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Evidence for genomic rearrangements mediated by human endogenous retroviruses during primate evolution

Abstract

Human endogenous retroviruses (HERVs), which are remnants of past retroviral infections of the germline cells of our ancestors1, make up as much as 8% of the human genome and may even outnumber genes2,3. Most HERVs seem to have entered the genome between 10 and 50 million years ago, and they comprise over 200 distinct groups and subgroups1,4. Although repeated sequence elements such as HERVs have the potential to lead to chromosomal rearrangement through homologous recombination between distant loci, evidence for the generality of this process is lacking. To gain insight into the expansion of these elements in the genome during the course of primate evolution, we have identified 23 new members of the HERV-K (HML-2) group, which is thought to contain the most recently active members. Here we show, by phylogenetic and sequence analysis, that at least 16% of these elements have undergone apparent rearrangements that may have resulted in large-scale deletions, duplications and chromosome reshuffling during the evolution of the human genome.

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Figure 1: Example of the synthesis and integration of a HERV-K provirus into a repetitive element.
Figure 2: Neighbor-joining tree containing the 5′ and 3′ LTRs of all full-length HERV-K elements identified in the human genome sequence.

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Acknowledgements

We thank N. Rosenberg for helpful advice. This work was supported by research grants R35 CA 44385 and R01 CA 89441 from the National Cancer Institute. J.M.C. was a Research Professor of the American Cancer Society and J.F.H. was supported in part by training grant CA5441 from the National Cancer Institute.

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Correspondence to John M. Coffin.

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Hughes, J., Coffin, J. Evidence for genomic rearrangements mediated by human endogenous retroviruses during primate evolution. Nat Genet 29, 487–489 (2001). https://doi.org/10.1038/ng775

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