Fig. 2

n3 shuffle method. Third codon positions are first categorized into whether they belong to Y, R, H, or N nucleotides, then assigned to the corresponding set (Type vs Set table). Then nucleotides within each set are shuffled (Type vs Shuffle table) to produce the shuffled sequence. Certain nucleotides can belong to two sets (here two nucleotides belong to both H and N) and are shuffled twice