Nonlinear Effects in Macromolecular Assembly and Dosage Sensitivity

✍ Scribed by REINER A. VEITIA

• Book ID: 102613932
• Publisher: Elsevier Science
• Year: 2003
• Tongue: English
• Weight: 281 KB
• Volume: 220
• Category: Article
• ISSN: 0022-5193
• DOI: 10.1006/jtbi.2003.3105

✦ Synopsis

Haploinsufficiency refers to dominant abnormal phenotypes resulting from the absence of substantial activity from one allele at a normally diploid locus. Haploinsufficiency may also result from an altered stoichiometry in a macromolecular complex. Higher-than-diploid levels of a gene product can also induce abnormalities that may even resemble the haploinsufficient phenotype. Here, I explore possible non-linearities in the assembly of multimeric molecules from the perspective of dose effects. I propose that for any oligomer assembly reaction, there may be a set of conditions (initial subunit concentrations and equilibrium constants) such that changing the input concentration of one component (0.5 x or 1.5x) will lead to a minimum and non-proportional change of the final oligomer concentration. This buffer effect is a general property of multimeric systems in equilibrium and can be, in principle, exploited by selection to diminish dosage sensitivity. Other effects involving cooperativity or sequential assembly may also play a role in palliating the effect of changes in input amounts of monomers.