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Open Access Publications from the University of California

Primate-Specific Evolution of an LDLR Enhancer

  • Author(s): Wang, Qian-fei
  • Prabhakar, Shyam
  • Wang, Qianben
  • Moses, Alan M.
  • Chanan, Sumita
  • Brown, Myles
  • Eisen, Michael B.
  • Cheng, Jan-Fang
  • Rubin, Edward M.
  • Boffelli, Dario
  • et al.
Abstract

Sequence changes in regulatory regions have often been invoked to explain phenotypic divergence among species, but molecular examples of this have been difficult to obtain. In this study, we identified an anthropoid primate specific sequence element that contributed to the regulatory evolution of the LDL receptor. Using a combination of close and distant species genomic sequence comparisons coupled with in vivo and in vitro studies, we show that a functional cholesterol-sensing sequence motif arose and was fixed within a pre-existing enhancer in the common ancestor of anthropoid primates. Our study demonstrates one molecular mechanism by which ancestral mammalian regulatory elements can evolve to perform new functions in the primate lineage leading to human.

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