The psoriasis-associated deletion of late cornified envelope genes LCE3B and LCE3C has been maintained under balancing selection since Human Denisovan divergence

Abstract

Background A common, 32kb deletion of LCE3B and LCE3C genes is strongly associated with psoriasis. We recently found that this deletion is ancient, predating Human-Denisovan divergence. However, it was not clear why negative selection has not removed this deletion from the population. Results Here, we show that the haplotype block that harbors the deletion (i) retains high allele frequency among extant and ancient human populations; (ii) harbors unusually high nucleotide variation (π, P < 4.1 × 10−3); (iii) contains an excess of intermediate frequency variants (Tajima’s D, P < 3.9 × 10−3); and (iv) has an unusually long time to coalescence to the most recent common ancestor (TSel, 0.1 quantile). Conclusions Our results are most parsimonious with the scenario where the LCE3BC deletion has evolved under balancing selection in humans. More broadly, this is consistent with the hypothesis that a balance between autoimmunity and natural vaccination through increased exposure to pathogens maintains this deletion in humans. Electronic supplementary material The online version of this article (doi:10.1186/s12862-016-0842-6) contains supplementary material, which is available to authorized users. Keywords: Copy number variation, Genomic structural variants, Atopic dermatitis, HLA, Defensins, Neanderthal, LCE3A, Human evolution