Radka Reifová1, S. Lorena Ament-Velásquez2, Yann Bourgeois3, Jenn Coughlan4, Jonna Kulmuni5,6, Agnieszka P. Lipinska7,8, Genta Okude9, Laurie Stevison10, Kohta Yoshida9 and Jun Kitano9 1Department of Zoology, Faculty of Science, Charles University, 128 00 Prague, Czech Republic 2Department of Zoology, Stockholm University, 106 91 Stockholm, Sweden 3DIADE, University of Montpellier, CIRAD, IRD, 34090 Montpellier, France 4Department of Ecology & Evolutionary Biology, Yale University, New Haven, Connecticut 06520, USA 5Institute for Biodiversity and Ecosystem Dynamics, Department of Evolutionary and Population Biology, University of Amsterdam, 1012 Amsterdam, The Netherlands 6Organismal & Evolutionary Biology Research Programme, University of Helsinki, 00100 Helsinki, Finland 7Department of Algal Development and Evolution, Max Planck Institute for Biology, 72076 Tuebingen, Germany 8CNRS, UMR 8227, Integrative Biology of Marine Models, Sorbonne Université, Station Biologique de Roscoff, 29680 Roscoff, France 9Department of Genomics and Evolutionary Biology, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan 10Department of Biological Sciences, Auburn University, Auburn, Alabama 36849, USA Correspondence: radka.reifovanatur.cuni.cz; jkitanonig.ac.jp

Intrinsic postzygotic isolation typically appears as reduced viability or fertility of interspecific hybrids caused by genetic incompatibilities between diverged parental genomes. Dobzhansky–Muller interactions among individual genes, and chromosomal rearrangements causing problems with chromosome synapsis and recombination in meiosis, have both long been considered as major mechanisms behind intrinsic postzygotic isolation. Recent research has, however, suggested that the genetic basis of intrinsic postzygotic isolation can be more complex and involves, for example, overall divergence of the DNA sequence or epigenetic changes. Here, we review the mechanisms of intrinsic postzygotic isolation from genic, chromosomal, genomic, and epigenetic perspectives across diverse taxa. We provide empirical evidence for these mechanisms, discuss their importance in the speciation process, and highlight questions that remain unanswered.