title: Expansion of a novel endogenous retrovirus throughout the pericentromeres of modern humans.
abstract: BACKGROUND
  Approximately 8% of the human genome consists of sequences of retroviral origin, a result of ancestral infections of the germ line over millions of years of evolution. The most recent of these infections is attributed to members of the human endogenous retrovirus type-K (HERV-K) (HML-2) family. We recently reported that a previously undetected, large group of HERV-K (HML-2) proviruses, which are descendants of the ancestral K111 infection, are spread throughout human centromeres.
  
  
  RESULTS
  Studying the genomes of certain cell lines and the DNA of healthy individuals that seemingly lack K111, we discover new HERV-K (HML-2) members hidden in pericentromeres of several human chromosomes. All are related through a common ancestor, termed K222, which is a virus that infected the germ line approximately 25 million years ago. K222 exists as a single copy in the genomes of baboons and high order primates, but not New World monkeys, suggesting that progenitor K222 infected the primate germ line after the split between New and Old World monkeys. K222 exists in modern humans at multiple loci spread across the pericentromeres of nine chromosomes, indicating it was amplified during the evolution of modern humans.
  
  
  CONCLUSIONS
  Copying of K222 may have occurred through recombination of the pericentromeres of different chromosomes during human evolution. Evidence of recombination between K111 and K222 suggests that these retroviral sequences have been templates for frequent cross-over events during the process of centromere recombination in humans.
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases and Programs in Immunology, Cancer Biology, and Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI, 48109, USA. jazahn@med.umich.edu.
authors.forename: Joseph
authors.initials: J
authors.lastname: Zahn
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases and Programs in Immunology, Cancer Biology, and Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI, 48109, USA. mhkaplan@med.umich.edu.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Kaplan
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases and Programs in Immunology, Cancer Biology, and Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI, 48109, USA. sfischee@cin.edu.uy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Fischer
authors.affiliation: Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, 48109, USA. daimh@umich.edu.
authors.forename: Manhong
authors.initials: M
authors.lastname: Dai
authors.affiliation: Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, 48109, USA. mengf@umich.edu.|Department of Psychiatry, University of Michigan, Ann Arbor, MI, 48109, USA. mengf@umich.edu.
authors.forename: Fan
authors.initials: F
authors.lastname: Meng
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases and Programs in Immunology, Cancer Biology, and Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI, 48109, USA. aksaha@med.umich.edu.
authors.forename: Anjan Kumar
authors.initials: AK
authors.lastname: Saha
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases and Programs in Immunology, Cancer Biology, and Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI, 48109, USA. pcervant@umich.edu.
authors.forename: Patrick
authors.initials: P
authors.lastname: Cervantes
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases and Programs in Immunology, Cancer Biology, and Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI, 48109, USA. susanac@umich.edu.
authors.forename: Susana M
authors.initials: SM
authors.lastname: Chan
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases and Programs in Immunology, Cancer Biology, and Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI, 48109, USA. ddube@usj.edu.
authors.forename: Derek
authors.initials: D
authors.lastname: Dube
authors.affiliation: Departments of Computational Medicine and Bioinformatics, Internal Medicine, and Human Genetics, and School of Public Health, University of Michigan, Ann Arbor, MI, 48109, USA. gomenn@med.umich.edu.
authors.forename: Gilbert S
authors.initials: GS
authors.lastname: Omenn
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases and Programs in Immunology, Cancer Biology, and Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI, 48109, USA. dmarkov@med.umich.edu.|Department of Internal Medicine, Division of Infectious Diseases, University of Michigan, Ann Arbor, MI, 48109-5640, USA. dmarkov@med.umich.edu.
authors.forename: David M
authors.initials: DM
authors.lastname: Markovitz
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases and Programs in Immunology, Cancer Biology, and Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI, 48109, USA. rafaelc@med.umich.edu.|Department of Internal Medicine, Division of Infectious Diseases, University of Michigan, Ann Arbor, MI, 48109-5640, USA. rafaelc@med.umich.edu.
authors.forename: Rafael
authors.initials: R
authors.lastname: Contreras-Galindo
mesh_terms: D001483:Base Sequence; D002503:Centromere / Q000235:genetics / Q000821:virology*; D002877:Chromosomes, Human / Q000235:genetics / Q000821:virology; D019295:Computational Biology; D017931:DNA Primers; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification*; D020077:Endogenous Retroviruses / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D019143:Evolution, Molecular; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
chemical_list: D017931:DNA Primers; D004279:DNA, Viral