Using a pericentromeric interspersed repeat to recapitulate the phylogeny and expansion of human centromeric segmental duplications.

TitleUsing a pericentromeric interspersed repeat to recapitulate the phylogeny and expansion of human centromeric segmental duplications.
Publication TypeJournal Article
Year of Publication2003
AuthorsHorvath, JE, Gulden, CL, Bailey, JA, Yohn, C, McPherson, JD, Prescott, A, Roe, BA, de Jong, PJ, Ventura, M, Misceo, D, Archidiacono, N, Zhao, S, Schwartz, S, Rocchi, M, Eichler, EE
JournalMol Biol Evol
Date Published2003 Sep
KeywordsAnimals, Centromere, Chromosomes, Human, Evolution, Molecular, Gene Duplication, Genetic Variation, Genome, Human, Hominidae, Humans, In Situ Hybridization, Fluorescence, Molecular Sequence Data, Phylogeny, Physical Chromosome Mapping, Primates, Repetitive Sequences, Nucleic Acid

Despite considerable advances in sequencing of the human genome over the past few years, the organization and evolution of human pericentromeric regions have been difficult to resolve. This is due, in part, to the presence of large, complex blocks of duplicated genomic sequence at the boundary between centromeric satellite and unique euchromatic DNA. Here, we report the identification and characterization of an approximately 49-kb repeat sequence that exists in more than 40 copies within the human genome. This repeat is specific to highly duplicated pericentromeric regions with multiple copies distributed in an interspersed fashion among a subset of human chromosomes. Using this interspersed repeat (termed PIR4) as a marker of pericentromeric DNA, we recovered and sequence-tagged 3 Mb of pericentromeric DNA from a variety of human chromosomes as well as nonhuman primate genomes. A global evolutionary reconstruction of the dispersal of PIR4 sequence and analysis of flanking sequence supports a model in which pericentromeric duplications initiated before the separation of the great ape species (>12 MYA). Further, analyses of this duplication and associated flanking duplications narrow the major burst of pericentromeric duplication activity to a time just before the divergence of the African great ape and human species (5 to 7 MYA). These recent duplication exchange events substantially restructured the pericentromeric regions of hominoid chromosomes and created an architecture where large blocks of sequence are shared among nonhomologous chromosomes. This report provides the first global view of the series of historical events that have reshaped human pericentromeric regions over recent evolutionary time.

Alternate JournalMol Biol Evol
PubMed ID12777517
Grant ListGM58815 / GM / NIGMS NIH HHS / United States
HG002385 / HG / NHGRI NIH HHS / United States
GM08613 / GM / NIGMS NIH HHS / United States
CA094816 / CA / NCI NIH HHS / United States
T32 GM007250 / GM / NIGMS NIH HHS / United States
HG02152 / HG / NHGRI NIH HHS / United States
E.0962 / TI_ / Telethon / Italy

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