An empirical pattern in hybridization and speciation stating that when hybrid inviability or sterility affects only one sex of the offspring of a cross between species, it is most often the heterogametic sex (the sex with two different sex chromosomes).

Principle

Genetic incompatibilities between diverging genomes disproportionately affect the heterogametic sex because recessive incompatibility alleles on sex chromosomes are unmasked in the heterogametic genotype.

Demonstration

Crosses between closely related Drosophila species often yield sterile or inviable male hybrids (XY), consistent with the heterogametic-male pattern in species with male heterogamety.

Misapplication

Asserting Haldane's rule predicts the direction or magnitude of hybrid dysfunction for any particular cross ignores that autosomal incompatibilities, maternal effects, or environmental interactions can produce exceptions.

Consequence

Correctly applied, Haldane's rule focuses attention on sex chromosome evolution and dominance effects in speciation genetics and helps prioritize genetic mapping of incompatibilities.

Reversal

The reversal would be a pattern where the homogametic sex is more frequently sterile or inviable, which can occur under specific genetic architectures or when sex chromosomes are not the main carriers of incompatibilities.

Boundary

Pertains to crosses between diverging taxa and to postzygotic reproductive isolation; it does not assert causes in all taxa and may not apply in systems with nonstandard sex determination or hermaphroditism.

Semantic Tension

Competes with explanations emphasizing faster-male evolution, mitochondrial–nuclear incompatibilities, or asymmetric gene flow; multiple mechanisms can produce similar sex‑biased hybrid dysfunction patterns.

Synthesis

Haldane's rule is a robust empirical regularity in speciation: when hybrid sterility or inviability is sex-biased, the heterogametic sex is most often affected, reflecting the interaction of dominance, sex-chromosome exposure, and broader genomic incompatibilities with notable exceptions.