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Box 1

From: Control of Caenorhabditis elegans germ-line stem-cell cycling speed meets requirements of design to minimize mutation accumulation

Box 1

Simulation setup. Agent-based simulations used to characterize the dependence of pedigree depth on the spatiotemporal profile of cell cycle lengths comprised control of cell cycle length by position along the distal–proximal axis, cell movement through the mitotic and meiotic zones, and eventual differentiation or apoptosis. The spatial domain of the MZ was defined by a lattice of positions that could be occupied by at most one cell at a time. The lattice was rectangular (with length and width that were either predetermined or that were set by parameters over which optimization was performed), or had a shape defined from experimental measurements. The lattice was seeded with a single primordial cell located at the distal end. As this cell divided, its descendants filled the MZ first width-wise and then length-wise, with daughter cells being pushed laterally or proximally as cells behind them (i.e. more distal to them) divided. To mimic the cone-like structure of the gonad, cells at either end of a given row could be displaced in a way that they wrapped around to the other end of the same row (a, red arrow). Once daughter cells were pushed beyond the last MZ row, they exited the mitotic cell cycle and differentiated by entering the meiotic zone. The meiotic zone was modeled as a first-in-first-out queue, with cells entering at the distal end as they left the MZ, and exiting at the proximal end as they underwent apoptosis or matured as an oocyte. The length of the mitotic cell cycle was modeled as a linear gradient, controlled at the distal end of the MZ and at its proximal end by two parameters with value greater than 2.8 h (b, double-ended arrows; some cell cycle fit simulations allowed for a third, more proximal control point shown with a dashed line; see “Results”). Depending on the kind of simulation, cell length values at the control points were allowed to change at various developmental stages (see Table 1); in this case, the cell cycle length was linearly interpolated along the time axis in addition to the space axis.

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