The newly described chemical reaction would be able to assemble DNA building blocks before life forms and their enzymes exist.
Discovery promotes the theory that life on our planet originated from RNA-DNA mixture.
Chemists from Scripps Research have made a discovery that supports a surprising new view of how life on our planet came to be.
In a study published in the Chemistry Journal Applied Chemistryshowed them that a simple compound called diamidophosphate (DAP), which was probably on Earth before life, could have bound together chemically small DNA building blocks called deoxynucleosides, in parts of primordial DNA.
The finding is the latest in a series of discoveries over the past few years, suggesting the possibility that DNA and its close chemical cousin RNA together originated as products of similar chemical reactions, and that the first self-replicating molecules – the first life forms on earth – were mixtures of the two.
The discovery may also lead to new practical applications in chemistry and biology, but most importantly, it addresses the age-old question of how life on earth originated. In particular, it paves the way for more extensive studies on how self-replicating DNA-RNA mixtures could develop and spread on the primordial earth and eventually sow the more mature biology of modern organisms.
“This finding is an important step toward the development of a detailed chemical model of how the first life forms on Earth originated,” says senior author Ramanarayanan Krishnamurthy, PhD, associate professor of chemistry at Scripps Research.
The finding also shifts the field of chemistry of origin of life away from the hypothesis that has dominated in recent decades: The hypothesis of “RNA World” claims that the first replicators were based on RNA, and that DNA only came into being later as a product of RNA life forms.
Is RNA too tough?
Krishnamurthy and others partly question the RNA World hypothesis because RNA molecules may have been just too “tough” to serve as the first self-replicators.
An RNA strand can attract other individual RNA building blocks, which like to form a kind of mirror image string – each building block in the new string binds to its complementary building block on the original “template” string. If the new string can detach from the template string, and in the same way other new strings can start templating, it has achieved the performance of self-replication that underlies life.
But while RNA strands may be good at forming complementary strands, it is not as good at separating them from strands. Modern organisms make enzymes that can force twin strands of RNA – or DNA – to go their own way, enabling replication, but it is unclear how this could have been done in a world where enzymes did not yet exist.
A chimeric solution
Krishnamurthy and colleagues have shown in recent studies that ‘chimeric’ molecular strands that are part of DNA and partially RNA could possibly circumvent this problem because they can design complementary strands in a less tough way so that they can separate relatively easily.
The chemists have also shown in recent years in widely cited articles that the simple ribonucleoside and deoxynucleoside building blocks, RNA and DNA, respectively, could have formed under the same chemical conditions on the early earth.
In addition, they reported in 2017 that the organic compound DAP could have played the crucial role in altering ribonucleosides and ligating them into the first RNA strands. The new study shows that DAP could do the same with DNA.
“To our surprise, we found that the use of DAP to react with deoxynucleosides works better when the deoxynucleosides are not all the same, but rather mixtures of different DNA letters such as A and T, or G and C, such as true DNA. ”Says first author Eddy Jiménez, PhD, a fellow postdoctoral researcher at the Krishnamurthy Laboratory.
Now that we better understand how primordial chemistry could make the first RNAs and DNAs, we can start using them on mixtures of ribonucleoside and deoxynucleoside building blocks to see which chimeric molecules are formed – and whether they can replicate and develop on their own. ”Says Krishnamurthy.
He notes that the work can also have broad practical applications. The artificial synthesis of DNA and RNA – for example in the underlying “PCR” technique COVID-19 tests – comes down to a large global enterprise, but depends on enzymes that are relatively fragile and therefore have many limitations. Robust, enzyme-free chemical methods of making DNA and RNA can be more attractive in many contexts, says Krishnamurthy.
Reference: “Prebiotic phosphorylation and concomitant oligomerization of deoxynucleosides to form DNA” by Eddy Jiménez, Clémentine Gibard and Ramanarayanan Krishnamurthy, 15 December 2020, Applied Chemistry.
DOI: 10.1002 / anie.202015910
Funding was provided by the Simons Foundation.