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The psoriasis-associated deletion of late cornified envelope genes LCE3B and LCE3C has been maintained under balancing selection since Human Deniso... - PubMed - NCBI
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BMC Evol Biol. 2016 Dec 5;16(1):265.

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

Author information

1
Department of Biological Sciences, University at Buffalo, Cooke 639, Buffalo, NY, 14260, USA.
2
Department of Biological Sciences, University at Buffalo, Cooke 639, Buffalo, NY, 14260, USA. omergokc@buffalo.edu.

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.

KEYWORDS:

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

PMID:
27919236
PMCID:
PMC5139038
DOI:
10.1186/s12862-016-0842-6
[Indexed for MEDLINE]
Free PMC Article
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