Genome-wide amplification of proviral sequences reveals new polymorphic HERV-K(HML-2) proviruses in humans and chimpanzees that are absent from genome assemblies.
BACKGROUND
To date, the human population census of proviruses of the Betaretrovirus-like human endogenous retroviral (HERV-K) (HML-2) family has been compiled from a limited number of complete genomes, making it certain that rare polymorphic loci are under-represented and are yet to be described.


RESULTS
Here we describe a suppression PCR-based method called genome-wide amplification of proviral sequences (GAPS) that selectively amplifies DNA fragments containing the termini of HERV-K(HML-2) proviral sequences and their flanking genomic sequences. We analysed the HERV-K(HML-2) proviral content of 101 unrelated humans, 4 common chimpanzees and three centre d'etude du polymorphisme humain (CEPH) pedigrees (44 individuals). The technique isolated HERV-K(HML-2) proviruses that had integrated in the genomes of the great apes throughout their divergence and included evolutionarily young elements still unfixed for presence/absence.


CONCLUSIONS
By examining the HERV-K(HML-2) proviral content of 145 humans we detected a new insertionally polymorphic Type I HERV-K(HML-2) provirus. We also observed provirus versus solo long terminal repeat (LTR) polymorphism within humans at a previously unreported, but ancient, locus. Finally, we report two novel chimpanzee specific proviruses, one of which is dimorphic for a provirus versus solo LTR. Thus GAPS enables the isolation of uncharacterised HERV-K(HML-2) proviral sequences and provides a direct means to assess inter-individual genetic variation associated with HERV-K(HML-2) proviruses.
Department of Genetics, University of Leicester, University Road, Leicester, LE1 7RH, UK. cm182@leicester.ac.uk.
Catriona M
CM
Macfarlane
Department of Genetics, University of Leicester, University Road, Leicester, LE1 7RH, UK. rmb19@leicester.ac.uk.
Richard M
RM
Badge
D000818:Animals; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D020077:Endogenous Retroviruses / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification*; D014644:Genetic Variation; D006801:Humans; D008969:Molecular Sequence Data; D002679:Pan troglodytes; D016133:Polymerase Chain Reaction; D011533:Proviruses / Q000235:genetics*; D012192:Retroviridae Infections / Q000662:veterinary* / Q000821:virology*; D017422:Sequence Analysis, DNA
D004279:DNA, Viral