Evolutionary grouping of the transforming growth factor-beta superfamily.

TGF beta 1 is the prototype of a superfamily of differentiation factors with at least 18 distinct members. This classification is based on amino acid homology in the C-terminus of these polypeptides. The rates of amino acid substitution for several family members were estimated from a comparison of homologous sequences derived from different species. These rates were approximately constant for any given protein, but values varied greatly between different groups. This variation is a reflection of the great functional diversity found within the TGF beta superfamily. Maximum parsimony analysis allowed us to classify members of the TGF beta superfamily into five main groups (INH alpha, MIS, TGF beta s, INH beta s and BMPs) and various subgroups. This classification predicts possible phylogenetic relationships among these proteins. In the future, it is hoped that this method of classification will be adopted by all our colleagues, as an aid in deciding whether newly discovered proteins are the product of duplicated or homologous genes. This would suggest proteins with either similar or identical functions.