Haldane's rule

Haldane's rule is an observation about the early stage of speciation, formulated in 1922 by the British evolutionary biologist J. B. S. Haldane, that states that if — in a species hybrid — only one sex is inviable or sterile, that sex is more likely to be the heterogametic sex. The heterogametic sex is the one with two different sex chromosomes; in therian mammals,^[a] for example, this is the male.^[2]

In humans, barring intersex conditions causing aneuploidy and other unusual states, it is the male that is heterogametic, with XY sex chromosomes.

Overview

Haldane himself described the rule as:

When in the F1 offspring of two different animal races one sex is absent, rare, or sterile, that sex is the heterozygous sex (heterogametic sex).^[3]

Haldane's rule applies to the vast majority of species that have heterogametic chromosomal sex determination (e.g. XX females vs. XY males, or ZW females vs. ZZ males).

The rule includes both male heterogametic (XY or XO-type sex determination, such as found in mammals and Drosophila fruit flies) and female heterogametic (ZW or Z0-type sex determination, as found in birds and butterflies), and some dioecious plants such as campions.^[4]

Hybrid dysfunction (sterility and inviability) is a major form of post-zygotic reproductive isolation, which occurs in early stages of speciation. Evolution can produce a similar pattern of isolation in a vast array of different organisms. However, the actual mechanisms leading to Haldane's rule in different taxa remain largely undefined.

Hypotheses

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.^[5]^[6] In contrast to these views that emphasize genetic mechanisms, another view hypothesizes that population dynamics during population divergence may cause Haldane's rule.^[7]

The main genetic hypotheses are:

Dominance: Heterogametic hybrids are affected by all X-linked alleles (be they recessive or dominant) causing incompatibilities due to divergent alleles being brought together. 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 in the homogametic sex.
The "faster male": Male genes are thought to evolve faster due to sexual selection.^[6] 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 hemizygous chromosomes may evolve more quickly by enhancing selection on possible recessive alleles causing a larger effect in reproductive isolation.^[8]
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.^[7]

Data from multiple phylogenetic groups support a combination of dominance and faster X-chromosome theories.^[9] 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.^[10]

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.^[11]

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^[12] and hermaphrodites.^[9]

Exceptions

In some instances, the homogametic sex turns out to be inviable while the heterogametic sex is viable and fertile. This is seen in some Drosophila fruit flies.^[13]^[14]

Notes

^ Unlike other mammals, monotremes have more than two different sex chromosomes. The platypus has five pairs. Short-beaked echidnas have four pairs plus one female-only chromosome.^[1]

References

^ Deakin, J. E.; Graves, J. A. M.; Rens, W. (2012). "The Evolution of Marsupial and Monotreme Chromosomes". Cytogenetic and Genome Research. 137 (2–4): 113–129. doi:10.1159/000339433. hdl:1885/64794. PMID 22777195.
^ Turelli, M.; Orr, H. A. (May 1995). "The dominance theory of Haldane's rule". Genetics. 140 (1): 389–402. doi:10.1093/genetics/140.1.389. PMC 1206564. PMID 7635302.
^ Haldane, J. B. S. (1922). "Sex ratio and unisexual sterility in hybrid animals". J. Genet. 12 (2): 101–109. doi:10.1007/BF02983075. S2CID 32459333.
^ 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. PMID 20681984. S2CID 27145478.
^ Orr, H. A. (1993). "Haldane's rule has multiple genetic causes". Nature. 361 (6412): 532–533. Bibcode:1993Natur.361..532O. doi:10.1038/361532a0. PMID 8429905. S2CID 4304828.
^ ^a ^b 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. Bibcode:1993ANat..142..187D. doi:10.1086/285534. JSTOR 2462812. PMID 19425975. S2CID 35214550.
^ ^a ^b 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.x. PMID 14635874. S2CID 7127922.
^ 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. Bibcode:1987ANat..130..113C. doi:10.1086/284701. JSTOR 2461884. S2CID 84357596.
^ ^a ^b 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. PMC 3178397. PMID 21224879.
^ 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. PMC 3331990. 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. Bibcode:2007EJWR...53..298F. doi:10.1007/s10344-007-0099-x. S2CID 25507884.
^ 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.
^ Sawamura, K. (1996). "Maternal effect as a cause of exceptions for Haldane's rule". Genetics. 143 (1): 609–611. doi:10.1093/genetics/143.1.609. PMC 1207293. PMID 8722809.
^ Ferree, Patrick M.; Barbash, Daniel A. (2009). "Species-specific heterochromatin prevents mitotic chromosome Segregation to Cause hybrid lethality in Drosophila". PLOS Biology. 7 (10): e1000234. doi:10.1371/journal.pbio.1000234. PMC 2760206. PMID 19859525.