The Comparative Approach To Functional Analysis Of Gene Essentiality Across17Species

A clear perception of gene essentiality in pathogens is vital for identifying drug targetsto combat emergence of new pathogens and antibiotic-resistant bacteria,for syntheticbiology,and for understanding the origins of life. Comparative analysis within the functionalcontext is suggested to be a powerful approach to enhancing the predictive power. Using thisapproach we investigated the distribution of essential and dispensable functional roles of17species from6phyla in a set of22functional catagories. The result shows that translationsystem was the categories with the highest content of essential genes for all species. Otherfunctional categories enriched for essential genes were Glycan Metabolism, Cofactors andVitamins Metabolism, Nucleotide Metabolism, Replication and Repair, Protein FoldingSorting and Degradation. There were significant variations in the relative content of essentialand dispensable functions between the organisms, showing the difference in their life stylesand subsystem topologies. For example, the number of essential genes in Fungi is15timesthat in bacteria(P-value=8.28E-88). Next, in order to explore the reasons of the discrepancy ofessential genes among different species, we first cluster species based on all essential geneswith function annotation. Then we cluster species based on essential genes with function ofmaintenance of cell envelope, energy production, cofactor biosynthesis and membranetransport. The cluster analysis shows that the differences of essential genes betweenorganisms were depend on not only evolution distance but also on varied function andlifestyle. Last, we analyzed essential genes by network functions using systems biology. Allessential genes and their related functions were linked together in pathways and studied as awhole. This picture was simplified dramatically when it became apparent that all of thesepathways could be linked to three basic biological functions: maintenance of the cellenvelope, energy production and biosynthesis of cofactors.have established essential pathwaymodel for6phyla, in which the essential genes are linked by crucial chemical compounds,reflecting essential pathways for specific life form. The model could be used to predictessential genes for more bacteria for which an annotated genome sequence is available.