Conserved rules govern genetic interaction degree across species

Area of Science:

• Systems biology
• Genetics
• Computational biology

Background:

• Genome-wide synthetic genetic interactions mapped in Saccharomyces cerevisiae offer insights into eukaryotic life.
• Comprehensive genetic interaction networks are lacking for many species.
• Modeling conserved aspects of genetic networks facilitates interspecies knowledge transfer.

Purpose of the Study:

• To model conserved aspects of genetic interaction networks.
• To enable the transfer of genetic interaction knowledge between species.
• To predict genetic interaction degree using gene properties.

Main Methods:

• Developed predictive models using physiological and evolutionary gene properties.
• Trained models on Saccharomyces cerevisiae gene features and interaction degree.
• Validated models by predicting genetic interaction degree in Schizosaccharomyces pombe.

Main Results:

• Models accurately predicted genetic interaction degree in both S. cerevisiae and S. pombe.
• High single mutant fitness defect, protein disorder, pleiotropy, protein-protein interaction network degree, and low expression variation were predictive.
• Functional rewiring of biological processes was identified between the two yeast species.
• Predicted differences were supported by co-expression relationships.

Conclusions:

• Common relationships exist between gene properties and genetic interaction network topology in evolutionarily distant species.
• The S. cerevisiae genetic interaction network can serve as an orthology-independent reference.
• This approach aids in studying genetic interactions in more complex organisms.