Haldane's rule applies to the vast majority of heterogametic organisms examined. These include both male heterogametic (XY or X0-type sex determination, such as found in mammals and Drosophila) and female heterogametic (ZW-type sex determination, such as found in birds and Lepidoptera) animals, and some dioecious plants such as Silene. It appears to be a general pattern associated with heterogamety.
Hybrid sterility and inviability increase reproductive isolation, which leads to speciation. The fact that evolution can produce such a similar pattern of isolation in a vast array of different organisms is striking. However, the actual mechanisms leading to this result in divergent taxa appear to vary. The basis by which the heterogametic sex becomes more susceptible to hybrid inferiority (sterility or inviability) has been a focus of theoretical and empirical explorations that have greatly enriched our understanding of sexual reproduction and speciation.
Many different hypotheses have been advanced to address the genetic basis for hybrid inferiority in the heterogametic sex. Currently, the most popular explanation for Haldane's rule is the composite hypothesis, which divides Haldane's rule into multiple subdivisions, including sterility, inviability, male heterogamety, and female heterogamety. The composite hypothesis states that Haldane's rule in different subdivisions has different causes. Individual genetic mechanisms may not be mutually exclusive, and these mechanisms may act together to cause Haldane's rule in any given subdivision. In contrast to these views that emphasise genetic mechanisms, another view hypothesizes that population dynamics during population divergence may cause Haldane's rule. The following are the main genetic hypotheses.
- Dominance: Homogametic hybrids are only affected by deleterious sex-linked alleles involved in breeding incompatibilities if those alleles are dominant, because they carry another allele that can compensate for recessive mutations. However, heterogametic hybrids, which carry only a single copy of a given sex-linked gene, will be affected by mutations regardless of dominance. Thus, sex-linked incompatibility between diverging populations is more likely to be displayed in the heterogametic sex than homogametic sex. Similarly, the effects of negative X-linked alleles in humans are visible more often in men than women, such as color blindness or hemophilia.
- The "faster male": Male genes are thought to evolve faster due to sexual selection. As a result, male sterility becomes more evident in male heterogametic taxa (XY sex determination). This hypothesis conflicts with Haldane's rule in male homogametic taxa, in which females are more affected by hybrid inferiority. It therefore only applies to male sterility in taxa with XY sex determination, according to the composite theory.
- Meiotic drive: In hybrid populations, selfish genetic elements inactivate sperm cells (i.e.: an X-linked drive factor inactivates a Y-bearing sperm and vice versa).
- The "faster X": Genes on sex chromosomes may evolve more quickly than autosomal genes, causing a larger effect in reproductive isolation.
- Differential selection: Hybrid incompatibilities affecting the heterogametic sex and homogametic sex are fundamentally different isolating mechanisms, which makes heterogametic inferiority (sterility/inviability) more visible or preserved in nature.
Data from multiple phylogenetic groups support a combination of dominance and faster X-chromosome theories. However, it has recently been argued that dominance theory can not explain Haldane's rule in marsupials since both sexes experience the same incompatibilities due to paternal X-inactivation in females.
The dominance hypothesis is the core of the composite theory, and X-linked recessive/dominance effects have been demonstrated in many cases to cause hybrid incompatibilities. There is also supporting evidence for the faster male and meiotic drive hypotheses. For example, a significant reduction of male-driven gene flow is observed in Asian elephants, suggesting faster evolution of male traits.
Although the rule was initially stated in context of diploid organisms with chromosomal sex determination, it has recently been argued that it can be extended to certain species lacking chromosomal sex determination, such as haplodiploids.
There are notable exceptions to Haldane's rule, where the homogametic sex turns out to be inviable while the heterogametic sex is viable and fertile. This has been most commonly noted in Drosophila, where it is proposed to function through maternal effect genes and their interaction with species-specific heterochromatin.
- Haldane, J. B. S. (1922). "Sex ratio and unisexual sterility in hybrid animals". J. Genet. 12: 101–109. doi:10.1007/BF02983075.
- Brothers, Amanda N.; Delph, Lynda F. (2010). "Haldane's rule is extended to plants with sex chromosomes". Evolution 64 (12): 3643–3648. doi:10.1111/j.1558-5646.2010.01095.x.
- Orr, H. A. (1993). "Haldane's rule has multiple genetic causes". Nature 361 (6412): 532–533. doi:10.1038/361532a0. PMID 8429905.
- Wu, C.-I.; Davis, A. W. (1993). "Evolution of postmating reproductive isolation: the composite nature of Haldane's rule and its genetic bases". The American Naturalist 142 (22): 187–212. doi:10.1086/285534. JSTOR 2462812. PMID 19425975.
- Wang, R. (2003). "Differential strength of sex-biased hybrid inferiority in impeding gene flow may be a cause of Haldane's rule". Journal of Evolutionary Biology 16 (2): 353–361. doi:10.1046/j.1420-9101.2003.00528. PMID 14635874.
- Charlesworth, B.; Coyne, J. A.; Barton, N. H. (1987). "The relative rates of evolution of sex chromosomes and autosomes". The American Naturalist 130 (1): 113–146.
- Schilthuizen,, M.; Giesbers, M. C.; Beukeboom, L. W. (2011). "Haldane's rule in the 21st century". Heredity 107 (2): 95–102. doi:10.1038/hdy.2010.170.
- Watson, E.; Demuth, J. (2012). "Haldane's rule in marsupials: what happens when both sexes are functionally hemizygous?". Journal of Heredity 103 (3): 453–458. doi:10.1093/jhered/esr154. PMID 22378959.
- Fickel, J.; Lieckfeldt, D.; Ratanakorn, P.; Pitra, C. (2007). "Distribution of haplotypes and microsatellite alleles among Asian elephants (Elephas maximus) in Thailand". European Journal of Wildlife Research 53 (4): 298–303. doi:10.1007/s10344-007-0099-x. Retrieved 14 April 2008.
- Koevoets, T.; Beukeboom, L. W. (2009). "Genetics of postzygotic isolation and Haldane's rule in haplodiploids". Heredity 102 (1): 16–23. doi:10.1038/hdy.2008.44. PMID 18523445. Retrieved 4 November 2009.
- Sawamura, K. (1996). "Maternal effect as a cause of exceptions for Haldane's rule". Genetics 143 (1): 609–611. PMC 1207293. PMID 8722809.
- Ferree, Patrick M.; Barbash, Daniel A. (2009). "Species-Specific Heterochromatin Prevents Mitotic Chromosome Segregation to Cause Hybrid Lethality in Drosophila". In Noor, Mohamed A. F. PLOS Biology 7 (10): e1000234. doi:10.1371/journal.pbio.1000234. PMC 2760206. PMID 19859525. Retrieved 4 November 2009.
- Coyne, J.A. (1985). "The genetic basis of Haldane's rule". Nature 314 (6013): 736–738. Retrieved 26 January 2007.
- Forsdyke, Donald (2005). "Haldane's rule". Retrieved 11 October 2006.
- Naisbit, Russell E.; Jiggins, Chris D.; Linares, Mauricio; Salazar, Camilo; Mallet, James (2002). "Hybrid Sterility, Haldane's Rule and Speciation in Heliconius cydno and H. melpomene.". Genetics 161 (4): 1517–1526. PMC 1462209. PMID 12196397.