Forsdyke D R
Department of Biochemistry, Queen's University, Kingston, Ontario, Canada.
J Theor Biol. 1994 Mar 7;167(1):7-12. doi: 10.1006/jtbi.1994.1045.
Muller's paradox is that X chromosome dosage compensation seems to have evolved in spite of there being only "exceedingly minute differences" between compensated and uncompensated phenotypes. The paradox can be resolved by considering, not the specific functions of individual proteins, but the collective functions of proteins per se. One such function could be the collective pressure exerted by proteins in the crowded cytosol to drive individual protein species from simple solution (aggregation) when their concentrations exceed specific thresholds. It is proposed that over evolutionary time, individual genes, both on X chromosomes and autosomes, would have fine-tuned factors such as transcription rates and protein stabilities to this collective pressure. However, without X chromosome dosage compensation the total concentration of cytosolic proteins, and hence the collective pressure, would have fluctuated between male and female generations. Fine-tuning, a process of vital importance for intracellular self/not-self discrimination, would have been severely compromised.
穆勒悖论是指,尽管在已补偿和未补偿的表型之间仅存在“极其微小的差异”,但X染色体剂量补偿似乎仍已进化。通过考虑蛋白质本身的集体功能而非单个蛋白质的特定功能,这一悖论可以得到解决。其中一种功能可能是,当蛋白质浓度超过特定阈值时,拥挤细胞质中的蛋白质所施加的集体压力会促使单个蛋白质种类从简单溶液中析出(聚集)。有人提出,在进化过程中,X染色体和常染色体上的单个基因会针对这种集体压力对诸如转录速率和蛋白质稳定性等因素进行微调。然而,如果没有X染色体剂量补偿,细胞质蛋白质的总浓度以及由此产生的集体压力,将会在雄性和雌性世代之间波动。而对于细胞内自我/非自我识别至关重要的微调过程,将会受到严重影响。