The prototype endogenous retrovirus HERV-K10 was identified in the human genome by its homology to the exogenous mouse mammary tumour virus. By analysis of a short 244 bp segment of the reverse transcriptase (RT) gene of other HERV-K10-like sequences, it has become clear that these elements represent an extended family consisting of multiple groups (the HML-1 to HML-6 subgroups). Some of these elements are transcriptionally active and contain an intact open reading frame for the RT protein, raising the possibility that this family is still expanding through retrotransposition. To better define the relationship of these endogenous retroviruses, we identified ten new members of the HML-2 subgroup. PCR was used to amplify reverse-transcribed RNA of a 595 bp region of the RT gene in a variety of human cell samples, including normal and leukaemic bone marrow and peripheral blood, placenta cells and a transformed T cell line. We provide an extensive phylogenetic analysis of the relationships for this cluster of HERV-K-related endogenous retroviral elements. Nucleotide diversity values for nonsynonymous versus synonymous codon positions indicate that moderately strong selection is or was operating on these retroviral RT gene segments. The evolution of this class of endogenous retroelements is discussed.


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