Gene coevolution - which refers to gene pairs whose evolutionary rates covary across speciation events - is often observed among functionally related genes. We present a comprehensive gene coevolution network inferred from the examination of nearly three million gene pairs from 332 budding yeast species spanning ~400 million years of eukaryotic evolution. Modules within the network provide insight into cellular and genomic structure and function, such as genetic pleiotropy, genes functioning in distinct cellular compartments, vesicle transport, and DNA replication. Examination of the phenotypic impact of network perturbation across 14 environmental conditions using deletion mutant data from the baker's yeast Saccharomyces cerevisiae suggests that fitness in diverse environments is impacted by gene neighborhood and gene connectivity. By mapping the network onto the chromosomes of S. cerevisiae and the opportunistic human pathogen Candida albicans, which diverged ~235 million years ago, we discovered that coevolving gene pairs are not clustered in either species; rather, they are most often located on different chromosomes or far apart on the same chromosome. The budding yeast gene coevolution network captures the hierarchy of eukaryotic cellular structure and function, provides a roadmap for genotype-to-phenotype discovery, and portrays the genome as an extensively linked ensemble of genes.
Structure and function of cytochromes P450:a comparative analysis of three crystal structures
