Antiretroelement activity of APOBEC3H was lost twice in recent human evolution.

Publication Type:

Journal Article

Source:

Cell host & microbe, Volume 4, Issue 3, p.249-59 (2008)

Keywords:

2008, African Continental Ancestry Group, Amino Acid Sequence, Aminohydrolases, Animals, Anti-Retroviral Agents, Antibody Development Core Facility, Basic Sciences Division, Cell Line, Center-Authored Paper, Cytosine Deaminase, Evolution, Molecular, Flow Cytometry Core Facility, Gene Frequency, Genomics Core Facility, HIV, Hominidae, Human Biology Division, Humans, Long Interspersed Nucleotide Elements, Molecular Sequence Data, Mutation, Scientific Imaging Core Facility, Sequence Alignment, Shared Resources, Virus Replication

Abstract:

The primate APOBEC3 gene locus encodes a family of proteins (APOBEC3A-H) with various antiviral and antiretroelement activities. Here, we trace the evolution of APOBEC3H activity in hominoids to identify a human-specific loss of APOBEC3H antiviral activity. Reconstruction of the predicted ancestral human APOBEC3H protein shows that human ancestors encoded a stable form of this protein with potent antiviral activity. Subsequently, the antiviral activity of APOBEC3H was lost via two polymorphisms that are each independently sufficient to destabilize the protein. Nonetheless, an APOBEC3H allele that encodes a stably expressed protein is still maintained at high frequency, primarily in African populations. This stable APOBEC3H protein has potent activity against retroviruses and retrotransposons, including HIV and LINE-1 elements. The surprising finding that APOBEC3H antiviral activity has been lost in the majority of humans may have important consequences for our susceptibility to retroviral infections as well as ongoing retroelement proliferation in the human genome.