Three independent insertions of retrovirus-like sequences in the haptoglobin gene cluster of primates.

The human haptoglobin two-gene cluster (HP-HPR) contains two retrovirus-like elements. One (RTVL-Ia) is in the first intron of the HPR gene, and the second (RTVL-Ic) is at the 3'-end of the gene cluster. The chimpanzee three-gene cluster (HP-HPR-HPP) contains an additional, third copy (RTVL-Ib) in the intergenic region between HPR and HPP. RTVL-Ia and RTVL-Ib are essentially full size and have the general structure, 5'-LTR-gag-pol-env-3'-LTR, while RTVL-Ic lacks about one-third of its 5'-part. Although none of the elements has retained long open reading frames, we could detect stretches having amino acids identical to various parts of Moloney murine leukemia virus (Mo-MuLV) proteins. We conclude that the RTVL-I elements were derived from a virus very similar in structure to Mo-MuLV. The DNA sequences surrounding the insertion points of the three RTVL-I elements are not alike and allow the inference that they integrated into the haptoglobin gene cluster independently at some time after the initial formation of the triplicated gene cluster in primates. Comparison of the nucleotide sequences of the three elements leads to the hypothesis that foreign DNA introduced into the genome can initially accumulate mutations more rapidly than the genomic sequences surrounding it.