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MBE Advance Access published online on July 14, 2004
Molecular Biology and Evolution, doi:10.1093/molbev/msh206
Molecular Biology and Evolution © Society for Molecular Biology and Evolution 2004; all rights reserved
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Accepted June 2, 2004

Original Articles

Evidence of Selection on the Domesticated ERVWE1 env Retroviral Element Involved in Placentation

Bertrand Bonnaud 1, Olivier Bouton 1, Guy Oriol 1, Valérie Cheynet 1, Laurent Duret 2, François Mallet 1*

1 UMR 2714 CNRS-bioMérieux, IFR128 BioSciences Lyon-Gerland, Ecole Normale Supérieure de Lyon, Lyon, France
2 Laboratoire de Biométrie et Biologie Evolutive, UMR CNRS 5558, Université Claude Bernard - Lyon 1, Lyon, France

* To whom correspondence should be addressed. E-mail: francois.mallet{at}ens-lyon.fr.


  Abstract

The human HERV-W multicopy family includes a unique proviral locus, termed ERVWE1, which contains gag and pol pseudogenes and has retained a full-length envelope ORF. This Env protein (syncytin) is a highly fusogenic membrane glycoprotein and has been proposed to be involved in hominoid placental physiology. In order to track the hallmarks of natural selection acting on the ERVWE1 env gene, the pattern of substitutions and indels was analyzed within all human HERV-W elements and along the ERVWE1 orthologous loci in chimpanzee, gorilla, orangutan and gibbon. The comparison of ERVWE1 and paralogous HERV-W copies revealed an ERVWE1 specific signature consisting of a 4 amino-acids deletion in the intracytoplasmic tail of the glycoprotein. We show that this deletion is crucial for the envelope fusogenic activity. The comparison of the human ERVWE1 locus with its orthologs demonstrates the existence of a selective pressure to maintain the env reading frame open. Notably, the 3' part of the env gene, encoding regions required for the fusion process, is under purifying selection. The identification of selective constraints on env ERVWE1 confirms that this retroviral locus has been recruited in the hominoid lineage to become a bona fide gene.

Keywords: HERV-W; paralogous gene; orthologous gene; envelope; endogenous retrovirus; hominoid.
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