Origin and Evolution of Nuclear pre-mRNA Introns

对于内含子作为基因结构的一部分出现得早还是晚的争论，将试图提供一个更合理的解决方案。建立全面的计算机化内含子数据库。我们将通过确定不同真核生物中基因三磷酸异构酶（TPI）的内含子结构来测试这两种理论的五个关键预测，该基因在这场争议中最常被使用。我们还将使用该数据库来评估真核生物主要群体中内含子获得和丢失的时间动态，最后，我们将研究最近的内含子明显插入或滑动的案例，以便深入了解可能的机制。内含子是一种中断基因的非编码序列，在RNA水平上通过RNA剪接被移除，是许多真核蛋白基因的标志。这一点在人类和其他脊椎动物身上体现得最为明显，它们占据了基因长度的80-90%，数量接近100万个。自从16年前发现内含子（今年为此获得了诺贝尔奖）以来，一场关于内含子的进化起源和重要性的根本性争论就一直在激烈进行。为了直接解决并试图解决这一长期存在的争议，我们将开发一个全面的、计算机化的内含子数据库，并使用它来评估真核生物中内含子的分布是否最适合“内含子早”或“内含子晚”理论的竞争原则。此外，我们将测试这两种理论的五个关键预测，通过确定在各种不同的真核生物中，基因TPI的内含子结构在这场争论中最为突出。我们还将通过使用内含子数据库来评估真核生物，特别是动物、植物和真菌的主要群体中内含子获得和丢失的时间动态，从而超越这一争论。初步分析表明，这是一种高度偶发的模式，这提出了惊人的机制和选择性问题。最后，我们将特别研究最近的内含子明显插入或滑动的情况，以了解这些事件是如何发生的。* * *

Palmer MCB-9318858 Abstract An attempt to provide a more rationale resolution to the ongoing controversy of whether introns appeared early or late as a part of the structure of genes will be made. We will develop a comprehensive, computerized intron database. We will test five key predictions of both theories by determining in diverse eukaryotes the intron structure of the gene triphophate isomerase (TPI), the gene which has most often been utilized in this controversy. We will also use the database to evaluate the temporal dynamics of intron gain and loss among the major groups of erkaryotes and, finally, we will examine recent cases of the apparent insertion or sliding of introns in order to gain insight into possible mechanisms. %%% Introns - noncoding sequences that interrupt genes and which are removed at the RNA level via RNA splicing - are the hallmarks of many eukaryotic protein genes. Nowhere is this more true than in humans and other vertebrates, where they occupy 80-90% of a gene's length and number nearly a million. Ever since their discovery 16 years ago (for which a Nobel Prize was awarded this year), a fundamental controversy has raged concerning the evolutionary origin and importance of introns. In order to directly address, and attempt to resolve, this long-standing controversy, we will develop a comprehensive, computerized intron database and use it to assess whether the distribution of introns across eukaryotes best fits the tenets of the competing "introns-early" or "introns-late" theories. In addition, we will test five key predictions of these two theories by determining, in various diverse eukaryotes, the intron structure of the gene TPI that has figured most prominently in this controversy. We will also move beyond this debate by using the intron database to evaluate the temporal dynamics of intron gain and loss among the major groups of eukaryotic, especially animals, plants and fungi. Preliminary analyses suggest a highly episodi c pattern, which raises striking mechanistic and selective questions. Finally, we will examine especially recent cases of the apparent insertion or sliding of introns in order to understand how these events occur. ***