MBE Advance Access originally published online on August 27, 2009
Molecular Biology and Evolution 2009 26(12):2755-2764; doi:10.1093/molbev/msp190
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Research Articles |
Targets of Balancing Selection in the Human Genome
,1
* Department of Molecular Biology and Genetics, Cornell University
Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD
Department of Human Genetics, University of Chicago
Department of Biological Statistics and Computational Biology, Cornell University
|| Celera Diagnostics, Alameda, CA
¶ Department of Integrative Biology, University of California, Berkeley
# Department of Statistics, University of California, Berkeley
E-mail: andresa{at}mail.nih.gov.
Accepted for publication August 20, 2009.
Balancing selection is potentially an important biological force for maintaining advantageous genetic diversity in populations, including variation that is responsible for long-term adaptation to the environment. By serving as a means to maintain genetic variation, it may be particularly relevant to maintaining phenotypic variation in natural populations. Nevertheless, its prevalence and specific targets in the human genome remain largely unknown. We have analyzed the patterns of diversity and divergence of 13,400 genes in two human populations using an unbiased single-nucleotide polymorphism data set, a genome-wide approach, and a method that incorporates demography in neutrality tests. We identified an unbiased catalog of genes with signatures of long-term balancing selection, which includes immunity genes as well as genes encoding keratins and membrane channels; the catalog also shows enrichment in functional categories involved in cellular structure. Patterns are mostly concordant in the two populations, with a small fraction of genes showing population-specific signatures of selection. Power considerations indicate that our findings represent a subset of all targets in the genome, suggesting that although balancing selection may not have an obvious impact on a large proportion of human genes, it is a key force affecting the evolution of a number of genes in humans.
Key Words: overdominance • frequency-dependent selection • heterosis • human evolution • population genetics • human diversity
1 Present address: Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD.