Ancient adaptive evolution of the primate antiviral DNA-editing enzyme APOBEC3G.
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.
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Sara L
SL
Sawyer
Michael
M
Emerman
Harmit S
HS
Malik
D000071478:APOBEC Deaminases; D000071479:APOBEC-1 Deaminase; D000071480:APOBEC-3G Deaminase; D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000821:virology; D000818:Animals; D005075:Biological Evolution; D002384:Catalysis; D003564:Cytidine Deaminase / Q000235:genetics; D004247:DNA / Q000235:genetics*; D017931:DNA Primers / Q000737:chemistry; D004251:DNA Transposable Elements; D030541:Databases, Genetic; D019143:Evolution, Molecular; D016346:Gene Products, vif / Q000235:genetics; D005814:Genes, Viral; D015894:Genome, Human; D006678:HIV / Q000235:genetics*; D015658:HIV Infections / Q000235:genetics / Q000821:virology; D006801:Humans; D016013:Likelihood Functions; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics; D009154:Mutation; D009700:Nucleoside Deaminases / Q000235:genetics*; D002679:Pan troglodytes; D010802:Phylogeny; D011110:Polymorphism, Genetic; D017434:Protein Structure, Tertiary; D017393:RNA Editing; D012097:Repressor Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013997:Time Factors; D014779:Virus Replication; D054320:vif Gene Products, Human Immunodeficiency Virus
D017931:DNA Primers; D004251:DNA Transposable Elements; D016346:Gene Products, vif; D009124:Muscle Proteins; D012097:Repressor Proteins; D054320:vif Gene Products, Human Immunodeficiency Virus; D004247:DNA; D009700:Nucleoside Deaminases; D000071479:APOBEC-1 Deaminase; C000605089:APOBEC1 protein, human; D000071478:APOBEC Deaminases; D000071480:APOBEC-3G Deaminase; C120388:APOBEC2 protein, human; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase