XNA: The Next Evolution in the DNA Science Revolution

For millennia, humans have contemplated the origins of life. Historically, concepts such as spontaneous generation were accepted by many Europeans, suggesting house flies could arise from decomposing matter and aphids from dew droplets. Today, these thoughts are consigned to the past; instead, advancements in genetics are providing contemporary insight into how the tree of life germinated. These discoveries are important, for they provide an opportunity to witness what processes may have initiated the molecular make-up of organic structures even more ancient than our most distant biological forebears; and a humble opportunity to remind us of our place in the natural world.

Living organisms are made of cells, which consist of an outer membrane that encloses a soup-like fluid, or cytoplasm, of specialized structures that enable the cell to function. At the center of many cell types is the nucleus, which contains genetic material, or DNA, that is inherited from your parents; this genetic code determines your characteristics.

Resembling a spiral-staircase, a DNA strand is a long molecular chain consisting of a sugar-phosphate framework that supports a sequence of paired struts, or bases, that always join to form either an A-T or a C-G configuration. The combinations of these base-pairs are important because they are interpreted by RNA (a molecule associated with DNA), which can replicate and translate the code into a sequence of amino acids, the raw ingredients of proteins. Proteins are the building blocks of life, forming cellular structures, enzymes, hormones, and so on; so these molecular processes are drivers for assembling the bodies of plants and animals. The arrangement of paired-bases on the struts of the genetic-ladder, however, can be altered through sexual reproduction or mutation; this affects the nature of the subsequent proteins that are formed, which can change the characteristics of an individual organism, leading to variation within species’ and thus provide opportunities for Natural Selection.

According to the fossil record, the ancestors of modern humans lived in Eastern Africa around 2.4 million years ago; the predecessors of the first flowering plants sprouted during the early Cretaceous, 130 million years ago; primitive jawless fishes left their first records within rock stratum of the Cambrian seas, a little over 530 million years ago; and the first records of any cellular life-form date from around 3.5 billion years ago. Venture even further back in time and you enter the realm of organic molecules, some of which assembled to form the first cells. Although it is DNA that now stores genetic information, it is accepted by many scientists that RNA arose first due to its simpler structure. These early RNAs would have interacted with other proto-molecules, eventually leading to the development of DNA, in an ancient aquatic system – the so called primordial soup. Once enveloped by a membrane, these ancient biochemical structures would have functioned like a primitive cell.

Since the structure of DNA was discovered in 1953, ample research has been conducted on its behaviour. This has included changing the paired-base sequences to observe any outcomes in the subsequent proteins that form. Recently, however, a paper in the journal Science provides fascinating new evidence that may take us a step closer to the dawn of life.

The UK Medical Research Council's Laboratory of Molecular Biology has manipulated the sugar-phosphate backbone that supports DNA. These trials involved synthesizing xeno-nucleic acids, or XNAs, which are similar to DNA or RNA, yet have a modified sugar-phosphate framework. The strut-like base pairs, however, were not altered, allowing the XNA to interact and link-up with organic DNA or RNA. In order to synthesises proteins, normal DNA is unfastened by an enzyme called polymerases, which allows the RNA to transcribe the DNA code for protein production. However, the Research Council’s Laboratory has developed a polymerases enzyme that can work with both DNA and XNA to determine the sequence of proteins. This is an example of synthetic genetics that can exhibit hereditary behaviour in the laboratory, rather than in living organisms.

The new XNA molecules reveal that the biochemistry that characterizes organic DNA does not need to be replicated for synthesizing similar molecules that function in a comparable manner. This indicates other molecules could have behaved in a similar way to RNA or DNA when the primeval earth was devoid of life. These ancient molecules may have had the ability to pass chemical sequences from one molecule to the next, by replicating one another; during such replication, however, changes in the chemical makeup, caused by radiation or other chemicals, would have led to variation within the molecular community. Passing information from one generation to the next, with the inclusion of mutations to give rise to variation, is in essence Darwin’s theory: expressed beneficial changes within the molecular community could allow for the precursors of Natural Selection.

This type of science needs to be carefully regulated to ensure there is no harm to living systems and that there are no negative implications for future generations. Despite this, these discoveries not only contribute to advances in genetics and biotechnology; they demonstrate how the fundamental components of all organisms – bacteria, oak trees, mushrooms, centipedes, humans – can exist separate from biological systems, and provide evidence for how proto-organic structures may have behaved prior to the development of the first cells and the stable environments they offer. These advances also support the concept of Natural Selection and the complex, stunningly beautiful and elegant mechanisms that have enabled the great progression of life to diverge and diversify throughout the history of our earth – the origin of all family trees, including our own. 

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Jonathan Booth

BSc in Marine Biology, MSc in Sustainable Engineering and PGCE/MEd in Secondary Science. Travelled and worked across East Asia, Oceania, the Middle East and Africa.

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