Researchers at the MRC Laboratory of Molecular Biology, in collaboration with colleagues from the University of Edinburgh, Wrocław University of Science and Technology, and the Polish Academy of Science, have challenged the popular RNA World hypothesis regarding the origin of life on Earth. The work, published in Nature, supports a mixed RNA/DNA model which could serve as a bridge to today’s DNA-centric world.
The RNA world hypothesis was first proposed by the molecular biologist Alexander Rich in 1964, with the term ‘RNA world’ coined by Nobel laureate Walter Gilbert in 1986. It postulates that RNA molecules were the initial building blocks of life in the prebiotic world. This hypothesis is an attractive explanation as RNA has some intrinsic functions which are thought to have been critical for starting life. RNA can catalyse chemical reactions needed for protein synthesis through the use of enzymes called ribozymes, and it can also carry and replicate genetic information, as seen in viruses such as influenza. In contrast, current life is based on a more complex system using DNA, RNA, and protein as the major biological units, with DNA at the centre as the main information-carrying molecule. Thus, a question arises – if the RNA world hypothesis is true, how did life move on from being RNA-based to being DNA-based?
In recent times, another theory for the origin of life has emerged that might provide a more plausible explanation, one without a gap between an RNA and DNA world. This theory proposes a model whereby RNA and DNA co-existed for a period of time as one molecule consisting of parts RNA and parts DNA, which later split into their respective individual units. Research by Xu et al explores this ‘mixed’ origin of life theory.
In previous work published in Nature in 2009, researchers from the same group showed that it is possible to synthesise two of the four units that form the backbone of RNA – cytidine (C) and uridine (U) – from simple molecules such as hydrogen cyanide, under the influence of ultraviolet (UV) light irradiation. Both of these factors would have been abundant on prebiotic Earth.
In their current work, Xu et al look further into the mixed RNA/DNA world theory by identifying a route through which to synthesise two additional molecules that could complete the RNA/DNA origin of life ‘alphabet’ – deoxyadenosine (dA) and deoxyinosine (dI). Deoxyadenosine consists of adenosine (one of the four bases that make up DNA) and deoxygenated ribose sugar. It bonds to other base molecules to form DNA. This adenosine can be converted to inosine, an RNA nucleoside. Synthesising dA and dI uses ribo-aminooxazoline (RAO) as a starting point, which undergoes chemical reactions such as hydrolysis and UV irradiation. Crucially, RAO is also known to be an intermediate involved in the production of C and U. This is evidence that the four ‘letters’ needed for creating a mixed RNA/DNA molecule – C, U, dA and dI – can be made from the same components, at the same time, and under the same reaction conditions.
Moreover, the researchers showed that these four bases can form pairs with each other, at different ratios, resulting in a hybrid RNA/DNA molecule.
Through this work, Xu and colleagues have identified a way to generate all the units required for the creation of a molecule consisting of both RNA and DNA, under realistic prebiotic conditions. This demonstrates compelling evidence in support of the hybrid hypothesis, bringing us a step closer to deciphering how life on Earth might have started.
Written by Hristina Gyurova and edited by Ailie McWhinnie.