A model-based approach for identifying signatures of ancient balancing selection in genetic data

While much effort has focused on detecting positive and negative directional selection in the human genome, relatively little work has been devoted to balancing selection. This lack of attention is likely due to the paucity of sophisticated methods for identifying sites under balancing selection. He...

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Bibliographic Details
Published in:PLoS genetics 2014-08, Vol.10 (8), p.e1004561-e1004561
Main Authors: DeGiorgio, Michael, Lohmueller, Kirk E, Nielsen, Rasmus
Format: Article
Language:English
Subjects:
Alleles
Apoptosis
Biology and Life Sciences
Cannibalism
Colleges & universities
Demography
DNA-Binding Proteins - genetics
Economic models
Evolution
Fitness (Genetics)
Genealogy
Genetic research
Genetics, Population
Genome, Human
Genomes
Genomic Imprinting
HLA-A Antigens - genetics
Human genome
Humans
Male
Meiosis - genetics
Models, Theoretical
Phylogeny
Polymorphism
Population
Population Density
Scholarships & fellowships
Selection, Genetic
Signatures
Statistics
Transcription Factors - genetics
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Summary:While much effort has focused on detecting positive and negative directional selection in the human genome, relatively little work has been devoted to balancing selection. This lack of attention is likely due to the paucity of sophisticated methods for identifying sites under balancing selection. Here we develop two composite likelihood ratio tests for detecting balancing selection. Using simulations, we show that these methods outperform competing methods under a variety of assumptions and demographic models. We apply the new methods to whole-genome human data, and find a number of previously-identified loci with strong evidence of balancing selection, including several HLA genes. Additionally, we find evidence for many novel candidates, the strongest of which is FANK1, an imprinted gene that suppresses apoptosis, is expressed during meiosis in males, and displays marginal signs of segregation distortion. We hypothesize that balancing selection acts on this locus to stabilize the segregation distortion and negative fitness effects of the distorter allele. Thus, our methods are able to reproduce many previously-hypothesized signals of balancing selection, as well as discover novel interesting candidates.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1004561