Dosage-dependent gene regulation in multicellular eukaryotes: Implicationsfor dosage compensation, aneuploid syndromes, and quantitative traits

Evidence from a variety of data suggests that regulatory mechanisms in mult icellular eukaryotes have evolved in such a manner that the stoichiometric relationship of the components of regulatory complexes affects target gene expression. This type of mechanism sets the level of gene expression and, a s a consequence, the phenotypic characteristics. Because many types of regu latory processes exhibit dosage-dependent behavior, they would impact quant itative traits and contribute to their multigenic control in a semidominant fashion. Many dosage-dependent effects would also account for the extensiv e modulation of gene expression throughout the genome that occurs when chro mosomes are added to or subtracted from the karyotype (aneuploidy). Moreove r, because the majority of dosage-dependent regulators act negatively, this property can account for the up-regulation of genes in monosomics and hemi zygous sex chromosomes to achieve dosage compensation. (C) 2001 Academic Pr ess.