Epigenetic epistatic interactions constrain the evolution of gene expression

Area of Science:

• Genetics
• Evolutionary Biology
• Systems Biology

Background:

• Epistasis, where gene interactions modify effects, can occur through mutation or gene expression variation.
• Epigenetic interactions, arising from gene expression variation in isogenic individuals, may constrain evolutionary processes.

Purpose of the Study:

• To investigate whether epigenetic epistatic interactions impose constraints on the evolution of gene expression.
• To explore the relationship between gene expression stability and the number of epistatic interaction partners.

Main Methods:

• Analysis of gene expression variation in yeast across different conditions and in response to mutations.
• Examination of yeast promoter architectures, gene duplicate retention, and cross-species expression divergence.
• Comparative analysis of gene expression between humans and chimpanzees.

Main Results:

• Genes with numerous epistatic partners exhibit low expression variation in isogenic individuals and across conditions.
• Gene expression remains stable under mutation accumulation and diverges slowly between strains and species.
• Evidence suggests selective pressure to minimize harmful epigenetic epistatic interactions.

Conclusions:

• Tight regulation of epistatic interaction network hubs contributes to maintaining a robust, 'canalized' phenotype.
• Epigenetic epistatic interactions may significantly contribute to fitness defects upon single gene deletion.
• These findings highlight the evolutionary significance of regulating gene expression networks.