Replication elongates short DNA, reduces sequence bias, and develops trimer structure

Abstract

The origin of molecular evolution required the replication of short oligonucleotides to form longer polymers. Prebiotically plausible oligonucleotide pools tend to contain more of some nucleotide bases than others. It has been unclear whether this initial bias persists and how it affects replication. To investigate this, we examined the evolution of 12 mer biased short DNA pools during enzymatic templated polymerization. Our analysis using next-generation sequencing from different time points revealed that the initial nucleotide bias of the pool disappeared in the elongated pool after isothermal replication. In contrast, the nucleotide composition at each position in the elongated sequences remained biased and varied with both position and initial bias. Furthermore, we observed the emergence of highly periodic dimer and trimer motifs in the rapidly elongated sequences. This shift in nucleotide composition and the emergence of structure through templated replication could help explain how biased prebiotic pools could undergo molecular evolution and lead to complex functional nucleic acids.