Ancient adaptive evolution of the primate antiviral DNA-editing enzyme APOBEC3G.

Bibliographic Collection: 
MOCA Reference, APE
Publication Type: Journal Article
Authors: Sawyer, Sara L; Emerman, Michael; Malik, Harmit S
Year of Publication: 2004
Journal: PLoS Biol
Volume: 2
Issue: 9
Pagination: E275
Date Published: 2004 Sep
Publication Language: eng
ISSN: 1545-7885
Keywords: Acquired Immunodeficiency Syndrome, Animals, Biological Evolution, Catalysis, Cytidine Deaminase, Databases, Genetic, DNA, DNA Primers, DNA Transposable Elements, Evolution, Molecular, Gene Products, vif, Genes, Viral, Genome, Human, HIV, HIV Infections, Humans, Likelihood Functions, Molecular Sequence Data, Muscle Proteins, Mutation, Nucleoside Deaminases, Pan troglodytes, Phylogeny, Polymorphism, Genetic, Protein Structure, Tertiary, Repressor Proteins, RNA Editing, Sequence Analysis, DNA, Time Factors, vif Gene Products, Human Immunodeficiency Virus, Virus Replication

Host genomes have adopted several strategies to curb the proliferation of transposable elements and viruses. A recently discovered novel primate defense against retroviral infection involves a single-stranded DNA-editing enzyme, APOBEC3G, that causes hypermutation of HIV. The HIV-encoded virion infectivity factor (Vif) protein targets APOBEC3G for destruction, setting up a genetic conflict between the APOBEC3G and Vif genes. This kind of conflict leads to rapid fixation of mutations that alter amino acids at the protein-protein interface, referred to as positive selection. We show that the APOBEC3G gene has been subject to strong positive selection throughout the history of primate evolution. Unexpectedly, this selection appears more ancient than, and is likely only partially caused by, modern lentiviruses. Furthermore, five additional APOBEC genes in the human genome appear to be engaged in similar genetic conflicts, displaying some of the highest signals for positive selection in the human genome. Despite being only recently discovered, editing of RNA and DNA may thus represent an ancient form of host defense in primate genomes.

DOI: 10.1371/journal.pbio.0020275
Alternate Journal: PLoS Biol.