A Model-Based Approach for Identifying Signatures of Ancient Balancing Selection in Genetic Data

Michael DeGiorgio, Kirk E. Lohmueller, Rasmus Nielsen

Research output: Contribution to journalArticle

64 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere1004561
JournalPLoS genetics
Volume10
Issue number8
DOIs
StatePublished - Aug 21 2014

Fingerprint

segregation distortion
Human Genome
methodology
loci
genome
Meiosis
meiosis
Genes
gene
apoptosis
demographic statistics
genes
Alleles
Demography
Apoptosis
alleles
allele
fitness
method
testing

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

DeGiorgio, Michael ; Lohmueller, Kirk E. ; Nielsen, Rasmus. / A Model-Based Approach for Identifying Signatures of Ancient Balancing Selection in Genetic Data. In: PLoS genetics. 2014 ; Vol. 10, No. 8.
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A Model-Based Approach for Identifying Signatures of Ancient Balancing Selection in Genetic Data. / DeGiorgio, Michael; Lohmueller, Kirk E.; Nielsen, Rasmus.

In: PLoS genetics, Vol. 10, No. 8, e1004561, 21.08.2014.

Research output: Contribution to journalArticle

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