were lower or higher than observed values. The P values were computed as the proportion of bootstrap samples that exceeded the observed values. The fold change of average L and S was computed as a ratio of observed values to the average of sampled values. We tested all 12,563 GO terms that included more than one gene. The P-value significance threshold was thus ~2 × 10−6. The enrichment and depletion of pLOF variants in public gene databases was tested in a similar way.