Chromatin Regulation and Gene Centrality Are Essential for Controlling Fitness Pleiotropy in Yeast

BACKGROUND There are a wide range of phenotypes that are due to loss-of-function or null mutations. Previously, the functions of gene products that distinguish essential from nonessential genes were characterized. However, the functions of products of non-essential genes that contribute to fitness remain minimally understood. PRINCIPAL FINDINGS Using data from Saccharomyces cerevisiae, we investigated several gene characteristics, which we are able to measure, that are significantly associated with a gene's fitness pleiotropy. Fitness pleiotropy is a measurement of the gene's importance to fitness. These characteristics include: 1) whether the gene's product functions in chromatin regulation, 2) whether the regulation of the gene is influenced by chromatin state, measured by chromatin regulation effect (CRE), 3) whether the gene's product functions as a transcription factor (TF) and the number of genes a TF regulates, 4) whether the gene contains TATA-box, and 5) whether the gene's product is central in a protein interaction network. Partial correlation analysis was used to study how these characteristics interact to influence fitness pleiotropy. We show that all five characteristics that were measured are statistically significantly associated with fitness pleiotropy. However, fitness pleiotropy is not associated with the presence of TATA-box when CRE is controlled. In particular, two characteristics: 1) whether the regulation of a gene is more likely to be influenced by chromatin state, and 2) whether the gene product is central in a protein interaction network measured by the number of protein interactions were found to play the most important roles affecting a gene's fitness pleiotropy. CONCLUSIONS These findings highlight the significance of both epigenetic gene regulation and protein interaction networks in influencing the fitness pleiotropy.