title: Genome-wide analysis of natural selection on human cis-elements.
abstract: BACKGROUND
  It has been speculated that the polymorphisms in the non-coding portion of the human genome underlie much of the phenotypic variability among humans and between humans and other primates. If so, these genomic regions may be undergoing rapid evolutionary change, due in part to natural selection. However, the non-coding region is a heterogeneous mix of functional and non-functional regions. Furthermore, the functional regions are comprised of a variety of different types of elements, each under potentially different selection regimes.
  
  
  CONCLUSIONS
  Using the HapMap and Perlegen polymorphism data that map to a stringent set of putative binding sites in human proximal promoters, we apply the Derived Allele Frequency distribution test of neutrality to provide evidence that many human-specific and primate-specific binding sites are likely evolving under positive selection. We also discuss inherent limitations of publicly available human SNP datasets that complicate the inference of selection pressures. Finally, we show that the genes whose proximal binding sites contain high frequency derived alleles are enriched for positive regulation of protein metabolism and developmental processes. Thus our genome-scale investigation provides evidence for positive selection on putative transcription factor binding sites in human proximal promoters.
authors.affiliation: Department of Genetics, School of Medicine, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Praveen
authors.initials: P
authors.lastname: Sethupathy
authors.forename: Hoa
authors.initials: H
authors.lastname: Giang
authors.forename: Joshua B
authors.initials: JB
authors.lastname: Plotkin
authors.forename: Sridhar
authors.initials: S
authors.lastname: Hannenhalli
mesh_terms: D000483:Alleles; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D017124:Conserved Sequence; D015894:Genome, Human; D006801:Humans; D051379:Mice; D008957:Models, Genetic; D010641:Phenotype; D016012:Poisson Distribution; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic; D013045:Species Specificity
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