The Psoriasis-Associated Deletion of Late Cornified Envelope Genes LCE3B and LCE3C Has Been Maintained Under Balancing Selection Since Human-Denisovan Divergence
**Petar Pajic**, Yen-Lung Lin, Duo Xu, Omer Gokcumen
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.
