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Title: Structured sequences emerge from random pool when replicated by templated ligation

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America
ORCiD logo [1]; ORCiD logo [2];  [1]; ORCiD logo [3]; ORCiD logo [1]
  1. Ludwig Maximilian Univ. of Munich, Munich (Germany). Systems Biophysics and Center for NanoScience
  2. Brookhaven National Lab. (BNL), Upton, NY (United States). Center for Functional Nanomaterials (CFN)
  3. Univ. of Illinois at Urbana-Champaign, IL (United States). Dept. of Bioengineering; Univ. of Illinois at Urbana-Champaign, IL (United States). Carl R. Woese Institute for Genomic Biology

The central question in the origin of life is to understand how structure can emerge from randomness. The Eigen theory of replication states, for sequences that are copied one base at a time, that the replication fidelity has to surpass an error threshold to avoid that replicated specific sequences become random because of the incorporated replication errors [M. Eigen, Naturwissenschaften 58 (10), 465–523 (1971)]. Here, we showed that linking short oligomers from a random sequence pool in a templated ligation reaction reduced the sequence space of product strands. We started from 12-mer oligonucleotides with two bases in all possible combinations and triggered enzymatic ligation under temperature cycles. Surprisingly, we found the robust creation of long, highly structured sequences with low entropy. At the ligation site, complementary and alternating sequence patterns developed. However, between the ligation sites, we found either an A-rich or a T-rich sequence within a single oligonucleotide. Our modeling suggests that avoidance of hairpins was the likely cause for these two complementary sequence pools. What emerged was a network of complementary sequences that acted both as templates and substrates of the reaction. This self-selecting ligation reaction could be restarted by only a few majority sequences. The findings showed that replication by random templated ligation from a random sequence input will lead to a highly structured, long, and nonrandom sequence pool. This is a favorable starting point for a subsequent Darwinian evolution searching for higher catalytic functions in an RNA world scenario.

Research Organization:
Brookhaven National Lab. (BNL), Upton, NY (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
Grant/Contract Number:
SC0012704
OSTI ID:
1777440
Report Number(s):
BNL-221277-2021-JAAM
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Vol. 118, Issue 8; ISSN 0027-8424
Publisher:
National Academy of SciencesCopyright Statement
Country of Publication:
United States
Language:
English

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