Genetic consequences of programmed genome rearrangement

Jeramiah J. Smith, Carl Baker, Evan E. Eichler, Chris T. Amemiya

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

The lamprey (Petromyzon marinus) undergoes developmentally programmed genome rearrangements that mediate deletion of∼20% of germline DNA from somatic cells during early embryogenesis. This genomic differentiation of germline and soma is intriguing, because the germline plays a unique biological role wherein it must possess the ability to undergo meiotic recombination and the capacity to differentiate into every cell type. These evolutionarily indispensable functions set the germline at odds with somatic tissues, because factors that promote recombination and pluripotency can potentially disrupt genome integrity or specification of cell fate when misexpressed in somatic cell lineages (e.g., in oncogenesis). Here, we describe the development of new genomic and transcriptomic resources for lamprey and use these to identify hundreds of genes that are targeted for programmed deletion from somatic cell lineages. Transcriptome sequencing and targeted validation studies further confirm that somatically deleted genes function both in adult (meiotic) germline and in the development of primordial germ cells during embryogenesis. Inferred functional information from deleted regions indicates that developmentally programmed rearrangement serves as a (perhaps ancient) biological strategy to ensure segregation of pluripotency functions to the germline, effectively eliminating the potential for somatic misexpression.

Original languageEnglish
Pages (from-to)1524-1529
Number of pages6
JournalCurrent Biology
Volume22
Issue number16
DOIs
StatePublished - Aug 21 2012

Bibliographical note

Funding Information:
We thank M. Bronner and T. Sauka-Spengler for access to their lamprey husbandry facilities at the California Institute of Technology. We also thank M.C. Yao for his valuable discussions regarding programmed genome rearrangement. This work was supported by the National Institutes of Health (grant numbers GM079492, GM090049, and RR014085) and the National Science Foundation (grant number MCB-0719558) to C.T.A., the National Institutes of Health (grant numbers T32-HG00035, F32-GM087919) to J.J.S., and the National Institutes of Health (grant number GM58815) to E.E.E. E.E.E. is an Investigator of the Howard Hughes Medical Institute and on the scientific advisory boards for Pacific Biosciences, Inc., SynapDx Corp, and DNAnexus, Inc. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of NIH. Dissection of tissues was performed at Benaroya Research Institute under IACUC protocol 06AM01. Requests for reagents should be addressed to J.J.S. ( jjsmit3@uky.edu ) or C.T.A. ( camemiya@benaroyaresearch.org ).

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (all)
  • Agricultural and Biological Sciences (all)

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