Hybrid incompatibility caused by an epiallele

Abstract

Hybrid incompatibility resulting from deleterious gene combinations is thought to be an important step toward reproductive isolation and speciation. Here, we demonstrate involvement of a silent epiallele in hybrid incompatibility. In <i>Arabidopsis thaliana</i> accession Cvi-0, one of the two copies of a duplicated histidine biosynthesis gene, <i>HISN6A</i>, is mutated, making <i>HISN6B</i> essential. In contrast, in accession Col-0, <i>HISN6A</i> is essential because <i>HISN6B</i> is not expressed. Owing to these differences, Cvi-0 × Col-0 hybrid progeny that are homozygous for both Cvi-0 <i>HISN6A</i> and Col-0 <i>HISN6B</i> do not survive. We show that <i>HISN6B</i> of Col-0 is not a defective pseudogene, but a stably silenced epiallele. Mutating <i>HISTONE DEACETYLASE 6</i> (<i>HDA6</i>), or the cytosine methyltransferase genes <i>MET1</i> or <i>CMT3,</i> erases <i>HISN6B's</i> silent locus identity, reanimating the gene to circumvent <i>hisn6a</i> lethality and hybrid incompatibility. These results show that <i>HISN6</i>-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.