5' → 3' synthesis Initiation
DNA polymerases are enzymes that copy DNA by reading a template strand and synthesizing its complement. But what happens when there is no template?
Research by Castle, Gorochowski et al. (Nature Communications, 2026) showed that polymerases, given only free nucleotides and no template, produce structured sequences through a two-stage mechanism they termed "untemplated synthesis" or "doodling."
Stage 1 (Initiation): The enzyme adds nucleotides slowly and stochastically, biased by its own molecular preferences. The output is largely random.
Stage 2 (Amplification): Short repetitive sequences from Stage 1 fold back on themselves, forming hairpin structures. These transient self-templates let the polymerase extend the pattern, creating a positive feedback loop. Structurally stable repeats (palindromic enough to form hairpins) outcompete random sequences.
The dominant motifs depend on temperature, available nucleotides, and the specific polymerase used. GT/TG dinucleotide repeats are the most universal pattern. At 65 °C, AT repeats dominate; at 74 °C, CGTATATA octamers emerge.
This visualization implements a simplified but faithful version of this mechanism, letting you watch structure crystallize from noise in real time.