Genetic variability of proteome expression and metabolic control

Quantitative proteomics, the technology for high-throughput measurement of protein concentrations from 2-D electrophoresis, often reveals high levels of genetic variability of proteome expression in the species studied. A maj ority of proteins, including enzymes, display quantitative variation, the e xtent of which may exceed an order of magnitude. As can be attested in vari ous studies, and most notably in maize, the concentration of individual pro teins appears to be a polygenic trait, whose loci may be distributed throug hout the genome, with possibly large effects and frequent epistatic interac tions. In order to analyse the genetic consequences of these variations, we used the metabolic control theory, developing equations that explicitly in corporate the enzyme concentration as the relevant variable. The metabolic fluxes were modelled as quantitative traits affected by genes modulating en zyme quantities. We showed that, in addition to the classical positive domi nance of a large concentration over a small concentration, heterosis for th e flux is observed in cases of complementary dominance at different loci. C onstraints on the total quantity of enzymes may produce overdominance, rein forcing heterosis. Beyond these genetic aspects, biochemical modelling appe ars as an important component of genomic and post-genomic approaches, allow ing the integration of data generated in those high-throughput programs. (C ) 2001 Editions scientifiques et medicales Elsevier SAS.