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APOBEC3 GENES ARE UNIQUE TO MAMMALS, BUT COPY NUMBERS VARY SIGNIFICANTLYAPOBEC3 (A3) proteins are of considerable interest because most are potent DNA cytidine deaminases that have the capacity to restrict the replication and/or edit the sequences of a wide variety of parasitic elements, including many retroviruses and retrotransposons (reviewed in references 5, 8-10, and 14). Likely substrates include (i) lentiviruses, such as human immunodeficiency virus type 1, human immunodeficiency virus type 2, simian immunodeficiency virus, maedi-visna virus, feline immunodeficiency virus, and equine infectious anemia virus; (ii) alpha-, beta-, gamma-, and deltaretroviruses, such as Rous sarcoma virus, MasonPfizer monkey virus or mouse mammary tumor virus, murine leukemia virus or feline leukemia virus, and human T-cell leukemia virus or bovine leukemia virus, respectively; (iii) spumaviruses, such as primate foamy virus and feline foamy virus; (iv) hepadnaviruses, such as hepatitis B virus; (v) endogenous retroviruses and long terminal repeat retrotransposons, such as human endogenous retrovirus K, murine intracisternal A particle, murine MusD, and porcine endogenous retrovirus; (vi) non-long terminal repeat retroposons, such as L1 and Alu; and (vii) DNA viruses, such as adenoassociated virus and human papillomavirus. Over the past few years, there has also been an increasing appreciation for the multiple, distinct mechanisms that parasitic elements use to coexist with the A3 proteins of their hosts. Together, these observations indicate that the evolution of the A3 proteins has been driven by a requirement to minimize the spread of exogenous and endogenous genetic threats. The likelihood that the A3 proteins might exist solely for this purpose has been supported recently by studies indicating that A3-deficient mice have no obvious phenotypes apart from a notable increase in susceptibility to retrovirus infection (16,19,21,23).A3 genes are specific to mammals and are organized in a tandem array between two vertebrate-conserved flanking genes, CBX6 and CBX7 (Fig. 1A) (e.g., see reference 13). Based on a limited number of genomic sequences, it is already clear that the A3 copy number can vary greatly from mammal to mammal. For instance, mice have one A3 gene (10, 16), pigs have two (13), cattle and sheep have three (13), cats have four (17), horses have six (2), and humans and chimpanzees have seven (4, 10, 11). Other mammals are likely to have copy numbers within this range, but the cat and horse loci, in particular, highlight the difficulty in making such predictions (2, 17).
