Strange cousins: Molecular alternatives to DNA and RNA provide new insight into the origin of life

Researchers synthesized TNA molecules, and showed that they could have been used as a genetic coder before RNA and certainly before DNA. Has this solved the question of the beginning of life?

Living systems owe their existence to a pair of information-carrying molecules: DNA and RNA. These molecules constitute chemical bases that have two essential properties for life: they are heredity - that is, they can encode and transmit genetic information, on the other hand, they can also change over time, through processes of Darwinian evolution.

The question that has been in dispute for many years is whether heredity and evolution can be carried out by molecules other than DNA and RNA.

John Chaput, a researcher at Arizona State University's (ASU) Institute for Biological Design who recently published a paper in the journal Nature-Chemistry describing the evolution of threose nucleic acids, together with a multidisciplinary team of scientists from England, Belgium and Denmark extended these characteristics to acids Additional nucleus or XNAs.

The group demonstrated for the first time that six natural polymers are able to act as nucleic acids and share information with DNA. One of these XNAs, a molecule known as anhydrohexitol nucleic acid or HNA is capable of directed, unfolded evolution into biologically useful forms.

The results of the study were published in the current issue of Science. The work sheds new light on questions concerning the origin of life and provides a wide range of practical applications for molecular medicine that were not available before.

Nucleic acids that have been engineered in vitro so that they attach to several molecules behave similarly to antibodies - they specialize in precise attachment to their target. "This feature could be good for building new types of diagnostic kits and biological sensors," says Chaput. while noting that XNAs are molecules with a strong effect, but natural enzymes do not recognize them".

Both RNA and DNA imprint their sequences on four nucleotides - essential information that enables the granting of hereditary traits and also provides an essential coded recipe for building proteins from 20 amino acids naturally. The question of exactly how (and when) the use of this system began remains one of the most intriguing and hotly contested areas of biology.
According to one hypothesis, a simple molecule preceded DNA and RNA and served as the original information conduit. The "RNA World" hypothesis suggests that ancient forms of life were based on RNA and simple proteins. This is because of the great versatility of RNA - so that not only is it able to carry genetic information, but it also acts as an accelerator for chemical reactions like an enzyme, and is therefore considered by many to be an important part of pre-cellular life.

However, the spontaneous emergence of RNA through a sequence of random mixing events of primitive chemicals is at least an unlikely event. "This is a big question," says Chaput. "If the world of RNA existed, how did it come to be? Does it form spontaneously or is it the product of something even simpler than RNA?”

The pre-RNA world hypothesis is gaining momentum, mainly through the study of the XNA molecules, which provide reasonable alternatives to the current biological regime and can be used as chemical building blocks until the current manifestation of life. The current study strengthens the hypothesis that something like this might have happened.

The nucleic acid Threose or TNA, is one of the candidates for the role of the critical mediator. "TNA does some interesting things," Chapot says, noting the molecule's ability to bind with RNA through nonparallel base pairing. This property provides a model of how XNAs can transfer information from the pre-RNA world to the RNA world.”

Nucleic acid molecules, including DNA and RNA, are composed of 3 chemical components: a sugar group, a group of three phosphates that constitute the basic structure of the molecule, and combinations of the four nucleic acids. Through changes in the structural components researchers can engineer XNA molecules with unique properties. However, in order for these exotic molecules to function as a first step towards RNA in the prebiotic era, they had to be able to transfer and reproduce their information from the RNA. For this, special enzymes, called polymerases, are required.

Nature produced DNA and RNA polymerases, capable of reading, transcribing and converting transcription into nucleic acid sequences. For XNA molecules, however, no natural polymerase exists. Thus the group, led by Phil Holliger of the MRC in England, painstakingly developed synthetic polymerases that can copy DNA into XNA and other polymerases that can copy XNA into DNA. In the end, the polymerase was able to copy and encode six different genetic systems. The experiments showed that these natural DNA sequences could have been created with the help of the XNA.

These enzymes are used as tools in molecular evolution and have been associated, for example, with the HIV virus and the HEL lysosome. "This is a synthetic Darwinian process," Chaput says. "The same thing happens inside our cells, but it's done in a test tube."

The next step is to use the technology and apply it to the production of unnatural nucleic acids. Only after many such proteins are formed, will it be possible to piece together the puzzle and assess how the process took place at the beginning of life.

to the notice of the researchers