Antiretroelement activity of APOBEC3H was lost twice in recent human evolution

Cell Host Microbe. 2008 Sep 11;4(3):249-59. doi: 10.1016/j.chom.2008.07.005.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • African Continental Ancestry Group / genetics
  • Amino Acid Sequence
  • Aminohydrolases
  • Animals
  • Anti-Retroviral Agents / metabolism*
  • Cell Line
  • Cytosine Deaminase / chemistry
  • Cytosine Deaminase / genetics*
  • Cytosine Deaminase / metabolism*
  • Evolution, Molecular*
  • Gene Frequency
  • HIV / physiology
  • Hominidae / genetics
  • Hominidae / metabolism
  • Humans
  • Long Interspersed Nucleotide Elements
  • Molecular Sequence Data
  • Mutation
  • Sequence Alignment
  • Virus Replication

Substances

  • Anti-Retroviral Agents
  • APOBEC3H protein, human
  • Aminohydrolases
  • Cytosine Deaminase

Associated data

  • GENBANK/EU861357
  • GENBANK/EU861358
  • GENBANK/EU861359
  • GENBANK/EU861360
  • GENBANK/EU861361