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Trends Cell Biol. 2013 Mar;23(3):103-11. doi: 10.1016/j.tcb.2012.10.010. Epub 2012 Nov 27.

Evolution of Bcl-2 homology motifs: homology versus homoplasy.

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Molecular Biology of the Cell Laboratory, Ecole Normale Supérieure de Lyon, LBMC UMR 5239 CNRS - UCBL - ENS Lyon, 46 Allée d'Italie, 69364 Lyon Cedex 07, France.


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 Bcl-2 homology (BH)3 motif. Thus, membership in the Bcl-2 family requires only one of the four BH motifs. On this basis, a growing number of diverse BH3-only proteins are being reported. Although compelling cell biological and biophysical evidence validates many BH3-only proteins, claims of 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), whereas others arose by convergent evolution or random coincidence (homoplasy), challenging current assumptions about which proteins constitute the extended Bcl-2 family.

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