Transcriptomic and proteomic effects of gene deletion are not evolutionarily conserved

Area of Science:

• Molecular Biology
• Genetics
• Systems Biology

Background:

• Gene function is typically inferred from phenotypic changes observed after gene deletion.
• However, deletion effects can be byproducts, not reflecting the gene's selected-effect function.
• Understanding the reliability of gene deletion effects is crucial for accurate gene function assessment.

Purpose of the Study:

• To evaluate how well phenotypic effects of gene deletion inform selected-effect gene function.
• To compare transcriptomic and proteomic effects of gene deletions between budding yeast (Saccharomyces cerevisiae) and fission yeast (Schizosaccharomyces pombe).

Main Methods:

• Systematic gene deletions were performed in Saccharomyces cerevisiae and Schizosaccharomyces pombe.
• Transcriptomic and proteomic effects of these deletions were analyzed and compared.
• Effects were also analyzed across different S. cerevisiae strains and between laboratories.

Main Results:

• Despite conserved orthologous genes, deletions showed no more shared transcriptomic or proteomic effects between species than non-orthologous genes.
• Transcriptomic effects of deleting the same gene strongly overlapped within S. cerevisiae studies, ruling out rapid evolution or measurement error.
• Deletion effects showed high sensitivity to genetic background in S. cerevisiae, explaining lack of evolutionary conservation.

Conclusions:

• Most transcriptomic and proteomic effects of gene deletion do not accurately inform selected-effect gene function.
• Gene deletion effects are highly sensitive to genetic background, limiting their evolutionary conservation.
• Findings have significant implications for assessing gene function, pleiotropy, and biological complexity.