Figure 4. Past generation times corresponding to the observed polymorphism ratios in CEU, given parental age effects estimated from de novo mutation (DNM) data.

Red points represent the point estimates based on maximum likelihood estimators of mutation parameters from the DNM data; gray dots show estimates from 500 bootstrap replicates by resampling trios with replacement. We assumed the same male to female generation times (Gp = Gm) for all time windows. Similar trends were obtained for other fixed values of Gp/Gm (between 0.8–1.2) or independently varying Gp and Gm (Figure 4—figure supplement 1, Figure 4—figure supplement 3).

Figure 4—figure supplement 1. Past generation times corresponding to the observed pairwise polymorphism ratios, assuming fixed ratio of male to female generation times of 0.8 (A), 1.1 (B), and 1.2 (C).

The parental age effects were inferred from de novo mutation (DNM) data of 2879 Icelandic trios from Halldorsson et al., 2019.

Figure 4—figure supplement 2. Past generation times corresponding to the observed pairwise polymorphism ratios, based on parental age effects estimated from an earlier de novo mutation (DNM) data (Jónsson et al., 2017).

In each panel, the ratio of male to female generation times is assumed to be fixed throughout time at 0.8 (A), 1 (B) and 1.2 (C), respectively.

Figure 4—figure supplement 3. Combinations of paternal and maternal reproductive ages corresponding to the observed pairwise polymorphism ratios.

Under the assumption of linear parental age effects on the mutation rate of each mutation type, a specific value of pairwise polymorphism ratio places a linear constraint on the values of paternal and maternal reproductive ages (denoted by Gp and Gm), which is represented by a line in each plot. Blue lines represent predicted constraints based on the maximum likelihood estimators of mutation parameters estimated from de novo mutation (DNM) data (Halldorsson et al., 2019); gray lines show constraints from 500 bootstrap replicates by resampling trios with replacement. Panels (A) and (B) show the same results but with Gm and Gp shown on the x- and y-axes, respectively, in order to illustrate their temporal trends. Consistent with results shown in Figure 3—figure supplement 3, the nonTpG T>C/T>G and non-CpG C>T/C>A ratios are relatively insensitive to Gm and largely determined by Gp, so the temporal trends of these two mutation ratios in panel (B) mirror those of Figure 4. The C>G/T>A depends on both Gp and Gm, so its temporal trend in both panels (A) and (B) mirrors that shown in Figure 4. Note that for each time window the gray areas predicted by three polymorphism ratios barely, if at all, overlap, suggesting that no combination of (Gp, Gm) values can explain the three observed polymorphism ratios simultaneously. In addition, the temporal trends predicted by the three polymorphism ratios disagree with each other.