a, Relationship between tissue- and time-specificity. Gene developmental profiles illustrate the extremes of the indexes, which range from 0 (broad time/spatial expression) to 1 (specific time/spatial expression). In the gene plots, the x axis shows the samples ordered by stage and organ and the y axis shows expression levels. b, Functional constraints (measured by pLI score) decrease with increasing time- and tissue-specificity (n = 9,965 genes). **P < 0.01, two-sided Wilcoxon rank-sum test. c, Tissue- and time-specificity of mouse genes identified as lethal, subviable, or viable (n = 2,686; two-sided Wilcoxon rank-sum test). d, Levels of functional constraint as measured by RVIS, shet and pLI scores for the human orthologues of genes identified as lethal, subviable and viable in mouse (n = 2,408; two-sided Wilcoxon rank-sum test). e, Tissue- and time-specificity of genes with different developmental trajectories in human (top) and the same after excluding housekeeping genes (bottom). The P values refer to early versus late comparisons, two-sided Wilcoxon rank-sum test. Box plots are as in Fig. 3e.