Evolution of Bcl-2 homology (BH) motifs – homology versus homoplasy

Aouacheria, Abdel; de Laval, Valentine Rech; Combet, Christophe; Hardwick, J. Marie

Bcl-2 family proteins regulate apoptosis in animals. This protein family includes several homologous proteins and a collection of other proteins lacking sequence similarity except for a BH3 motif. Thus, membership in the Bcl-2 family requires only one of the four BH (Bcl-2 homology) motifs. On this basis, a growing number of diverse BH3-only proteins are being reported. While compelling cell biological and biophysical evidence validates many BH3-only proteins, claims about significant BH3 sequence similarity are often unfounded. Computational and phylogenetic analyses suggest that only some BH3 motifs arose by divergent evolution from a common ancestor (homology), while others arose by convergent evolution or random coincidence (homoplasy), challenging current assumptions about which proteins constitute the extended Bcl-2 family.