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The origin of molecular evolution required the replication of short oligonucleotides to form longer polymers.<br> Prebiotically plausible oligonucleotide pools tend to contain more of some nucleobases than others. It has been<br> unclear whether this initial bias persists and how it affects replication. To investigate this, we examined the<br> evolution of 12 mer biased short DNA pools using an enzymatic model system. This allowed us to study the<br> long timescales involved in evolution, since it is not yet possible with currently investigated prebiotic replication<br> chemistries. Our analysis using next-generation sequencing from different time points revealed that the initial<br> nucleotide bias of the pool disappeared in the elongated pool after isothermal replication. In contrast, the<br> nucleotide composition at each position in the elongated sequences remained biased and varied with both<br> position and initial bias. Furthermore, we observed the emergence of highly periodic dimer and trimer motifs<br> in the rapidly elongated sequences. This shift in nucleotide composition and the emergence of structure through<br> templated replication could help explain how biased prebiotic pools could undergo molecular evolution and lead<br> to complex functional nucleic acids.