Ancient Adaptive Evolution of the Primate Antiviral DNA-editing Enzyme APOBEC3G
Affiliations
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.
Viral infection, APOBEC3 dysregulation, and cancer.
Lehle J, Soleimanpour M, Mokhtari S, Ebrahimi D Front Genet. 2025; 15:1489324.
PMID: 39764440 PMC: 11701051. DOI: 10.3389/fgene.2024.1489324.
Adaptation in human immune cells residing in tissues at the frontline of infections.
Salvador-Martinez I, Murga-Moreno J, Nieto J, Alsinet C, Enard D, Heyn H Nat Commun. 2024; 15(1):10329.
PMID: 39609395 PMC: 11605006. DOI: 10.1038/s41467-024-54603-5.
CRL4-DCAF1 Ubiquitin Ligase Dependent Functions of HIV Viral Protein R and Viral Protein X.
Dobransky A, Root M, Hafner N, Marcum M, Sharifi H Viruses. 2024; 16(8).
PMID: 39205287 PMC: 11360348. DOI: 10.3390/v16081313.
The roles of gene duplications in the dynamics of evolutionary conflicts.
Castellanos M, Wickramasinghe C, Betran E Proc Biol Sci. 2024; 291(2024):20240555.
PMID: 38865605 PMC: 11285756. DOI: 10.1098/rspb.2024.0555.
Lorenzo J, Molla L, Amro E, Ibarra I, Ruf S, Neber C Proc Natl Acad Sci U S A. 2024; 121(17):e2312330121.
PMID: 38625936 PMC: 11047093. DOI: 10.1073/pnas.2312330121.