Bagheri-Chaichian Homayoun, Hermisson Joachim, Vaisnys Juozas R, Wagner Günter P
Santa Fe Institute, 1399 Hyde Park Road, Santa Fe, NM 87501, USA.
Math Biosci. 2003 Jul;184(1):27-51. doi: 10.1016/s0025-5564(03)00057-9.
It is an open question whether phenomena such as phenotypic robustness to mutation evolve as adaptations or are simply an inherent property of genetic systems. As a case study, we examine this question with regard to dominance in metabolic physiology. Traditionally the conclusion that has been derived from Metabolic Control Analysis has been that dominance is an inevitable property of multi-enzyme systems and hence does not require an evolutionary explanation. This view is based on a mathematical result commonly referred to as the flux summation theorem. However it is shown here that for mutations involving finite changes (of any magnitude) in enzyme concentration, the flux summation theorem can only hold in a very restricted set of conditions. Using both analytical and simulation results we show that for finite changes, the summation theorem is only valid in cases where the relationship between genotype and phenotype is linear and devoid of non-linearities in the form of epistasis. Such an absence of epistasis is unlikely in metabolic systems. As an example, we show that epistasis can arise in scenarios where we assume generic non-linearities such as those caused by enzyme saturation. In such cases dominance levels can be modified by mutations that affect saturation levels. The implication is that dominance is not a necessary property of metabolic systems and that it can be subject to evolutionary modification.
表型对突变的稳健性等现象是作为适应性进化而来，还是仅仅是遗传系统的固有属性，这是一个悬而未决的问题。作为一个案例研究，我们针对代谢生理学中的显性现象来研究这个问题。传统上，从代谢控制分析得出的结论是，显性是多酶系统的必然属性，因此不需要进化解释。这一观点基于一个通常被称为通量总和定理的数学结果。然而，这里表明，对于涉及酶浓度有限变化（任何幅度）的突变，通量总和定理仅在非常有限的一组条件下成立。利用分析和模拟结果，我们表明，对于有限变化，总和定理仅在基因型与表型之间的关系是线性且不存在上位性形式的非线性的情况下才有效。在代谢系统中不太可能不存在上位性。例如，我们表明，在我们假设存在一般非线性（如由酶饱和引起的非线性）的情况下会出现上位性。在这种情况下，显性水平可以被影响饱和水平的突变所改变。这意味着显性不是代谢系统的必要属性，并且它可以受到进化修饰。
