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Accelerated Evolution of Conserved Noncoding Sequences in Humans

Shyam Prabhakar,^1,2* James P. Noonan,^1,2* Svante Pääbo,³ Edward M. Rubin^1,2

Changes in gene regulation likely influenced the profound phenotypic divergence of humans from other mammals, but the extent of adaptive substitution in human regulatory sequences remains unknown. We identified 992 conserved noncoding sequences (CNSs) with a significant excess of human-specific substitutions. These accelerated elements were disproportionately found near genes involved in neuronal cell adhesion. To assess the uniqueness of human noncoding evolution, we examined CNSs accelerated in chimpanzee and mouse. Although we observed a similar enrichment near neuronal adhesion genes in chimpanzee, the accelerated CNSs themselves exhibited almost no overlap with those in human, suggesting independent evolution toward different neuronal phenotypes in each species. CNSs accelerated in mouse showed no bias toward neuronal cell adhesion. Our results indicate that widespread cis-regulatory changes in human evolution may have contributed to uniquely human features of brain development and function.

¹ U.S. Department of Energy (DOE) Joint Genome Institute, Walnut Creek, CA 94598, USA.
² Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
³ Max Planck Institute for Evolutionary Anthropology, D-04103 Leipzig, Germany.

^* These authors contributed equally to this work.

To whom correspondence should be addressed. E-mail: emrubin{at}lbl.gov

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