PDF(Pubmed)
Abstract：
RNA and protein expressed from the same gene can have diverse isoforms due to various post-transcriptional and post-translational modifications. For the vast majority of alternative isoforms, It is unknown whether they are adaptive or simply biological noise. As we cannot experimentally probe the function of each isoform, we can ask whether the distribution of isoforms across genes and across species is consistent with expectations from different evolutionary processes. However, there is currently no theoretical framework that can generate such predictions. To address this, we developed a mathematical model where isoform abundances are determined collectively by cis-acting loci, trans-acting factors, gene expression levels, and isoform decay rates to predict isoform abundance distributions across species and genes in the face of mutation, genetic drift, and selection. We found that factors beyond selection, such as effective population size and the number of cis-acting loci, significantly influence evolutionary outcomes. Notably, suboptimal phenotypes are more likely to evolve when the population is small and/or when the number of cis-loci is large. We also explored scenarios where modification processes have both beneficial and detrimental effects, revealing a non-monotonic relationship between effective population size and optimization, demonstrating how opposing selection pressures on cis- and trans-acting loci can constrain the optimization of gene product diversity. As a demonstration of the power of our theory, we compared the expected distribution of A-to-I RNA editing levels in coleoids and found this to be largely consistent with non-adaptive explanations.
摘要：
由于各种转录后和翻译后修饰,从相同基因表达的RNA和蛋白质可以具有不同的同种型。对于绝大多数替代亚型，尚不清楚它们是自适应的还是简单的生物噪声。由于我们无法通过实验探究每种同工型的功能，我们可以问，同工型在基因和物种之间的分布是否与不同进化过程的预期一致。然而,目前没有理论框架可以产生这样的预测。为了解决这个问题，我们开发了一个数学模型，其中同工型丰度由顺式作用基因座共同确定，反式作用因素，基因表达水平，和同工型衰变率来预测面对突变时物种和基因的同工型丰度分布，遗传漂移，和选择。我们发现除了选择之外的因素，如有效种群大小和顺式作用基因座的数量，显著影响进化结果。值得注意的是,当种群较小和/或顺式基因座数量较大时，次优表型更有可能进化。我们还探讨了修改过程既有有益影响又有有害影响的情况，揭示了有效种群规模与优化之间的非单调关系，证明了对顺式和反式作用基因座的相反选择压力如何限制基因产物多样性的优化。为了证明我们理论的力量，我们比较了胚状体中A-IRNA编辑水平的预期分布,发现这与非适应性解释基本一致.
