Hybrid incompatibility caused by an epiallele

Proc Natl Acad Sci U S A. 2017 Apr 4;114(14):3702-3707. doi: 10.1073/pnas.1700368114. Epub 2017 Mar 7.


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 Arabidopsis thaliana accession Cvi-0, one of the two copies of a duplicated histidine biosynthesis gene, HISN6A, is mutated, making HISN6B essential. In contrast, in accession Col-0, HISN6A is essential because HISN6B is not expressed. Owing to these differences, Cvi-0 × Col-0 hybrid progeny that are homozygous for both Cvi-0 HISN6A and Col-0 HISN6B do not survive. We show that HISN6B of Col-0 is not a defective pseudogene, but a stably silenced epiallele. Mutating HISTONE DEACETYLASE 6 (HDA6), or the cytosine methyltransferase genes MET1 or CMT3, erases HISN6B's silent locus identity, reanimating the gene to circumvent hisn6a lethality and hybrid incompatibility. 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.

Keywords: DNA methylation; epigenetic inheritance; gene silencing; histone deacetylation; hybrid incompatibility.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Arabidopsis / genetics
  • Arabidopsis / physiology*
  • Arabidopsis Proteins / genetics*
  • Chimera
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA-Cytosine Methylases / genetics
  • Epigenesis, Genetic*
  • Gene Expression Regulation, Plant
  • Gene Silencing
  • Genes, Lethal
  • Histone Deacetylase 6 / genetics
  • Mutation
  • Transaminases / genetics*


  • Arabidopsis Proteins
  • DNA-Cytosine Methylases
  • MET1 protein, Arabidopsis
  • CMT3 protein, Arabidopsis
  • DNA (Cytosine-5-)-Methyltransferases
  • Transaminases
  • HISN6B protein, Arabidopsis
  • HPA1 protein, Arabidopsis
  • Histone Deacetylase 6