Cell invasion, sexual development, transcription factors and CCCH zinc fingers have less constrained protein coding regions than the other groups of genes considered. Elements of the heatmap represent the p-values resulting from testing the alternative hypothesis that proteins in a particular group rank among the least constrained proteins (higher dN/dS) among all proteins with orthologs in 2 particular species. The 15 groups were ranked from the least constrained to the most constrained in each of the 5 cross-species comparisons and the sum of the ranks was determined (Table S2) and used to order the protein groups in the heatmap. Pf-Pv, Pf-Pk, Pf-Py, Pf-Pb and Pf-Pc represent results from comparisons between P. falciparum and P. vivax, P. knowlesi, P. yoelii, P. berghei and P. chabaudii respectively.