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

Authors
  • Sawyer, Sara L1
  • Emerman, Michael
  • Malik, Harmit S
  • 1 Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Type
Published Article
Journal
PLoS Biology
Publisher
Public Library of Science
Publication Date
Sep 01, 2004
Volume
2
Issue
9
Identifiers
PMID: 15269786
Source
Medline
Language
English
License
Unknown

Abstract

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.

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