We describe a 5-to 6-kilobase-pair repetitive family in human DNA. One member of this family is linked to the ,-globin gene cluster and is close to the 3' breakpoints of three different naturally occurring deletions involving this gene cluster. Sequence analysis indicates that this element includes terminal direct repeats of 415 base pairs that exhibit the features of long terminal repeats (LTRs) of retroviruses. A potential histidine tRNA primer binding site occurs just 3' to the 5' direct repeat. This retrovirus-like element interrupts a member of the Kpn I family of repeated DNA and is bracketed by a 5-base-pair directly repeated sequence. When attempts are made to clone the element in bacteriophage, homologous recombination between the LTR-like sequences is very frequently observed. Copy number estimates by two methods indicate that the element is repeated 800-1000 times in the human genome. We term this Homo sapiens family of retroviruslike elements having a histidine tRNA primer binding site the hsRTVL-H family.Endogenous retroviral sequences have been the subject of considerable research over many years (1, 2), and their possible functions have been the cause of much speculation. Retroviral proviruses have been found in the normal DNA of a variety of species, but those found in chickens and mice are by far the best characterized (1, 3). Some endogenous proviruses can produce virus but others, such as the multicopy VL30 elements (4-6) and intracisternal A-type particles (IAPs) (7-11) in mice, have not been shown to produce infectious virions and hence are usually called retrovirus-like elements.There have been many attempts to identify endogenous proviruses in human DNA (12). The approach used most recently to search for such sequences is that of DNA hybridization of known retroviral sequences to normal human DNA. Using this method, several laboratories have detected and cloned human retrovirus-like DNA (13-16). The best characterized of these elements are homologous to Moloney leukemia virus, contain long terminal repeats (LTRs), and are present in multiple copies, some of which are transcribed (17-19).We report here the identification of a different human multicopy endogenous retrovirus-like element. Unlike the sequences previously described, this element was not detected by nucleic acid hybridization to viral probes.
MATERIALS AND METHODSSources. Human DNA was isolated from cultured normal human embryonic fibroblasts (563 from Robert DeMars). The Kpn I family probes, pCa4A-10 and pCa4A-12, represent two halves of a long Kpn I family member and were kindly provided by Maxine Singer.Phage Cloning. The Xba I library was constructed by isolating the 9-to 18-kbp fragments of a complete Xba I digest of human DNA by preparative agarose gel electrophoresis and ligating these fragments into Xba I arms of DNA from X phage Charon 35 (23). The ligated DNA was then packaged in vitro (24). The size-selected HindIII, EcoRI, and Sst I libraries mentioned in the text were constructed by digesting human DNA to c...