Hachimoji – new building blocks for life?

24 February 2019

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Four new DNA building blocks that meet the criteria to encode life have been created by US scientists...

The secret to life on Earth is found in DNA and its four genetic letters or "bases". These are adenine, cytosine, thymine and guanine, which are shortened to A, C, T and G. The famous "double helix" consists of two complementary strands, each the genetic mirror image of and wound around the other, held in place by interactions between the bases on opposite strands.

While these four bases are sufficient to encode the information for life, could there be more? By modifying the structure of existing bases, Shuichi Hoshika and his colleagues from Firebird Biomolecular Sciences, Florida, have created four brand new bases. These can work alongside the four existing DNA bases to give an 8-letter code. This new system called "Hachimoji" – Japanese for ‘eight’ and ‘letters’ – meets the fundamental criteria to encode life as we know it.

First, these non-standard bases can assemble stable double helices. Indeed, the Florida team was able to predict double helix dissociation rates, a proxy for stability, with error rates comparable to those for standard DNA. Reliable thermodynamics are the first step in showing that Hachimoji could function as an information storage molecule.

The code for life must also be reliably replicated. Hoshika and his colleagues tested whether they could use Hatchimoji DNA as a template to synthesise RNA, the single-stranded molecule which acts as an intermediate between DNA and life’s effectors, proteins. They first identified a protein capable of producing RNA from Hatchimoji DNA. This RNA was bound by a fluorescent protein, whose fluorescence would be disturbed by random incorporation of non-standard bases. This clever trick allowed the authors to conclude that Hachimoji DNA can be copied reliably into RNA.

The third essential feature is mutability. Mutations, or changes, in sequence occur at random, generating variation which is put to the test of natural selection. Without change there can be no evolution. However, mutations should not impair the double helix stability or its replication. The Florida team examined high resolution Hachimoji structures and found that changes in base sequence lead to variation in structure within the range of standard DNA –the Hachimoji system can tolerate changes in sequence. 

The Hachimoji system is revolutionary both in terms of technological opportunities and conceptualisation of life itself. DNA is emerging as an information storage tool beyond biological organisms. Previous work has converted binary into four letter code and allowed us to store and retrieve data ranging from Shakespeare’s sonnets to an Amazon gift card. The four bases of DNA have also been used as signature barcodes in molecular biology. Four additional bases represent a huge leap in coding power.

Essentially all forms of life on earth depend on a sequence of DNA’s four bases. Here, Hoshika and his colleagues have proved four other bases can satisfy the principles governing life as we understand it. Is this the hint of a new life form we could encounter somewhere in the cosmos?

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