Haldane's Rule: Genetic Bases and Their Empirical Support

There are few patterns in evolution that are as rigidly held as Haldane's rule (HR), which states, "When in the first generation between hybrids between 2 species, 1 sex is absent, rare, or sterile, that sex is always the heterogametic sex." Yet despite considerable attention for almost a century, questions persist as to how many independent examples exist and what is (are) the underlying genetic cause(s). Here, we review recent evidence extending HR to plants, where previously it has only been documented in animals. We also discuss recent comparative analyses that show much more variation in sex-chromosome composition than previously recognized, thus increasing the number of potential independent origins of HR dramatically. Finally, we review the standing of genetic theories proposed to explain HR in light of the new examples and new molecular understanding.