieved without compromising cellular physiology.