http://precedings.nature.com/users/f6287eb212739d8cdd3e77b2445ab83a/ Documents posted by Casey Bergman 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/ http://precedings.nature.com/documents/1988/version/1 The natural genetics of an organism is determined by the distribution of sequences of its genome. Here we present one- to four-fold, with some deeper, coverage of the genome sequences of over seventy isolates of the domesticated baker’s yeast, Saccharomyces cerevisiae, and its closest relative, the wild S. paradoxus, which has never been associated with human activity. These were collected from numerous geographic locations and sources (including wild, clinical, baking, wine, laboratory and food spoilage). These sequences provide an unprecedented view of the population structure, natural (and artificial) selection and genome evolution in these species. Variation in gene content, SNPs, indels, copy numbers and transposable elements provide insights into the evolution of different lineages. Phenotypic variation broadly correlates with global genome-wide phylogenetic relationships however there is no correlation with source. S. paradoxus populations are well delineated along geographic boundaries while the variation among worldwide S. cerevisiae isolates show less differentiation and is comparable to a single S. paradoxus population. Rather than one or two domestication events leading to the extant baker’s yeasts, the population structure of S. cerevisiae shows a few well defined geographically isolated lineages and many different mosaics of these lineages, supporting the notion that human influence provided the opportunity for outbreeding and production of new combinations of pre-existing variation. http://precedings.nature.com/documents/1988/version/1 Fri, 20 Jun 2008 15:24:32 UTC Population genomics of domestic and wild yeasts hdl:10101/npre.2008.1988.1 2008-06-20 Edward Louis Nature Precedings 2008-06-20T15:24:32Z Manuscript Ecology Genetics & Genomics Bioinformatics Evolutionary Biology http://creativecommons.org/licenses/by/3.0/