Molecular Mechanisms for the Origin of Life and the RNA World

这一提议解决了跨学科科学研究中最重要的问题之一--生命是如何开始的？地球大约形成于45亿年前，有很好的证据表明生命至少存在了35亿年。在古代地球上的某个时候，从化学(根据热力学定律进行反应的简单分子)过渡到生物(控制自身复制的复杂分子)。关于生命起源的最广泛接受的观点是RNA世界假说，该假说认为RNA或某种与RNA非常相似的核酸聚合物在生命起源中发挥了重要作用。RNA链可以作为合成互补链的模板，因此，它可以作为存储信息的基因。RNA链也可以折叠成特定的三维结构，这些结构可以作为催化剂来控制化学反应的速度。催化的核糖核酸称为核酶。实验室实验已经开发出能够执行生命起源时自我复制RNA系统所需的一些基本任务的核酶序列，这些实验支持RNA世界的概念。这项研究计划的总体目标是开发一种全面的理论，说明生命是如何从益生菌化学混合物中出现并进化到单细胞生物体阶段的。许多关键问题都是概念性的问题，适合于计算机模拟和数学模型。我们将设计我们的模型，使它们与实验室实验和地质样品分析相联系。我们将解决以下问题。在什么条件下，益生菌化学反应可以产生随机的RNA序列，其长度足以充当核酶？生物使用的特定类型的聚合物是如何从我们期望通过化学产生的各种分子混合物中出现的？自我复制核酶是如何产生的？核酶系统是如何进化成我们今天所看到的那种细胞生物的？在过去的十年里，很明显，还有许多其他恒星拥有自己的行星系统；因此，宇宙中还有许多其他地方可能存在生命。我们的工作旨在阐明生物在地球上从化学中产生是容易还是困难，因此我们有一天可能在另一个星球上发现生命的可能性有多大。

This proposal addresses one of the foremost issues in interdisciplinary science research - How did life start? The Earth was formed about four and a half billion years ago, and there is good evidence that life has been present for at least three and half billion years. At some point on the ancient Earth there was a transition from chemistry (simple molecules reacting under the laws of thermodynamics) to biology (complex molecules that control their own replication). The most widely accepted idea for the origin of life is the RNA World hypothesis, which states that RNA, or some kind of nucleic acid polymer very similar to RNA, played an essential role in the origin of life. An RNA strand can act as a template for synthesis of a complementary strand, and for this reason, it can act as a gene that stores information. An RNA strand can also fold to specific three dimensional structures that can act as catalysts that control the rate of chemical reactions. A catalytic RNA is called a ribozyme. Laboratory experiments have developed ribozyme sequences that are able to carry out some of the essential tasks that would be required in a self-replicating RNA system at the time of the origin of life, and these experiments lend support to the RNA World concept. The overall objective of this research program is to develop a comprehensive theory of the way life emerged from a prebiotic chemical mixture and evolved to the stage of single celled organisms. Many of the key issues are conceptual ones that lend themselves to computer simulations and mathematical models. We will design our models so that they have a link to laboratory experiments and to analysis of geological samples. We will address the following questions. Under what conditions can prebiotic chemical reactions generate random sequences of RNA that are long enough to act as ribozymes? How do the specific kinds of polymer used by biology emerge from the diverse mixtures of molecules that we would expect to be generated by chemistry? How did self-replicating ribozymes arise? How did ribozyme systems evolve toward the kind of cellular organisms that we see today? Over the past decade it has become clear that there are many other stars with their own planetary systems; and hence there are many other places in the universe where life could potentially exist. Our work aims to shed light on just how easy or difficult it is for biology to emerge from chemistry on our Earth, and hence how likely it is that we might one day find life on another planet.