title: Identification and antiviral activity of common polymorphisms in the APOBEC3 locus in human populations.
abstract: There are seven members of the APOBEC3 family in humans (APOBEC3A through APOBEC3H) that have antiviral activity against retroviruses and/or retroelements. To determine whether variants in APOBEC3 genes in human populations have altered antiviral activity, we identified and functionally tested novel single nucleotide variants (SNVs) in APOBEC3 genes present in the 1000 Genome Project dataset. We found that common variants minor allele frequency (> 1%) of APOBEC3A, C, F, and G do not affect protein function. However, we found that two common novel polymorphisms in APOBEC3D decrease antiviral activity against HIV-1, and one polymorphism decreases activity against Alu retrotransposons. We characterized the diversity of APOBEC3 genes in three human populations and find significant evidence that APOBEC3D has evolved under purifying selection in recent human history. These data suggest that the activity of APOBEC3D has been maintained in human populations for a cellular function in host defense.
authors.affiliation: Molecular and Cellular Biology Program, University of Washington, Seattle, WA, USA.
authors.forename: Nisha K
authors.initials: NK
authors.lastname: Duggal
authors.forename: Wenqing
authors.initials: W
authors.lastname: Fu
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Akey
authors.forename: Michael
authors.initials: M
authors.lastname: Emerman
mesh_terms: D000071478:APOBEC Deaminases; D020087:Alu Elements / Q000187:drug effects / Q000235:genetics; D000998:Antiviral Agents / Q000494:pharmacology*; D003564:Cytidine Deaminase / Q000235:genetics* / Q000494:pharmacology*; D043525:Cytosine Deaminase / Q000235:genetics* / Q000378:metabolism; D019143:Evolution, Molecular; D005787:Gene Frequency; D005828:Genetics, Population; D015894:Genome, Human / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D011110:Polymorphism, Genetic
chemical_list: D000998:Antiviral Agents; D043525:Cytosine Deaminase; D000071478:APOBEC Deaminases; C502889:APOBEC3 proteins, human; C578087:APOBEC3D protein, human; D003564:Cytidine Deaminase
keywords: Alu elements; Apobec3 locus; Apobec3D; Common polymorphisms; HIV; Human evolution