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Journal Article
Research Support, Non-U.S. Gov't
The psoriasis-associated deletion of late cornified envelope genes LCE3B and LCE3C has been maintained under balancing selection since Human Denisovan divergence.
BMC Evolutionary Biology 2016 December 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.
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.
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