Haldane's rule represents a remarkable observation in the early stage of speciation. The rule also applies to two species which, after allopatric speciation has occurred, form hybrids when secondary contact in an area of sympatry results in incomplete reproductive isolation. It was formulated in 1922 by the British evolutionary biologist J.B.S. Haldane:
Haldane's rule applies to the vast majority of heterogametic organisms examined. These include both male heterogametic (XY or XO-type sex determination, such as found in mammals and Drosophila) and female heterogametic (ZW-type sex determination, such as found in birds and Lepidoptera), and some dioecious plants such as Silene. It appears to be a general pattern associated with heterogamety.
Hybrid dysfunction (sterility and inviability) is a major form of postzygotic reproductive isolation, which occurs in early stages of 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 remains largely undefined. 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 evolutionary mechanisms to produce Haldane's rule. 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.
- The dominance hypothesis: Heterogametic hybrids are affected by all, recessive or dominant, X-linked alleles causing incompatibilities. However, homogametic hybrids are only affected by dominant deleterious X-linked alleles. Heterogametic hybrids, which carry only a single copy of a given X-linked gene, will be affected by mutations regardless of dominance. Thus, an X-linked incompatibility between diverging populations is more likely to be expressed in the heterogametic sex than homogametic sex.
- 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.
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