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Unisexual hybrid disruption can be accounted for by interactions between sex ratio distorters which have diverged in the species of the hybrid cross. One class of unisexual hybrid disruption is described by Haldane's rule, namely that the sex which is absent, inviable or sterile is the heterogametic sex. This effect is mainly due to incompatibility between X and Y chromosomes. We propose that this incompatibility is due to a mutual imbalance between meiotic drive genes, which are more likely to evolve on sex chromosomes than autosomes. The incidences of taxa with sex chromosome drive closely matches those where Haldane's rule applies: Aves, Mammalia, Lepidoptera and Diptera. We predict that Haldane's rule is not universal but is correct for taxa with sex chromosome meiotic drive. A second class of hybrid disruption affects the male of the species regardless of which sex is heterogametic. Typically the genes responsible for this form of disruption are cytoplasmic. These instances are accounted for by the release from suppression of cytoplasmic sex ratio distorters when in a novel nuclear cytotype. Due to the exclusively maternal transmission of cytoplasm, cytoplasmic sex ratio distorters cause only female-biased sex ratios. This asymmetry explains why hybrid disruption is limited to the male.

Causes of sex ratio bias may account for unisexual sterility in hybrids: a new explanation of Haldane's rule and related phenomena.