Phylogenetic relationships and high-order grouping of the bHLH families. A neighbor-joining (NJ) tree showing the evolutionary relationships of the 44 animal bHLH families listed in Table 1 is shown. We used one gene (usually from mouse) per family to construct this tree. Although there are strong theoretical reasons for preferring the unrooted tree, we show a rooted tree because it is easier to display compactly and more clearly represents the relationships at the tip of the branches. This tree is just a representation of an unrooted tree with rooting that should be considered arbitrary. We used the plant bHLH family (R family) as outgroup. For simplicity, we show a tree in which branch lengths are not proportional to distances between sequences. High-order groups [6,8] are shown. Some of these groups (A and E) are monophyletic groups, others (D and F) correspond to only one family, and yet others (B and C) are paraphyletic (the last common ancestor of the different families that constitute the group is also that of bHLHs that do not belong to that group). A subgroup of group A families (the Atonal 'superfamily' ) is also highlighted and is displayed in more detail in Figure 2.