The stability of sequence replication was crucial for the emergence of molecular evolution and early life. Exponential replication with a first-order growth dynamics show inherent instabilities such as the error catastrophe and the dominance by the fastest replicators. This favors less structured and short sequences. The theoretical concept of hypercycles has been proposed to solve these problems. Their higher-order growth kinetics leads to frequency-dependent selection and stabilizes the replication of majority molecules. However, many implementations of hypercycles are unstable or require special sequenceswith catalytic activity . Here, we demonstrate the spontaneous emergence of higher-order cooperative replication from a network of simple ligationchain reactions (LCR). We performed long-term LCR experiments from a mixture of sequences under molecule degrading conditions with a ligase protein. At the chosen temperature cycling, a network of positive feedback loops arose from both the cooperative ligation of matching sequences and the emerging increase in sequence length. It generated higher-order replication with frequency-dependent selection. The experiments matched a complete simulation using experimentally determined ligation rates and the hypercycle mechanism was also confirmed by abstracted modeling. Since templated ligation is a most basic reaction of oligonucleotides, the described mechanism could have been implemented under microthermal convection on early Earth .
Each living species carries a complex DNA sequence that determines their unique features and functionalities. It is generally assumed that life started from a random pool of oligonucleotides sequences, generated by a prebiotic polymerization of nucleotides. The mechanism that initially facilitated the emergence of sequences that code for the function of the first species from such a random pool of sequences remains unknown. It is a central problem of the origin of life. An interesting option would be a self-selection mechanism by spontaneous symmetry breaking. Initial concentration fluctuations of specific sequence motifs would have been amplified and outcompeted less abundant sequences, enhancing the signal to noise to replicate and select functional sequences . Here, we demonstrate with experimental and theoretical findings that templated ligation would provide such a self-selection. In templated ligation, two adjacent single sequences strands are chemically joined when a third complementary strand sequence brought them in close proximity. This simple mechanism was a likely side-product of a prebiotic polymerization chemistry once the strands reach the length to form double stranded species. As shown here, the ligation gave rise to a nonlinear replication process by the cooperative ligation of matching sequences which self-promoted their own elongation. This led to a cascade of enhanced template binding and faster ligation reactions. A requirement was the reshuffling of the strands by thermal cycling, enabled for example by microscale convection. Assuming that templated ligation was driven by the same chemical mechanism that generated prebiotic polymerization of oligonucleotides, the mechanism could function as a missing link between polymerization and the self-stabilized replication, offering a pathway to the autonomous emergence of Darwinian evolution for the origin of life .
R
The stability of sequence replication was crucial for the emergence of molecular evolution and early life. Exponential replication with a first-order growth dynamics show inherent instabilities such as the error catastrophe and the dominance by the fastest replicators. This favors less structured and short sequences. The theoretical concept of hypercycles has been proposed to solve these problems. Their higher-order growth kinetics leads to frequency-dependent selection and stabilizes the replication of majority molecules. However, many implementations of hypercycles are unstable or require special sequenceswith catalytic activity
Each living species carries a complex DNA sequence that determines their unique features and functionalities. It is generally assumed that life started from a random pool of oligonucleotides sequences, generated by a prebiotic polymerization of nucleotides. The mechanism that initially facilitated the emergence of sequences that code for the function of the first species from such a random pool of sequences remains unknown. It is a central problem of the origin of life. An interesting option would be a self-selection mechanism by spontaneous symmetry breaking. Initial concentration fluctuations of specific sequence motifs would have been amplified and outcompeted less abundant sequences, enhancing the signal to noise to replicate and select functional sequences
R
the spontaneous emergence of higher-order cooperative replication from a network of simple ligationchain reactions (LCR). We performed long-term LCR experiments from a mixture of sequences under molecule degrading conditions with a ligase protein. At the chosen temperature cycling,
with experimental and theoretical findings that templated ligation would provide such a self-selection. In templated ligation, two adjacent single sequences strands are chemically joined when a third complementary strand sequence brought them in close proximity. This simple mechanism was a likely side-product of
R
network of positive feedback loops arose from both
prebiotic polymerization chemistry once the strands reach the length to form double stranded species. As shown here, the ligation gave rise to a nonlinear replication process by
R
and the emerging increase in sequence length. It generated higher-order replication with frequency-dependent selection. The experiments matched a complete simulation using experimentally determined ligation rates and the hypercycle mechanism was also confirmed by abstracted modeling. Since templated ligation is a most basic reaction
which self-promoted their own elongation. This led to a cascade of enhanced template binding and faster ligation reactions. A requirement was the reshuffling of the strands by thermal cycling, enabled for example by microscale convection. Assuming that templated ligation was driven by the same chemical mechanism that generated prebiotic polymerization
R
described mechanism could have been implemented under microthermal convection on early Earth
mechanism could function as a missing link between polymerization and the self-stabilized replication, offering a pathway to the autonomous emergence of Darwinian evolution for the origin of life