Figure 2. Strand-specific ribonucleotide mapping of chromosome 10.
(a) Top, map of chromosome 10 showing the fraction of end reads mapped to the top strand in bins of 200 base pairs, after background subtraction (see Methods). Origin prediction was complicated at chromosome ends (I) and in other highly repetitive regions (II). Middle, an expanded 200 kbp region of chromosome 10. Excursions (in purple) from the simplest polymerase division of labor (Pol α or δ lagging, Pol ε leading) fall into two classes: unexpected Pol α, δ or ε correspondence (III) and Pol α or δ divergence (IV). Bottom, 100 kbp region of chromosome 10. Inter-origin regions are more (e.g. ARS1012-ARS1014) or less (e.g. ARS1011-ARS1012) symmetrical, depending on fork progression rates and origins firing times. Some origins in the origin database have little effect on ribonucleotide strand bias (e.g. ARS1013), indicating either an incorrect call, minority participation in normally growing cells, unidirectional origin firing, or simply later firing, such that forks proceeding from adjacent origins approach to within current detection thresholds. (b) A stylized chromosome with two replication origins, showing the division of polymerase labor, as predicted from the direction of strand bias transitions at origins (compare with the ARS1012-ARS1014 region above). Roughly three quarters of previously confirmed replication origins (orange diamonds in panel (a); S. cerevisiae OriDB) align with abrupt transitions in strand preference (see Methods for quantitation). This allows algorithmic prediction of origins (black diamonds). ARS1013 was not detected via HydEn-seq. It is indicated (orange diamond) but not labeled.