MAINTENANCE OF PRE-MESSENGER-RNA SECONDARY STRUCTURE BY EPISTATIC SELECTION
MAINTENANCE OF PRE-MESSENGER-RNA SECONDARY STRUCTURE BY EPISTATIC SELECTION
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DOI：
10.1073/pnas.92.20.9047
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发表时间：
1995-09-26
影响因子：
11.1
通讯作者：
STEPHAN, W
中科院分区：
文献类型：
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作者：
KIRBY, DA;MUSE, SV;STEPHAN, W
自然群体中多态性之间的连锁不平衡可能是由各种进化力量引起的，包括由于生殖过程中配子取样引起的随机遗传漂变、细分群体中亚群体之间的限制性迁移或上位选择。我们提出的证据表明，在乙醇脱氢酶基因座（Adh）的内含子中观察到的大多数显着连锁不平衡，果蝇的基因组结构是由于上位性选择维持了前体mRNA的二级结构。基于遗传学比较分析和似然方法，我们提出了Adh前体mRNA的二级结构模型的成人内含子和内含子2的连锁不平衡的聚类已被观察到的区域，此外，我们应用似然比检验的遗传学预测的二级结构在内含子1。与其他两种结构相比，与内含子1更为保守的茎环结构相关的多态性频率较低，并且未观察到连锁不平衡。这些发现与补偿适合性相互作用模型定性一致，该模型假设破坏二级结构元件配对的突变如果使功能重要的结构不稳定，则是个体有害的;然而，第二个“补偿性”突变可能会重新稳定结构并恢复健康。
Linkage disequilibrium between polymorphisms in a natural population may result from various evolutionary forces, including random genetic drift due to sampling of gametes during reproduction, restricted migration between subpopulations in a subdivided population, or epistatic selection, In this report, we present evidence that the majority of significant linkage disequilibria observed in introns of the alcohol dehydrogenase locus (Adh) of Drosophila pseudoobscura are due to epistatic selection maintaining secondary structure of precursor mRNA (pre-mRNA). Based on phylogenetic-comparative analysis and a likelihood approach, we propose secondary structure models of Adh pre mRNA for the regions of the adult intron and intron 2 where clustering of linkage disequilibria has been observed, Furthermore, we applied the likelihood ratio test to the phylogenetically predicted secondary structure in intron 1. In contrast to the other two structures, polymorphisms associated with the more conserved stem-loop structure of intron 1 are in low frequency, and linkage disequilibria have not been observed, These findings are qualitatively consistent with a model of compensatory fitness interactions, This model assumes that mutations disrupting pairing in a secondary structural element are individually deleterious if they destabilize a functionally important structure; a second ''compensatory'' mutation, however, may restabilize the structure and restore fitness.