TY - JOUR T1 - Hybrid incompatibility caused by an epiallele JF - bioRxiv DO - 10.1101/099317 SP - 099317 AU - Todd Blevins AU - Jing Wang AU - David Pflieger AU - Frédéric Pontvianne AU - Craig S. Pikaard Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/01/09/099317.abstract N2 - Hybrid incompatibility resulting from deleterious gene combinations is thought to be an important step towards reproductive isolation and speciation. Here we demonstrate involvement of a silent epiallele in hybrid incompatibility. In Arabidopsis thaliana strain Col-0, one of the two copies of a duplicated histidine biosynthesis gene, HISN6B is not expressed, for reasons that have been unclear, making its paralog, HISN6A essential. By contrast, in strain Cvi-0, HISN6B is essential because HISN6A is mutated. As a result of these differences, Cvi-0 × Col-0 hybrid progeny that are homozygous for both Col-0 HISN6B and Cvi-0 HISN6A do not survive. We show that HISN6B is not a defective pseudogene in the Col-0 strain, but a stably silenced epiallele. Mutating HISTONE DEACETYLASE 6 (HDA6) or the cytosine methyltransferase genes, MET1 or CMT3 erases HISN6B’s silent locus identity in Col-0, reanimating the gene such that hisn6a lethality and hybrid incompatibility are circumvented. These results show that HISN6-dependent hybrid lethality is a revertible epigenetic phenomenon and provide additional evidence that epigenetic variation has the potential to limit gene flow between diverging populations of a species.Significance statement Deleterious mutations in different copies of a duplicated gene pair have the potential to cause hybrid incompatibility between diverging subpopulations, contributing to reproductive isolation and speciation. This study demonstrates a case of epigenetic gene silencing, rather than pseudogene creation by mutation, contributing to a lethal gene combination upon hybridization of two strains of Arabidopsis thaliana. The findings provide direct evidence that naturally occurring epigenetic variation can contribute to incompatible hybrid genotypes, reducing gene flow between strains of the same species. ER -