Newly described chemical reactions could have put together building blocks of DNA before life forms and their enzymes existed.
SCRIPPS RESEARCH INSTITUTE
LA JOLLA, CA – Scripps Research chemists made a discovery that supports a surprising new view of how life came about on our planet.
In a study published in the chemistry journal Angewandte Chemie, they showed that a simple compound called diamidophosphate (DAP), which plausibly existed on Earth before life began, chemically assembled tiny building blocks of DNA called deoxynucleosides into strands of primordial DNA could.
The result is the latest in a series of discoveries in recent years that suggest the possibility that DNA and its close chemical kin RNA may have arisen together as the products of similar chemical reactions and that the first self-replicating molecules – first life – form on earth – were mixtures of the two.
The discovery may also lead to new practical applications in chemistry and biology, but its main meaning is that it addresses the age-old question of how life on earth first came about. In particular, it paves the way for more extensive studies of how self-replicating DNA-RNA mixtures could have evolved and spread on primeval Earth, and ultimately spawned the more mature biology of modern organisms.
"This finding is an important step in developing a detailed chemical model of the formation of the first life forms on earth," says lead author of the study, Ramanarayanan Krishnamurthy, PhD, associate professor of chemistry at Scripps Research.
The result also repels the field of chemistry of the origin of life from the hypothesis that has dominated it in recent decades: The “RNA World” hypothesis assumes that the first replicators were based on RNA and that DNA was only later as a product originated from RNA life forms.
Is RNA Too Sticky?
Krishnamurthy and others have questioned the RNA world hypothesis in part because RNA molecules may simply have been too "sticky" to serve as initial self-replicators.
An RNA strand can attract other individual RNA building blocks that adhere to it and form a kind of mirror image strand – each building block in the new strand binds to its complementary building block on the original “template” strand. When the new strand can detach itself from the template strand and begin templating other new strands in the same way, it has accomplished the feat of self-replication that underlies life.
While strands of RNA are good at templating complementary strands, they are not so good at separating from those strands. Modern organisms make enzymes that can force twin strands of RNA – or DNA – to go separate ways, thereby enabling replication. However, it is unclear how this could have happened in a world where enzymes did not yet exist.
A chimeric workaround
Krishnamurthy and colleagues have shown in recent studies that “chimeric” molecular strands that are partial DNA and partial RNA could potentially circumvent this problem, because they can template complementary strands in a less sticky way that allows them to relative easy to separate.
In recent years, chemists have shown in frequently cited publications that the simple ribonucleoside and deoxynucleoside building blocks of RNA and DNA could have been formed under very similar chemical conditions on early Earth.
They also reported in 2017 that the organic compound DAP may have played the crucial role in modifying ribonucleosides and stringing them together to form the first strands of RNA. The new study shows that DAP could have done the same for DNA under similar conditions.
“To our surprise, we found that using DAP to react with deoxynucleosides works better when the deoxynucleosides are not all the same, but mixtures of different DNA letters like A and T or G and C like real DNA. Says lead author Eddy Jiménez, PhD, a postdoctoral fellow in the Krishnamurthy laboratory.
“Now that we have a better understanding of how primordial chemistry could have made the first RNAs and DNAs, we can use them to mix ribonucleoside and deoxynucleoside building blocks to see which chimeric molecules are formed – and whether they replicate themselves and can develop. Says Krishnamurthy.
He notes that the work can also have wide practical applications. The artificial synthesis of DNA and RNA – for example in the "PCR" technique on which COVID-19 tests are based – is a huge global business, but it depends on enzymes, which are relatively fragile and therefore have many limitations. According to Krishnamurthy, robust, enzyme-free chemical methods for making DNA and RNA could be more attractive in many contexts.
"Prebiotic phosphorylation and simultaneous oligomerization of deoxynucleosides to form DNA" was written by Eddy Jiménez, Clémentine Gibard, and Ramanarayanan Krishnamurthy. Financing was provided by the Simons Foundation.