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Open Access Highly Accessed Research

Primate-specific evolution of an LDLR enhancer

Qian-fei Wang12, Shyam Prabhakar12, Qianben Wang3, Alan M Moses1, Sumita Chanan1, Myles Brown3, Michael B Eisen1, Jan-Fang Cheng12, Edward M Rubin12* and Dario Boffelli12

  • * Corresponding author: Edward M Rubin EMRubin@lbl.gov

  • † Equal contributors

Author Affiliations

1 Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA

2 US Department of Energy Joint Genome Institute, Walnut Creek, California 94598, USA

3 Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA

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Genome Biology 2006, 7:R68  doi:10.1186/gb-2006-7-8-r68

Published: 2 August 2006

Abstract

Background

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.

Results

In this study we identified an anthropoid primate-specific sequence element that contributed to the regulatory evolution of the low-density lipoprotein receptor. Using a combination of close and distant species genomic sequence comparisons coupled with in vivo and in vitro studies, we found that a functional cholesterol-sensing sequence motif arose and was fixed within a pre-existing enhancer in the common ancestor of anthropoid primates.

Conclusion

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.