Network hubs buffer environmental variation in Saccharomyces cerevisiae.

Area of Science:

• Evolutionary biology
• Genetics
• Molecular biology

Background:

• Phenotypic robustness is crucial for development and regulation, maintained by phenotypic capacitors.
• Failure of these capacitors, like Hsp90, can expose cryptic genetic variation, potentially driving evolutionary change.
• Previous simulations predicted numerous gene products acting as phenotypic capacitors.

Purpose of the Study:

• To experimentally identify gene products that act as phenotypic capacitors in Saccharomyces cerevisiae.
• To investigate the characteristics and genetic architecture of these buffering gene products.

Main Methods:

• High-throughput morphological phenotyping of individual yeast cells from single-gene deletion strains.
• Analysis of over 300 gene products that, upon deletion, increased morphological variation.

Main Results:

• Identified over 300 gene products that buffer environmental variation, acting as phenotypic capacitors.
• Capacitors are enriched in functions related to chromosome organization, DNA integrity, RNA processing, cell cycle, and stress response.
• Capacitors with gene duplicates are highly connected and show expression divergence; those without duplicates are in interconnected clusters affecting variability.

Conclusions:

• Buffering and release of phenotypic variation is a widespread phenomenon mediated by incomplete functional redundancy.
• These findings highlight the role of phenotypic capacitors in maintaining robustness and facilitating evolutionary adaptation.
• The study reveals a complex genetic architecture underlying phenotypic buffering across multiple levels.