Hybrid incompatibility

Hybrid incompatibility is a phenomenon in plants and animals, wherein most offspring produced by the mating of two different species are not viable or are unable to reproduce. Examples of hybrids include mules and ligers from the animal world, and subspecies of the Asian rice crop Oryza sativa from the plant world. Recent research suggests that the source of this incompatibility is largely genetic, as combinations of genes and alleles prove lethal to the hybrid organism.^[1] Incompatibility is not solely influenced by genetics, however, and can be affected by environmental factors such as microbes.^[2] The genetic underpinnings of hybrid incompatibility may provide insight into factors responsible for evolutionary divergence between species.^[3]

Background

Hybrid incompatibility occurs when the offspring of two closely related species are not viable or suffer from infertility. Charles Darwin distinguished hybrid incompatibility from evolution, stating that the the phenomenon is a outcome of the hybridizing species diverging genetically, rather than something that is directly acted upon by natural selection.^[4] The underlying causes of the incompatibility can be varied: earlier research focused on the effects of chromosomal rearrangements and, more typically in plants, changes in ploidy; more recent research has taken advantage of improved molecular techniques and has focused on the effects of genes and alleles in the hybrid and its parents.

Dobzhansky-Muller model

The first major breakthrough in the genetic basis of hybrid incompatibility is the Dobzhansky-Muller model, a combination of findings by Theodosius Dobzhansky and Joseph Muller between 1937 and 1942. By hypothesizing that the incompatibility arose from alterations at two or more loci, rather than one, the incompatible alleles are in one hybrid individual for the first time rather than throughout the population - thus, hybrids that are infertile can develop while the parent populations remain viable.^[5,6] In this way, hybrid infertility contributes in some part to speciation by ensuring that gene flow between diverging species remains limited. Further analysis of the issue has supported this model, although it does not include conspecific interactions, which more recent research has suggested also plays a role.^[4]

Gene identification

Decades after the research of Dobzhansky and Muller, the specifics of hybrid incompatibility were explored by Jerry Coyne, H. Allen Orr, and later Chung-I Wu, who expanded on Coyne and Orr's work. Using introgression techniques to analyze the fertility if Drosophila hybrid and non-hybrid offspring, specific genes that contribute to sterility were identified; one study found that the hybrids of two Drosophila species were made sterile by the interaction of around 100 genes.^[7] These studies widened the scope of the Dobzhansky-Muller model, who thought it likely that more than two genes would be responsible. The ubiquity of Drosophila as a model organism has allowed many of the sterility genes to be sequenced in the years since Wu's study.

Modern directions

With modern molecular techniques, researchers have been able to more accurately identify the underlying genetic causes of hybrid incompatibility. This has led to both the development of the Dobzhansky-Muller model as well as some of its shortcomings being addressed. Recent research has also explored the possibility of external influences on sterility as well.

The "snowball effect"

An extension of the Dobzhansky-Muller model is the "snowball effect"; an accumulation of incompatible loci due to increased species divergence. Since the model posits that sterility is due to negative allelic interaction between the hybridizing species, as species become more diverged it follows that more negative interactions should develop. The snowball effect states that the number of these incompatibilities will increase exponentially over the time of divergence, particularly when more than two loci contribute to the incompatibility. This concept has been exhibited in tests with the flowering plant genus Solanum, with the findings supporting the genetic underpinnings of Dobzhansky-Muller:

"Overall, our results indicate that the accumulation of sterility loci follows a different trajectory from the accumulation of loci for other quantitative species differences, consistent with the unique genetic basis expected to underpin species reproductive isolating barriers. ...In doing so, we uncover direct empirical support for the Dobzhansky-Muller model of hybrid incompatibility, and the snowball prediction in particular." ^[8]

Environmental influences

Though the primary causes of hybrid incompatibility appear to be genetic, external factors may play a role as well. Studies focused primarily on model plants have found that the viability of hybrids can be dependent on environmental influence. Several studies on rice and Arabidopsis species identify temperature as an important factor in hybrid viability; generally, low temperatures seem to cause negative hybrid symptoms to be expressed while high temperatures suppress them, although one rice study found the opposite to be true.^{[9],[10],[11]} There has also been evidence in an Arabidopsis species that in poor environmental conditions (in this case, high temperatures), hybrids did not express negative symptoms and are viable with other populations. When environmental conditions return to normal, however, the negative symptoms are expressed and the hybrids are once again incompatible with other populations.^[12]

Alternatives to Dobzhansky-Muller

Though a multitude of evidence supports the Dobzhansky-Muller model of hybrid sterility and speciation, this does not rule out the possibility that other situations besides the inviable combination of benign genes can lead to hybrid incompatibility. One such situation is incompatibility by way of gene duplication, or the Lynch and Force model (put forth by Michael Lynch and Allan Force in 2000). When gene duplication occurs, there is a possibility that a redundant gene can be rendered non-functional over time by mutations. Given enough inheritance of these genes, a situation may arise in which one sub-population obtains the non-functional gene as its only copy and passes this on to hybrid offspring, rendering the offspring inviable.^[12] This hypothesis is relatively recent compared to Dobzhansky-Muller, but has support as well.

Epialleles

A possible contributor to hybrid incompatibility that fits with the Lynch and Force model better than the Dobzhansky-Muller model is epigenetic inheritance. Epigenetics broadly refers to heritable elements that affect offspring phenotype without adjusting the DNA structure of the offspring. A study found that an Arabidopsis gene is not expressed because it is a silent epiallele, and when this epiallele is inherited by hybrids in combination with a mutant gene at the same locus, the hybrid is inviable.^[1] This fits with the Lynch and Force model because the inheritable epiallele, ordinarily not an issue in non-hybrid populations with non-epiallele copies of the gene, becomes problematic when it is the only copy of the gene in the hybrid population. Given that much research into epigenetics is still ongoing, the concept that epialleles can have a large influence on hybrid incompatibility and, by extension, speciation will likely be further examined.

References:

1. Blevins, T., Wang, J., Pflieger, D., Pontvianne, F., & Pikaard, C. S. (2017). Hybrid incompatibility caused by an epiallele. Proceedings of the National Academy of Sciences, 114(14), 3702-3707. doi:10.1073/pnas.1700368114
2. Chen C, E Z, Lin HX. Evolution and Molecular Control of Hybrid Incompatibility in Plants. Front Plant Sci. 2016;7:1208. Published 2016 Aug 11. doi:10.3389/fpls.2016.01208
3. Maheshwari, S., & Barbash, D. (2011). The Genetics of Hybrid Incompatibilities. Annual Review of Genetics, 45, 331-355.
4. Johnson, N. (2008) Hybrid incompatibility and speciation. Nature Education, 1(1):20
5. Dobzhansky, T. Genetics and the Origin of Species (New York, Columbia University, 1937)
6. Muller, H. J. Isolating mechanisms, evolution, and temperature. Biology Symposium 6, 71–125 (1942)
7. Wu, C. I., et al. Haldane's rule and its legacy: Why are there so many sterile males? Trends in Ecology and Evolution 11, 281–284 (1996)
8. Moyle, L., & Nakazato, T. Hybrid Incompatibility "Snowballs" between Solanum Species. Science, 329(5998), 1521-1523. DOI: 10.1126/science.1193063
9. Bomblies K., Lempe J., Epple P., Warthmann N., Lanz C., Dangl J. L., et al. (2007). Autoimmune response as a mechanism for a Dobzhansky-Muller-type incompatibility syndrome in plants. PLoS Biol. 5:e236 10.1371/journal.pbio.0050236
10. Fu C. Y., Wang F., Sun B. R., Liu W. G., Li J. H., Deng R. F., et al. (2013). Genetic and cytological analysis of a novel type of low temperature-dependent intrasubspecific hybrid weakness in rice. PLoS ONE 8:e73886 10.1371/journal.pone.0073886
11. Chen C., Chen H., Lin Y. S., Shen J. B., Shan J. X., Qi P., et al. (2014). A two-locus interaction causes interspecific hybrid weakness in rice. Nat. Commun. 5:3357 10.1038/ncomms4357
12. Lynch, M., Force, A.G. (2000) The origin of interspecific genomic incompatibility via genome duplication. The American Naturalist. 156:590-605