Genome-wide analysis of natural selection on human cis-elements
Praveen Sethupathy1, Hoa Giang, Joshua B Plotkin
1Department of Genetics, School of Medicine, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Plos One
|September 11, 2008
Summary
Human genome evolution shows positive selection on transcription factor binding sites in proximal promoters. This suggests rapid evolutionary changes in non-coding DNA, influencing human traits and development.
Area of Science:
- Genomics
- Evolutionary Biology
- Bioinformatics
Background:
- Non-coding DNA polymorphisms contribute to human phenotypic variability.
- Functional regions within non-coding DNA may evolve rapidly due to natural selection.
- Different functional elements within non-coding DNA face distinct selection pressures.
Purpose of the Study:
- To investigate evidence of positive selection on functional elements in the human genome.
- To analyze transcription factor binding sites in human proximal promoters for evolutionary signals.
- To understand the role of selection in shaping human-specific genomic features.
Main Methods:
- Utilized HapMap and Perlegen polymorphism data.
- Applied the Derived Allele Frequency distribution test of neutrality.
- Focused on stringent sets of putative binding sites in human proximal promoters.
Main Results:
- Evidence suggests many human-specific and primate-specific binding sites evolve under positive selection.
- Identified limitations in publicly available human single nucleotide polymorphism (SNP) datasets for inferring selection.
- Genes with high-frequency derived alleles in proximal binding sites are enriched for positive regulation of protein metabolism and development.
Conclusions:
- Genome-scale investigation provides evidence for positive selection on putative transcription factor binding sites in human proximal promoters.
- Positive selection on these binding sites may contribute to human evolutionary adaptations.
- Findings highlight the importance of studying non-coding DNA evolution for understanding human diversity.
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