title: A model-based approach for identifying signatures of ancient balancing selection in genetic data.
abstract: 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.
authors.affiliation: Department of Biology, Pennsylvania State University, University Park, Pennsylvania, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: DeGiorgio
authors.affiliation: Department of Ecology and Evolutionary Biology, University of California, Los Angeles, Los Angeles, California, United States of America.
authors.forename: Kirk E
authors.initials: KE
authors.lastname: Lohmueller
authors.affiliation: Department of Integrative Biology, University of California, Berkeley, Berkeley, California, United States of America; Department of Statistics, University of California, Berkeley, Berkeley, California, United States of America; Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Rasmus
authors.initials: R
authors.lastname: Nielsen
mesh_terms: D000483:Alleles; D017209:Apoptosis; D004268:DNA-Binding Proteins / Q000235:genetics*; D003710:Demography; D005828:Genetics, Population; D015894:Genome, Human; D018392:Genomic Imprinting; D015234:HLA-A Antigens / Q000235:genetics; D006801:Humans; D008297:Male; D008540:Meiosis / Q000235:genetics; D008962:Models, Theoretical; D010802:Phylogeny; D011156:Population Density; D012641:Selection, Genetic; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D015234:HLA-A Antigens; D014157:Transcription Factors; C524048:FANK1 protein, human