Department of Biochemistry, University of Otago, P,O, Box 56, Dunedin, New Zealand.
Biol Direct. 2012 Jul 13;7:23. doi: 10.1186/1745-6150-7-23.
The problems associated with the RNA world hypothesis are well known. In the following I discuss some of these difficulties, some of the alternative hypotheses that have been proposed, and some of the problems with these alternative models. From a biosynthetic - as well as, arguably, evolutionary - perspective, DNA is a modified RNA, and so the chicken-and-egg dilemma of "which came first?" boils down to a choice between RNA and protein. This is not just a question of cause and effect, but also one of statistical likelihood, as the chance of two such different types of macromolecule arising simultaneously would appear unlikely. The RNA world hypothesis is an example of a 'top down' (or should it be 'present back'?) approach to early evolution: how can we simplify modern biological systems to give a plausible evolutionary pathway that preserves continuity of function? The discovery that RNA possesses catalytic ability provides a potential solution: a single macromolecule could have originally carried out both replication and catalysis. RNA - which constitutes the genome of RNA viruses, and catalyzes peptide synthesis on the ribosome - could have been both the chicken and the egg! However, the following objections have been raised to the RNA world hypothesis: (i) RNA is too complex a molecule to have arisen prebiotically; (ii) RNA is inherently unstable; (iii) catalysis is a relatively rare property of long RNA sequences only; and (iv) the catalytic repertoire of RNA is too limited. I will offer some possible responses to these objections in the light of work by our and other labs. Finally, I will critically discuss an alternative theory to the RNA world hypothesis known as 'proteins first', which holds that proteins either preceded RNA in evolution, or - at the very least - that proteins and RNA coevolved. I will argue that, while theoretically possible, such a hypothesis is probably unprovable, and that the RNA world hypothesis, although far from perfect or complete, is the best we currently have to help understand the backstory to contemporary biology.
与 RNA 世界假说相关的问题是众所周知的。在下面，我将讨论其中的一些困难，一些已经提出的替代假说，以及这些替代模型的一些问题。从生物合成的角度来看——可以说，从进化的角度来看——DNA 是一种修饰后的 RNA，因此“先有鸡还是先有蛋”的两难困境归结为在 RNA 和蛋白质之间做出选择。这不仅是一个因果关系的问题，也是一个统计学可能性的问题，因为两种如此不同类型的大分子同时出现的可能性似乎不大。RNA 世界假说就是一种“自上而下”（或者应该说是“回溯到现在”？）的早期进化方法的例子：我们如何简化现代生物系统，给出一条可行的进化途径，同时保持功能的连续性？RNA 具有催化能力的发现提供了一个潜在的解决方案：一种单一的大分子最初可能同时进行复制和催化。RNA——构成 RNA 病毒的基因组，并在核糖体上催化肽合成——可能既是鸡，也是蛋！然而，人们对 RNA 世界假说提出了以下反对意见：（i）RNA 是一种过于复杂的分子，不可能在生命起源前出现；（ii）RNA 本质上不稳定；（iii）催化作用只是长 RNA 序列中相对罕见的特性；以及（iv）RNA 的催化 repertoire 太有限。根据我们和其他实验室的工作，我将对这些反对意见提出一些可能的回应。最后，我将批判性地讨论一种替代 RNA 世界假说的理论，称为“先有蛋白质”，该理论认为蛋白质在进化中要么先于 RNA 出现，要么——至少——蛋白质和 RNA 是共同进化的。我将认为，虽然从理论上讲是可能的，但这样的假设可能无法证明，而且 RNA 世界假说虽然远非完美或完整，但它是我们目前最能帮助理解当代生物学背景的理论。
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