Figure 3. Replication origin and mtDNA excision proximity explained by random excision and selection for origin-dense fragments.

(a) The colocalization of replication origins and alignment breakpoint locations due to excisions. Black dots represent the centroids of breakpoint clusters (see Materials and methods), and blue and green shading highlights replication origins and their orientation. Darker black dots are due to overlaps of breakpoints, indicating high densities of breakpoints at these locations. (b) A cumulative plot of the displacements between breakpoint edges and closest origins of replication, where the blue curve shows this enrichment of breakpoints near replication origins (top left, (c)). The orange curve represents a simulation of uniform random alignments placed on the reference genome following the true alignment length distribution in the data (bottom left, (c)). The black curve represents the simulation of alignments between randomly selected perfect repeats ≥11 bp on the reference sequence (bottom right, (c)). The green curve agrees much better with the data (blue) curve, which is the same simulation of random alignments placed on the reference following the length distribution of the data, but with the requirement that these alignments span some portion of a randomly selected origin of replication (top right, (c)). (c) A schematic of the models plotted in (b). Alignments are denoted as arrows, with distances between alignment edges (breakpoints) and replication origins (dotted boxes) as dimension lines. Circled drawings depict that uniformly random alignments are selected in the orange model, whereas alignments conditioned on spanning replication origins are present in the green model.