http://precedings.nature.com/users/0e3640d5d6cfd6f0e720501636d90c18/ Documents posted by Michael Barton Nature Publishing Group en Nature Precedings http://precedings.nature.com/images/header_logo.gif http://precedings.nature.com http://precedings.nature.com/documents/1841/version/2 Background: Every protein has a variable atomic and energetic cost to the cell based on the synthesis of its constituent amino acids. Quantifying the cost of amino acid synthesis is challenging, however natural selection is expected to favour the use of proteins whose constituents are cheaper to produce in terms of energetic and atomic cost.Results: We develop a systems biology approach to estimate the cost of amino acid synthesis based on genome-scale metabolic models, and directly investigate the effects of the cost of amino acid synthesis on transcriptomic, proteomic and metabolomic data in Saccharomyces cerevisiae. We used our two new and six previously reported measures of amino acid cost in conjunction with codon usage bias, tRNA gene number and atomic composition to identify the factors that predict transcript, protein and free amino acid levels in the yeast cell. While most previously reported cost measures are highly correlated, we find that our systems approach to formulating the cost of amino acid synthesis produces a novel measure of cost, which explains similar levels of variation in gene expression. Regardless of the measure used, the cost of amino acid synthesis is weakly associated with transcript and protein levels, independent of codon usage bias. In contrast, energetic costs explain a large proportion of variation in levels of free amino acids.Conclusions: In the economy of the yeast cell, the cost of amino acid synthesis correlates with transcript and protein levels to a lesser degree than translational optimisation, whereas atomic and energetic cost plays a much larger role in explaining levels in free amino acids. However, as there appears to be no single currency to compute the cost of amino acid synthesis, a systems approach is necessary to uncover the full effects of amino acid biosynthetic cost in complex biological systems that vary with cellular and environmental conditions. http://precedings.nature.com/documents/1841/version/2 Tue, 22 Jul 2008 08:38:32 UTC Systems biology of energetic and atomic costs in the yeast transcriptome, proteome, and metabolome hdl:10101/npre.2008.1841.2 2008-07-22 Michael D. Barton Nature Precedings 2008-07-22T08:38:32Z Manuscript Genetics & Genomics Molecular Cell Biology Bioinformatics http://creativecommons.org/licenses/by/3.0/