PT  - JOURNAL ARTICLE
AU  - João C. Teixeira
AU  - Cesare de Filippo
AU  - Antje Weihmann
AU  - Juan R. Meneu
AU  - Fernando Racimo
AU  - Michael Dannemann
AU  - Birgit Nickel
AU  - Anne Fischer
AU  - Michel Halbwax
AU  - Claudine Andre
AU  - Rebeca Atencia
AU  - Matthias Meyer
AU  - Genís Parra
AU  - Svante Pääbo
AU  - Aida M. Andrés
TI  - Long-term balancing selection in <em>LAD1</em> maintains a missense trans-species polymorphism in humans, chimpanzees and bonobos
AID  - 10.1101/006684
DP  - 2014 Jan 01
TA  - bioRxiv
PG  - 006684
4099  - http://biorxiv.org/content/early/2014/11/10/006684.short
4100  - http://biorxiv.org/content/early/2014/11/10/006684.full
AB  - 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 million years of independent evolution. While the majority of these trSNPs were found in three genes of the MHC 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.