Large-scale chemical genetics screens (chemogenomics) in yeast have been widely used to find drug targets, understand the mechanism-of-action of compounds, and unravel the biochemistry of drug resistance. Chemogenomics is based on the comparison of growth of gene deletants in the presence and absence of a chemical substance. Such studies showed that more than 90% of the yeast genes are required for growth in the presence of at least one chemical. Analysis of these data, using computational approaches, has revealed non-trivial features of the natural chemical tolerance systems. As a result two non-overlapping sets of genes are seen to respectively impart robustness and evolvability in the context of natural chemical resistance. The former is composed of multidrug-resistance genes, whereas the latter comprises genes sharing chemical genetic profiles with many others. Recent publications showing the potential applications chemogenomics in studying the pharmacological basis of various drugs are discussed, as well as the expansion of chemogenomics to other organisms. Finally, integration of chemogenomics with sensitive sequence analysis and ubiquitination/phosphorylation data led to the discovery of a new conserved domain and important post-translational modification pathways involved in stress resistance.
Keywords: chemogenomics, yeast, chemical genetics, evolution, multi drug resistance, biochemistry, ubiquitin, phosphorylation
Citation: Venancio TM, Bellieny-Rabelo D and Aravind L (2012) Evolutionary and biochemical aspects of chemical stress resistance in Saccharomyces cerevisiae. Front. Gene. 3:47. doi: 10.3389/fgene.2012.00047
Received: 12 January 2012; Accepted: 15 March 2012;
Published online: 30 March 2012.
Edited by:Norman Pavelka, Agency for Science, Technology and Research (A*STAR), Singapore
Reviewed by:Roger Guimera, Institució Catalana de Recerca i Estudis Avançats–Universitat Rovira i Virgili, Spain
Copyright: © 2012 Venancio, Bellieny-Rabelo and Aravind. This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.
*Correspondence: Thiago Motta Venancio, Laboratório de Química e Função de Proteínas e Peptídeos, Centro de Biocigências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Av. Alberto Lamego 2000, Campos dos Goytacazes, Rio de Janeiro, Brazil. e-mail: firstname.lastname@example.org