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

BMC Evol Biol. 2016 Dec 5;16(1):265. doi: 10.1186/s12862-016-0842-6.


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.

Keywords: Atopic dermatitis; Copy number variation; Defensins; Genomic structural variants; HLA; Human evolution; LCE3A; Neanderthal.

MeSH terms

  • Alleles
  • Cornified Envelope Proline-Rich Proteins / genetics*
  • Evolution, Molecular*
  • Gene Deletion*
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Humans
  • Polymorphism, Single Nucleotide
  • Psoriasis / genetics*
  • Sequence Deletion


  • Cornified Envelope Proline-Rich Proteins
  • LCE3B protein, human
  • LCE3C protein, human