Fig. 4: Evidence for clonal deceleration from single-cell phylogenies and longitudinal data.

a, b, Effective population size (N_eff) trajectories inferred from single-cell phylogenies in this paper (a) and in Mitchell et al.³⁶, using previously determined HSC population size estimates³³ (b). Dotted lines represent parts of the trajectory with high variance (log(var(N_eff)) > 5). Coal., coalescence. c, Representation of biphasic fit to N_eff estimates and extrapolation from early growth (observed clone size is calculated as the clonal fraction in the phylogeny scaled by an N_eff of 200,000 HSCs × yr; comparison with 1,000,000 HSC × yr in Extended Data Fig. 7e). d, Ratio of observed to expected (extrapolated from early growth) clone size from phylogenies (n = 37 expanded clones detected in haematopoietic phylogenies). e, Representation of extrapolated trajectories derived from longitudinal data, assuming stable lifelong growth at the same fixed rate we observed during older age; some projections are not feasible (that is, they exceed lifetime, with onset pre-conception). f, Relationship between age and observed growth rate of clones and VAF (longitudinal data; light blue represents clones with projected onset within lifetime and golden represents those exceeding lifetime). g, Quantification of unfeasible clones (exceeding lifetime) per gene (longitudinal data, n = 633). Intervals represent the beta-distributed 90% confidence interval. h, Representation of the calculation of minimum (min.) historical growth. i, Ratio of observed to historical (longitudinal data) and late to expected (phylogenetic data) growth (n = 37 clones detected in phylogenies (top); n = 633 in longitudinal data (bottom)). j, Differences between the median observed and historical growth per year for each gene. k, Projected ages at onset for all clones, assuming stable lifelong growth at the same fixed rate we observed during older age. Boxes in d, i, represent the 25th, 50th (median) and 75th percentiles of the data; the whiskers represent the lowest (or highest) datum within 1 interquartile range from the 25th (or 75th) percentile.