Before DNA-containing living beings colonized the earth, a wide variety of simple RNA molecules already existed on the prehistoric earth. Researchers have now recreated in the laboratory the conditions under which these RNA molecules acquired the ability to improve one another. These conditions mark the beginning of evolution towards more complex living beings. According to this, evolution began at the molecular level long before cells existed, with individual RNA enzymes reliably copying other RNA molecules. With this knowledge, the former “RNA world” could now be recreated in the laboratory.
Life on Earth developed billions of years ago from just a few tiny building blocks of life. Long before cells existed, they already contained various RNA molecules. During an era in Earth’s history, these dominated terrestrial life, according to the common scientific theory of the “RNA world”. Some of these RNA molecules took over the task of later DNA by storing genetic information and passing it on from generation to generation. Other RNA molecules, like the later evolving proteins, functioned as enzymes that catalyze and accelerate biochemical reactions. Such RNA enzymes are also called ribozymes and still exist to a lesser extent today. But what role did they play in the “RNA world” of that time?
Evolution of RNA molecules
A team led by Nikolaos Papastavrou from the Salk Institute in California has now examined this in more detail. “We are tracking the beginning of evolution,” says senior author Gerald Joyce, also of the Salk Institute. “We asked ourselves when life acquired the ability to improve itself,” adds Papastavrou. Specifically, the researchers analyzed what conditions were necessary for individual RNA molecules to develop further so that optimized life building blocks could emerge from them. To do this, the researchers developed an RNA enzyme whose task is to catalyze the replication of other RNA molecules: a so-called RNA polymerase. This ribozyme was initially very simple, could only copy short RNA strands and made many mistakes. Based on this, Papastavrou and his colleagues gradually modified the RNA enzyme using the method of directed evolution. Dozens of rounds of mutation and selection resulted in enzyme variants that were able to do their job better and better and with fewer errors.
This showed that from a certain point onwards, the RNA enzyme was optimized to such an extent that it could also reliably copy longer RNA molecules. However, there remained an error rate of around ten percent, which still allowed beneficial variations and mutations in the copied object. The copied RNA sequence changed in the course of several rounds of copying, so that this second RNA molecule was ultimately able to fulfill its own function better, as the researchers report. However, if the researchers used the original, non-optimized, unreliable RNA polymerase, the RNA sequence it copied lost its function over time because it accumulated too many mutations.
Co-evolution laid the foundation for today’s living beings
Overall, the study suggests that an “RNA world” actually once existed on the prehistoric Earth in which the evolution of RNA enzymes and other RNA molecules ran in parallel. Without RNA polymerases with high accuracy and low error tolerance, no more highly developed RNA molecules would have emerged, and without the evolution of RNA there would have been no higher living beings made up of more complex molecules and cells, including humans. “By uncovering these novel capabilities of RNA, we uncover the potential origins of life itself and show how simple molecules may have paved the way for the complexity and diversity of life we see today,” explains Joyce.
Based on the findings, Papastavrou and his colleagues hope that the former RNA-based ancient creatures could now be reconstructed in the laboratory. This could then provide further insights into the beginning of life on Earth or even other planets. These follow-up studies could then also clarify which environmental conditions on the prehistoric Earth could have fueled the development of the “RNA world”.
Source: Nikolaos Papastavrou (Salk Institute) et al., Proceedings of the National Academy of Sciences (PNAS), doi: 10.1073/pnas.2321592121