Abstract
Analysis of primate-specific evolution of the LDL receptor enhancer demonstrates a molecular mechanism by which ancestral mammalian regulatory elements can evolve to perform new functions.
Highlights
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
To examine the role of cis-regulatory changes in the emergence of novel physiologic traits in primates, we investigated the evolution of regulatory elements of the low-density lipoprotein (LDL) receptor gene (LDLR), which is a key player in maintaining lipid homeostasis
Because humans and nonhuman primates share many features of cholesterol metabolism, we scanned for elements that are preferentially conserved in primates under the hypothesis that primate-specific regulatory sequences contribute to the distinctive biology of those species
Summary
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. Since King and Wilson's provocative paper was published in 1975 [1], differences in gene regulatory sequences have been predicted to be among the major sources of phenotypic evolution and divergence among animals. Consistent with this hypothesis, cis-regulatory changes have been found to play an important role in the evolution of morphologic features in model organisms [2]. To examine the role of cis-regulatory changes in the emergence of novel physiologic traits in primates, we investigated the evolution of regulatory elements of the low-density lipoprotein (LDL) receptor gene (LDLR), which is a key player in maintaining lipid homeostasis.
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