Preprint Hypothesis Version 10 Preserved in Portico This version is not peer-reviewed

Who is the “Matchmaker” between Proteins and Nucleic Acids?

Version 1 : Received: 28 March 2020 / Approved: 29 March 2020 / Online: 29 March 2020 (04:08:22 CEST)
Version 2 : Received: 1 April 2020 / Approved: 2 April 2020 / Online: 2 April 2020 (05:16:09 CEST)
Version 3 : Received: 17 April 2020 / Approved: 19 April 2020 / Online: 19 April 2020 (04:00:24 CEST)
Version 4 : Received: 11 July 2020 / Approved: 12 July 2020 / Online: 12 July 2020 (14:28:35 CEST)
Version 5 : Received: 26 July 2020 / Approved: 26 July 2020 / Online: 26 July 2020 (17:40:23 CEST)
Version 6 : Received: 6 August 2020 / Approved: 7 August 2020 / Online: 7 August 2020 (06:53:34 CEST)
Version 7 : Received: 16 August 2020 / Approved: 20 August 2020 / Online: 20 August 2020 (08:54:53 CEST)
Version 8 : Received: 30 August 2020 / Approved: 31 August 2020 / Online: 31 August 2020 (08:05:13 CEST)
Version 9 : Received: 9 September 2020 / Approved: 11 September 2020 / Online: 11 September 2020 (08:39:39 CEST)
Version 10 : Received: 28 January 2021 / Approved: 29 January 2021 / Online: 29 January 2021 (15:26:13 CET)

A peer-reviewed article of this Preprint also exists.

Xie P. 2021. Who is the missing “matchmaker” between proteins and nucleic acids?, The Innovation 2(3), 100120 (DOI: Xie P. 2021. Who is the missing “matchmaker” between proteins and nucleic acids?, The Innovation 2(3), 100120 (DOI:


A plenty of theories on the origin of genetic codes have been proposed so far, yet all ignored the energetic driving force, its relation to the biochemical system, and most importantly, the missing “matchmaker” between proteins and nucleic acids. Here, a new hypothesis is proposed, according to which ATP is at the origin of the primordial genetic code by driving the coevolution of the genetic code with the pristine biochemical system. This hypothesis aims to show how the genetic code was produced e.g. by photochemical reactions in a protocell that derived from a lipid vesicle enclosing various life’s building blocks (e.g. nucleotides and peptides). At extant cell, ATP is the only energetic product of photosynthesis, and is at the energetic heart of the biochemical systems. ATP could energetically form and elongate chains of both polynucleotides and polypeptides, thus acting a “matchmaker” between these two bio-polymers and eventually mediating precellular biochemical innovation from energy transformation to informatization. ATP was not the only one that could drive the formation of polynucleotides and polypeptides, but favored by precellular selection. The protocell innovated a photosynthetic system to produce ATP efficiently and regularly with the aids of proteins and RNA/DNA. The completion of permanently recording the genetic information by DNA marked the dawn of cellular life operated by Darwinian evolution. The ATP hypothesis assumes or supports the photochemical origin of life, shedding light on the origins of both photosynthetic and biochemical systems, which remain largely unknown thus far. Based on the ATP hypothesis, virus (like the new coronavirus) could not be the earliest life on Earth, as it has neither biochemical systems nor lipid bilayer membrane that provided relatively isolated environment for the development of protobiochemical reactions, although it owns the genetic code of a cellular life. Virus could not be a bridge between life and non-life, but is an anti-life substance, as it depletes cellular material for its own replication, and then spreads by destroying the host cells. It can be imagined that if cellular life are completely wiped out by the virus, the complete destruction of life on Earth would be inevitable.


The ATP hypothesis; the origin of the genetic code; life’s building block; probiotic “soup”; from lipid vesicles to protocells; coevolution; primordial biochemical system; missing “matchmaker”; energy transformation; informatization; structuralization; precellular selection; photo- chemical origin of life, virus; anti-life form; 2019-nCoV


Biology and Life Sciences, Biochemistry and Molecular Biology

Comments (1)

Comment 1
Received: 29 January 2021
Commenter: Ping Xie
Commenter's Conflict of Interests: Author
Comment: In this version, I changed the title of the manuscript, and  most importantly, modified (beautify) all figures.  Minor corrections of the text were also made.
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