title: Long-Term Balancing Selection in LAD1 Maintains a Missense Trans-Species Polymorphism in Humans, Chimpanzees, and Bonobos.
abstract: Balancing selection maintains advantageous genetic and phenotypic diversity in populations. When selection acts for long evolutionary periods selected polymorphisms may survive species splits and segregate in present-day populations of different species. Here, we investigate the role of long-term balancing selection in the evolution of protein-coding sequences in the Homo-Pan clade. We sequenced the exome of 20 humans, 20 chimpanzees, and 20 bonobos and detected eight coding trans-species polymorphisms (trSNPs) that are shared among the three species and have segregated for approximately 14 My of independent evolution. Although the majority of these trSNPs were found in three genes of the major histocompatibility locus cluster, we also uncovered one coding trSNP (rs12088790) in the gene LAD1. All these trSNPs show clustering of sequences by allele rather than by species and also exhibit other signatures of long-term balancing selection, such as segregating at intermediate frequency and lying in a locus with high genetic diversity. Here, we focus on the trSNP in LAD1, a gene that encodes for Ladinin-1, a collagenous anchoring filament protein of basement membrane that is responsible for maintaining cohesion at the dermal-epidermal junction; the gene is also an autoantigen responsible for linear IgA disease. This trSNP results in a missense change (Leucine257Proline) and, besides altering the protein sequence, is associated with changes in gene expression of LAD1.
authors.affiliation: Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
authors.forename: João C
authors.initials: JC
authors.lastname: Teixeira
authors.affiliation: Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
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: Antje
authors.initials: A
authors.lastname: Weihmann
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 Integrative Biology, University of California, Berkeley.
authors.forename: Fernando
authors.initials: F
authors.lastname: Racimo
authors.affiliation: Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Dannemann
authors.affiliation: Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Nickel
authors.affiliation: International Center for Insect Physiology and Ecology, Nairobi, Kenya.
authors.forename: Anne
authors.initials: A
authors.lastname: Fischer
authors.affiliation: Clinique vétérinaire du Dr. Jacquemin, Maisons-Alfort, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Halbwax
authors.affiliation: Lola Ya Bonobo sanctuary, Kinshasa, Democratic Republic Congo.
authors.forename: Claudine
authors.initials: C
authors.lastname: Andre
authors.affiliation: Réserve Naturelle Sanctuaire à Chimpanzés de Tchimpounga, Jane Goodall Institute, Pointe-Noire, Republic of Congo.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Atencia
authors.affiliation: Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Meyer
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: Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
authors.forename: Svante
authors.initials: S
authors.lastname: Pääbo
authors.affiliation: Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany aida_andres@eva.mpg.de.
authors.forename: Aida M
authors.initials: AM
authors.lastname: Andrés
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000235:genetics*; D019143:Evolution, Molecular; D059472:Exome / Q000235:genetics; D014644:Genetic Variation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D024041:Non-Fibrillar Collagens / Q000235:genetics*; D019974:Pan paniscus; D002679:Pan troglodytes; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic; D000097805:Collagen Type XVII
chemical_list: D001324:Autoantigens; D024041:Non-Fibrillar Collagens; D000097805:Collagen Type XVII
keywords: LAD1; balancing selection; great apes; trans-species polymorphism