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Non-complementary strand commutation as a fundamental alternative for information processing by DNA and gene regulation

Abstract

The discovery of the DNA double helix has revolutionized our understanding of data processing in living systems, with the complementarity of the two DNA strands providing a reliable mechanism for the storage of hereditary information. Here I reveal the ‘strand commutation’ phenomenon—a fundamentally different mechanism of information storage and processing by DNA/RNA based on the reversible low-affinity interactions of essentially non-complementary nucleic acids. I demonstrate this mechanism by constructing a memory circuit, a 5-min square-root circuit for 4-bit inputs comprising only nine processing ssDNAs, simulating a 572-input AND gate (surpassing the bitness of current electronic computers), and elementary algebra systems with continuously changing variables. Most importantly, I show potential pathways of gene regulation with strands of maximum non-complementarity to the gene sequence that may be key to the reduction of off-target therapeutic effects. This Article uncovers the information-processing power of the low-affinity interactions that may underlie major processes in an organism—from short-term memory to cancer, ageing and evolution.

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Fig. 1: Signal transduction—conventional complementarity paradigm versus non-complementary strand commutation.
Fig. 2: Design and performance of the basic logic gates.
Fig. 3: Performance aspects of the basic YES/OR logic gates.
Fig. 4: Memory circuit and its design and performance.
Fig. 5: Square-root circuit and its design and performance.
Fig. 6: High bitness systems—500-input and 572-input AND gates.
Fig. 7: Analogue systems solving elementary algebra problems.
Fig. 8: Gene regulation circuits, and the strand commutation mechanism versus the conventional antisense concept.

Data availability

The data that support the findings of this study are provided in the Article and its Supplementary Information, and are also available from the author on request. Source data are provided with this paper.

Code availability

The NUPACK (Ubuntu 14.04 BASH) and MATLAB scripts used to design the systems and analyse their performance are too numerous to be readily shared publicly, but can be made available from the corresponding author on reasonable request.

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Acknowledgements

I express deep gratitude to all developers of and contributors to the NUPACK algorithm, without which this study would be far less comprehensive. I thank I. L. Nikitina for assistance with manuscript preparation and the Cell Technologies Center core facility of the Institute of Cytology of the Russian Academy of Sciences for the confocal images in Figs. 4 and 5.

Author information

Authors and Affiliations

Authors

Contributions

M.P.N. conceived the idea, designed and performed the study, and wrote the manuscript.

Corresponding author

Correspondence to Maxim P. Nikitin.

Ethics declarations

Competing interests

M.P.N. has filed patent applications RU2019145384 (granted) and PCT/RU2020/050402 covering aspects of these findings. M.P.N. is the founder of the Abisense company, which manufacturers the LumoTrace bioimaging system.

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Peer review information

Nature Chemistry thanks Anne Condon, Grigory Tikhomirov and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary Note 1, Figs. 1–17 and Table 1.

Reporting Summary

Source data

Source Data Fig. 1

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Statistical source data.

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Statistical source data.

Source Data Fig. 4

Statistical source data.

Source Data Fig. 5

Statistical source data.

Source Data Fig. 6

Statistical source data.

Source Data Fig. 7

Statistical source data.

Source Data Fig. 8

Statistical source data and unprocessed gels.

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Nikitin, M.P. Non-complementary strand commutation as a fundamental alternative for information processing by DNA and gene regulation. Nat. Chem. 15, 70–82 (2023). https://doi.org/10.1038/s41557-022-01111-y

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