An orthologous gene coevolution network provides insight into eukaryotic cellular and genomic structure and function

Area of Science:

• Evolutionary biology
• Systems biology
• Genomics

Background:

• The evolutionary rates of functionally related genes often covary, suggesting underlying biological connections.
• Understanding these connections is crucial for deciphering genome organization and function.

Purpose of the Study:

• To construct a comprehensive gene coevolution network using a large dataset of orthologous gene pairs.
• To investigate the relationship between gene coevolution, cellular function, and organismal fitness.
• To explore the spatial organization of coevolving genes within eukaryotic genomes.

Main Methods:

• Inferred a gene coevolution network from approximately 3 million orthologous gene pairs across 332 budding yeast species.
• Analyzed network modules to understand cellular and genomic structure.
• Examined the phenotypic impact of network perturbation using deletion mutant data from *Saccharomyces cerevisiae*.
• Mapped the coevolution network onto the chromosomes of *Saccharomyces cerevisiae* and *Candida albicans*.

Main Results:

• The gene coevolution network revealed modules offering insights into cellular and genomic structure and function.
• Perturbing the network demonstrated that orthologous gene neighborhood and connectivity affect fitness in diverse environments.
• Coevolving orthologous genes are not physically clustered on chromosomes; they are often located on different chromosomes or far apart on the same chromosome.
• The network captures the hierarchy of cellular structure and function.

Conclusions:

• The gene coevolution network serves as a roadmap for genotype-to-phenotype discovery.
• The genome is portrayed as a linked ensemble of genes, not just individual units.
• Gene coevolutionary patterns provide fundamental insights into genome organization and evolutionary processes.