Tests for neutrality To gain some insight into a possible positive selection on this locus regarding the level (family and/or intra-family) and the type of selection operating, Ewens-Watterson-Slatkin tests for neutrality [38, 39] GSK3235025 were conducted. Year Sample size Observed

F Expected F p-values         1990 46 0.3535 0.626 0.0201         1991 49 0.3536 0.6302 0.021         1992 43 0.3618 0.6213 0.0317         1993 63 0.3923 0.6463 0.0584         1994 54 0.3957 0.6366 0.0662         1995 51 0.4048 0.633 0.08         1996 68 0.3387 0.651 0.0051         1997 46 0.3573 0.626 0.0253         1998 76 0.3695 0.6575 0.0303         1999 28 0.398 0.5894 0.099         All 524 0.3622 0.7429 0.0108           Size polymorphism Size and sequence polymorphism Year N Observed F Expected F p-value N Observed F Expected F p-value   K1 family 1990 18 this website 0.1728 0.17 0.6612 8 0.1562 0.1562 1 1991 22 0.095 0.099 0.577 11 0.157 0.1542 0.8934 1992 20 0.195 0.1789 0.7793 14 0.0816 0.0816 1 1993 33 0.0964 0.1379 0.0186 20 0.065 0.0607 1 1994 29 0.1249 0.1294 0.551 15 0.0756 0.0756 1 1995 28 0.148 0.1422 0.6971 18 0.1111 0.1113 0.6803 1996 26 0.1775 0.1757 0.6323 18 0.0988 0.1113 0.267 1997 20 0.245 0.1551 0.9901 11 0.0909 0.0909 1 1998 37 0.122 0.1316 0.4808 21 0.1111 0.0962 0.936 1999 14 0.1939 0.2125 0.417 8 0.125 0.125 1 All 247 0.1044 0.0957 0.7197 144 0.0245 0.0214 Dapagliflozin 0.9088

  MAD20 family + Hybrid alleles 1990 18 0.1358 0.1273 0.8024 9 0.1605 0.1683 0.6858 1991 13 0.2071 0.2505 0.2629 8 0.1562 0.1562 1 1992 13 0.1834 0.1698 0.8471 9 0.1111 0.1111 1 1993 18 0.1728 0.1995 0.3267 13 0.1243 0.1208 0.9238 1994 12 0.1667 0.1973 0.2356 9 0.1358 0.1358 1 1995 10 0.32 0.2831 0.9022 9 0.1605 0.1683 0.6858 1996 23 0.2098 0.1906 0.7541 12 0.0972 0.0972 1 1997 16 0.1797 0.1886 0.5808 11 0.1736 0.1885 0.5419 1998 18 0.2037 0.2369 0.3518 10 0.14 0.1455 0.7227 1999 4 0.25 0.25 1 NA NA NA NA All 145 0.1177 0.1201 0.5816 90 0.0365 0.0407 0.2691   RO33 family 1990 NA NA NA NA 10 0.66 0.4919 1 1991 NA NA NA NA 13 0.7396 0.7035 0.6469 1992 NA NA NA NA 10 0.68 0.6826 0.6047 1993 NA NA NA NA 12 0.8472 0.6975 1 1994 NA NA NA NA 13 0.3609 0.3976 0.3849 1995 NA NA NA NA 12 0.7222 0.6975 0.6347 1996 NA NA NA NA 18 NA NA NA 1997 NA NA NA NA 9 0.