Haldane’s law works through X:Autosome incompatibility in Caenorhabditis briggsae/C. nigoni hybrids

More than one hundred years ago, JBS Haldane noted that in a cross between two species, if one of the sexes is absent, rare or sterile, the affected sex is heterogametic. The underlying genetic causes for this phenomenon have been a source of debate ever since. Here, we test how Haldane’s rule operates in Caenorhabditis nematodes by studying (1) crosses involving sex-determination mutants of two hybridizing species, and (2) crosses involving tetraploids. Our results indicate that the critical feature underlying Haldane’s rule is incompatibility between a sex chromosome derived from only one species, and autosome pairs derived from both. In addition, we show that the mechanisms for evaluating the X:Autosome ratio have diverged during recent nematode evolution. We conclude that the way interactions between sex chromosomes and autosomes are structured causes them to play an important role in establishing genetic barriers between newly separating species. Haldane’s rule suggests that in hybrid crosses, the heterogametic sex is often rare or sterile. This study crosses Caenorhabditis nematodes, and determines that an underlying feature of Haldane’s rule is incompatibility between a sex chromosome derived from only one species and autosome pairs from both.