title: Recent Selection Changes in Human Genes under Long-Term Balancing Selection.
abstract: Balancing selection is an important evolutionary force that maintains genetic and phenotypic diversity in populations. Most studies in humans have focused on long-standing balancing selection, which persists over long periods of time and is generally shared across populations. But balanced polymorphisms can also promote fast adaptation, especially when the environment changes. To better understand the role of previously balanced alleles in novel adaptations, we analyzed in detail four loci as case examples of this mechanism. These loci show hallmark signatures of long-term balancing selection in African populations, but not in Eurasian populations. The disparity between populations is due to changes in allele frequencies, with intermediate frequency alleles in Africans (likely due to balancing selection) segregating instead at low- or high-derived allele frequency in Eurasia. We explicitly tested the support for different evolutionary models with an approximate Bayesian computation approach and show that the patterns in PKDREJ, SDR39U1, and ZNF473 are best explained by recent changes in selective pressure in certain populations. Specifically, we infer that alleles previously under long-term balancing selection, or alleles linked to them, were recently targeted by positive selection in Eurasian populations. Balancing selection thus likely served as a source of functional alleles that mediated subsequent adaptations to novel environments.
authors.affiliation: Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany cesare_filippo@eva.mpg.de aida.andres@eva.mpg.de.
authors.forename: Cesare
authors.initials: C
authors.lastname: de Filippo
authors.affiliation: Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
authors.forename: Felix M
authors.initials: FM
authors.lastname: Key
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Ghirotto
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Benazzo
authors.affiliation: Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
authors.forename: Juan R
authors.initials: JR
authors.lastname: Meneu
authors.affiliation: Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Weihmann
authors.affiliation: Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
authors.forename: Genís
authors.initials: G
authors.lastname: Parra
authors.affiliation: National Human Genome Research Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Green
authors.affiliation: Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany cesare_filippo@eva.mpg.de aida.andres@eva.mpg.de.
authors.forename: Aida M
authors.initials: AM
authors.lastname: Andrés
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000235:genetics; D000483:Alleles; D005075:Biological Evolution; D004268:DNA-Binding Proteins / Q000235:genetics; D030561:Databases, Nucleic Acid; D019143:Evolution, Molecular; D005787:Gene Frequency; D059647:Gene-Environment Interaction; D014644:Genetic Variation; D005828:Genetics, Population / Q000379:methods*; D006801:Humans; D011956:Receptors, Cell Surface / Q000235:genetics; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA / Q000379:methods
chemical_list: D004268:DNA-Binding Proteins; C484392:PKDREJ protein, human; D011956:Receptors, Cell Surface; C095988:ZNF473 protein, human; D015094:3-Hydroxyacyl CoA Dehydrogenases; C108634:HSD17B10 protein, human
keywords: environmental changes; natural selection; out-of-Africa.
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