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？地球大约是在45亿年前形成的，有充分的证据表明，生命已经存在了至少35亿年。在古代地球的某个时刻，从化学（简单分子在热力学定律下的反应）到生物学（控制自身复制的复杂分子）发生了转变。关于生命起源，最被广泛接受的观点是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，在生命起源中起着至关重要的作用。RNA链可以作为互补链合成的模板，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，可以作为控制化学反应速率的催化剂。具有催化作用的RNA被称为核酶。实验室实验已经开发出核糖酶序列，这些序列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，这些实验为RNA世界的概念提供了支持。这项研究计划的总体目标是发展一种全面的理论，说明生命是如何从生命起源前的化学混合物进化到单细胞生物阶段的。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本分析相联系。我们将回答以下问题。在什么条件下，益生元化学反应可以产生足够长的随机RNA序列来充当核酶？生物学中使用的特定种类的聚合物是如何从我们期望由化学产生的各种分子混合物中产生的？自我复制的核酶是如何产生的？核酶系统是如何进化成我们今天看到的细胞生物的？在过去的十年里，人们已经清楚地认识到，有许多其他的恒星也有自己的行星系统；因此，宇宙中还有许多其他地方可能存在生命。我们的工作旨在揭示地球上从化学中产生生物的难易程度，以及我们有一天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.