##  [Haldane's Rule](/haldanes-rule-0) 

 Definition

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

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

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

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

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

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

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

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

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.