Fine tuning of intracellular protein concentrations, a collective protein function involved in aneuploid lethality, sex-determination and speciation?

Abstract

The assertion that sex chromosome dosage compensation arose because aneuploidy for an entire chromosome is lethal, begs the question of why aneuploidy is lethal. It has been proposed that aneuploid lethality results from impairment of a collectiveprotein function (Forsdyke, 1994, J. theor. Biol. 167,7–12). Cytosolic proteins, by virtue of their concentrations, exert a pressure tending to drive members of individual protein species into self-aggregates. Other evolutionary time, each gene has fine-tuned the concentration of its product to a maximum consistent with avoiding self-aggregation in the crowded cytosol. Because of this aggregation pressure and the imprecision of their own fine-tuning, the proteins of members of other species, the corresponding genes of which may have been transported to a cell as viruses (or gametes), are specifically aggregated. The death of the cell and its enclosed virus results. Aneuploidy impairs this process, with lethal consequences for the organism. The hypothesis leads to explanations for a variety of phenomena. On the assumption that the concentration of autosomal products determines cell volume, the observed dependence of sex-determination on the ratio of X chromosomes to autosomes is shown merely to be a dependence on the concentration of the products of one X chromosome. The inviability of the heterogametic sex among the offspring of an interspecies cross (Haldane’s rule), follows from the species-specific fine-tuning of the concentrations of X chromosome-encoded products relative to the concentration of autosomally-encoded products. Species may initially have evolved as a barrier behind which fine-tuning could occur to protect cells against intracellular pathogens.