调查生命是如何在如此久远的早期地球上出现的,是科学最迷人的挑战之一。更复杂的生命的基本构件必须在哪些条件下才能形成?其中一个主要的答案是基于所谓的RNA世界概念,它是由分子生物学先驱沃尔特-吉尔伯特在1986年提出的。根据这一假说,核苷酸从“原始汤”中产生,短RNA分子由核苷酸产生。这些所谓的寡核苷酸已经能够编码少量的遗传信息。
由于这样的单链RNA分子也可以结合成双链,然而,这就产生了理论上的前景,即这些分子可以自我复制。在每种情况下只有两个核苷酸结合在一起,这意味着一条链是另一条链的完全对应物,从而形成另一条链的模板。
在进化的过程中,这种复制可能会得到改善,并在某个时候产生更复杂的生命。慕尼黑大学化学家Thomas Carell说:“RNA世界的想法有一个很大的优势,它勾勒出了一条路径,复杂的生物大分子,如具有优化催化和同时具有信息编码特性的核酸,可以出现。按照我们今天的理解,遗传物质是由双股DNA组成的,这是一种由核苷酸组成的略经修改的、耐用的大分子形式。”
然而,这一假说并非没有问题。例如,RNS是一个非常脆弱的分子,特别是当它变长时。此外,目前还不清楚RNA分子与蛋白质世界的联系是如何产生的,正如我们所知,遗传物质为其提供了蓝图。正如发表在《自然》杂志上的一篇新论文所述,Carell的工作小组已经发现了一种可能发生这种联系的方式。
RNA本身是一个复杂的大分子。除了编码遗传信息的四个经典碱基A、C、G和U之外,它还包含非经典碱基,其中一些具有非常不同的结构。这些非信息编码的核苷酸对RNA分子的运作非常重要。研究人员目前掌握了120多种这样的修饰过的RNA核苷,大自然将它们纳入了RNA分子。它们极有可能是以前RNA世界的遗留物。
Carell小组现在发现,这些非经典的核苷是关键成分,就像它一样,使RNA世界与蛋白质世界联系起来。据Carell说,这些分子化石中的一些当位于RNA中时,可以用单个氨基酸或甚至小的氨基酸链(肽)来"装饰"自己。当氨基酸或肽碰巧与RNA同时存在于一个溶液中时,这导致了小型嵌合RNA-肽结构。在这样的结构中,与RNA相连的氨基酸和肽随后甚至相互反应,形成越来越大、越来越复杂的肽。“通过这种方式,我们在实验室里创造了可以编码遗传信息的RNA-肽颗粒,甚至形成了加长的肽,”Carell说。
因此,古老的化石核苷有点类似于RNA中的核,形成一个核心,长肽链可以在此基础上生长。在RNA的一些链上,肽甚至在几个点上生长。“那是一个非常令人惊讶的发现,”Carell说。“有可能从来没有一个纯粹的RNA世界,但RNA和肽从一开始就在一个共同的分子中共存。 因此,我们应该把RNA世界的概念扩大到RNA-肽世界的概念。肽和RNA在其进化过程中相互支持,新的想法提出。”
根据新的理论,一开始的一个决定性因素是RNA分子的存在,它可以用氨基酸和肽“装饰”自己,从而将它们连接成更大的肽结构。“RNA慢慢发展成一个不断改进的氨基酸连接催化剂,”Carell说。RNA和肽或蛋白质之间的这种关系一直保持到今天。最重要的RNA催化剂是核糖体,它今天仍然将氨基酸连接成长肽链。作为最复杂的RNA机器之一,它在每个细胞中负责将遗传信息翻译成功能性蛋白质。“因此,RNA-肽世界解决了先有鸡还是先有蛋的问题,"Carell说。“这个新想法创造了一个基础,在这个基础上,生命的起源逐渐变得可以解释。”
One of the most fascinating challenges of science is to investigate how life emerged on Earth so far back in its early days. Under what conditions must the basic components of a more complex life be formed? One of the main answers is based on the so-called concept of RNA world, which was proposed by molecular biology pioneer Walter Gilbert in 1986. According to this hypothesis, nucleotides are produced from “primitive soup” and short RNA molecules are produced by nucleotides. These so-called oligonucleotides have been able to encode a small amount of genetic information.
Because such single-stranded RNA molecules can also be combined into double strands, however, this gives rise to the theoretical prospect that these molecules can replicate themselves. In each case, only two nucleotides are bound together, which means that one chain is the exact counterpart of the other, thus forming a template for the other.
In the process of evolution, this replication may be improved and produce more complex life at some point. Thomas Carell, a chemist at the University of Munich, said: “the idea of RNA World has a big advantage. It outlines a path in which complex biological macromolecules, such as nucleic acids with optimized catalysis and information coding properties, can emerge. As we understand it today, genetic material is made up of double strands of DNA, a slightly modified, durable macromolecular form of nucleotides. “
However, this hypothesis is not without problems. For example, RNS is a very fragile molecule, especially when it gets longer. In addition, it is not clear how the connection between RNA molecules and the protein world is formed, and as we know, genetic material provides a blueprint for it. As reported in a new paper published in the journal Nature, Carell’s team has found a possible way to make such a connection.
RNA itself is a complex macromolecule. In addition to the four classical bases A, C, G and U that encode genetic information, it also contains non-classical bases, some of which have very different structures. These non-informative nucleotides are very important for the operation of RNA molecules. Researchers now know more than 120 of these modified RNA nucleosides, which nature has incorporated into RNA molecules. They are most likely relics of the former RNA world.
Carell’s team has now found that these non-classical nucleosides are key ingredients that, like it, connect the RNA world to the protein world. According to Carell, some of these molecular fossils, when located in RNA, can be decorated with a single amino acid or even a small chain of amino acids (peptides) & quot; itself. When amino acids or peptides happen to exist in the same solution as RNA, this leads to a small chimeric RNA- peptide structure. In such a structure, amino acids and peptides linked to RNA then even react with each other to form larger and more complex peptides. “in this way, we have created RNA- peptide particles that encode genetic information in the laboratory, and even form lengthened peptides,” Carell said.
Therefore, the ancient fossil nucleosides are somewhat similar to the nuclei in RNA, forming a core on which long peptide chains can grow. On some strands of RNA, peptides even grow at several points. “it was a very surprising discovery,” Carell said. “it is possible that there has never been a pure RNA world, but RNA and peptides coexist in a common molecule from the very beginning. Therefore, we should extend the concept of RNA world to the concept of RNA- peptide world. Peptide and RNA support each other in their evolution, and new ideas are put forward. “
According to the new theory, a decisive factor in the beginning is the existence of RNA molecules, which can “decorate” themselves with amino acids and peptides to connect them into larger peptide structures. “RNA has slowly evolved into an ever-improving amino acid linking catalyst,” Carell said. The relationship between RNA and peptides or proteins remains to this day. The most important RNA catalyst is the ribosome, which still connects amino acids to grow peptide chains today. As one of the most complex RNA machines, it is responsible for translating genetic information into functional proteins in each cell. “as a result, the RNA- peptide world solves the problem of chicken or egg, & quot;Carell said. “this new idea creates a foundation on which the origin of life gradually becomes explainable.”