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MBE Advance Access originally published online on August 10, 2005
Molecular Biology and Evolution 2005 22(12):2395-2416; doi:10.1093/molbev/msi234
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Published by Oxford University Press 2005.

Research Article

Phylogenomics of Life-Or-Death Switches in Multicellular Animals: Bcl-2, BH3-Only, and BNip Families of Apoptotic Regulators

Abdel Aouacheria*, Frédéric Brunet{dagger} and Manolo Gouy*

* Laboratoire de Biométrie et Biologie Evolutive, Université Claude Bernard Lyon 1, 69622 Villeurbanne Cedex, France; and {dagger} Laboratoire de Biologie Moléculaire de la Cellule, IFR 128 BioSciences Lyon-Gerland, Lyon Cedex, France

E-mail: aouacher{at}biomserv.univ-lyon1.fr.

In this report, we conducted a comprehensive survey of Bcl-2 family members, a divergent group of proteins that regulate programmed cell death by an evolutionarily conserved mechanism. Using comparative sequence analysis, we found novel sequences in mammals, nonmammalian vertebrates, and in a number of invertebrates. We then asked what conclusions could be drawn from phyletic distribution, intron/exon structures, sequence/structure relationships, and phylogenetic analyses within the updated Bcl-2 family. First, multidomain members having a sequence pattern consistent with the conservation of the Bcl-XL/Bax/Bid topology appear to be restricted to multicellular animals and may share a common ancestry. Next, BNip proteins, which were originally identified based on their ability to bind to E1B 19K/Bcl-2 proteins, form three independent monophyletic branches with different evolutionary history. Lastly, a set of Bcl-2 homology 3–only proteins with unrelated secondary structures seems to have evolved after the origin of Metazoa and exhibits diverse expansion after speciation during vertebrate evolution.

Key Words: comparative genomics • apoptosis • Bcl-2 family • BNips • phylogeny


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