Hybrid mutual exclusivity is a term used to describe the observed phenomenon that mating between closely related species produces inviable or infertile offspring with low fitness. These phenomena are evident in a broad range of organisms including plants, animals, and even micro-organisms. Incompatibility shown in interspecies hybridization is believed to be the main cause of post-zygotic reproductive isolation, which is in turn a hallmark of speciation.
These sterility and lethality effects are normally the result of improper genetic interactions that diverging species have in one of the hybridization lineages. This paper aims to analyze the genetics of interspecific hybrid mutual exclusivity in different contexts by identifying the different causes of hybrid mutual exclusivity such as the evolutionary causes of divergence, the mode of development of hybrid mutual exclusivity, and how the degree of mutual exclusivity affects hybrid fitness.
Interspecific hybrid mutual exclusivity is important in species diversification and species maintenance, which are central topics in evolutionary biology. Speciation involves a series of steps in which multiple reproductive barriers accumulate over time, starting from hybridization producing viable progeny, followed by hybrid sterility and inviability, and eventually complete pre-zygotic reproductive isolation. Consequently, understanding the genetic basis of hybrid mutual exclusivity is of great interest for understanding the evolutionary process of speciation.
Previous research has found that the causes leading to post-zygotic reproductive barriers can be at different levels. For example, at the epigenetic level, chromatin binding proteins may not be able to interact with chromosomes from another species in a hybrid, causing gene expression to be misregulated; at the chromosomal level, changes in ploidy number which normally occurs in plant hybrids or differences in chromosome number such as hybrids of horses and donkeys; at the molecular level, negative epistatic interactions of alleles at different genetic loci.
Mode of hybrid mutual exclusivity:
Though interspecies hybrid mutual exclusivity is a reproductive barrier that drives speciation, it faces a serious problem, which is how such maladaptive inviability and sterility could evolve by natural selection. One of the theories seeking to explain how mutual exclusivity between closely related species develops without either of them going through an adaptive valley is the Dobzhansky-Muller Model. It posits that hybrid mutual exclusivity is unlikely to arise from just a single change at one locus due to underdominance (viable AA or aa but inviable Aa) that such hybrid being heterozygotes have lower fitness should an allelic substitution not take place by natural selection.
Even if genetic drift exists, the population needs to be small so the possibility is relatively low. In contrast, Dobzhansky-Muller mutual exclusivities result from negative epistatic interactions between alleles located at least at two loci. These exclusivities causing genes, called ‘complementary genes’, show no harmful effects within either population but dysfunction with genes from other species when brought in hybrid.
The basic theoretical account is that two allopatric populations, starting with a common hereditary genetic background, accumulate genetic changes along their divergence such that allele permutation at different venues occur in the detached populations. The derived alleles are neutral or even beneficial in their own genetic background but incompatible with the later derived alleles at different venues in another population.
Other than the Dobzhansky-Muller Model, there is another rule concerning hybridization – Haldane’s Rule. It states that when one sex in the interspecies hybrid is absent, infertile or rare, that sex is the heterogametic sex. Haldane’s Rule suggests different hypotheses; the most popular one is the dominance hypothesis, proposing a genetic theory similar to sex-linked disorders in humans, such as color blindness and hemophilia.
It proposes that the dominance of mutual exclusiveness alleles plays a role in hybrid fitness, and evidence was found to prove they are on average partly recessive. The hybrid of heterogametic sex carrying only a single sex-linked gene will suffer from the negative effect of the alleles, regardless of dominance. However, a homogametic sex hybrid will suffer only if the mutual exclusiveness allele is dominant because a recessive allele will be covered by another allele in the second X-chromosome.
As a result, disorders are more visible in heterogametic sex hybrids than homogametic ones. Secondly, research data support a faster-X theory, that genes on the X-chromosome evolve much faster than those on somatic chromosomes, which in turn has a greater effect on hybrid mutual exclusiveness. In fact, there are many life examples, such as inviable male hybrids of Drosophila and significant lack of male mules at birth, corroborating the general truth of Haldane’s Law.
Hybrid mutual exclusiveness in plants:
Spontaneous hybridization used to be recognized as an important driving force of speciation as there is evident proof that many plant species have hybrid lineages. New species can arise by hybridization much more easily in plants since the hybrid plants can still reproduce even if they are infertile by different mechanisms of asexual reproduction, such as vegetative extension. However, recent research has found that the occurrence of spontaneous hybridization is not as widespread as previously believed. Instead, the occurrence of spontaneous hybridization is partly restricted to a portion of families and an even smaller proportion of genera.
In practice, the hurtful phenotype of hybrid is frequently due to an autoimmune syndrome called hybrid necrosis. There are several mechanisms underlying hybrid necrosis, but seemingly, they frequently involve the immune system. One illustration of hybrid necrosis is tapetal-specific, causing male sterility which is normally found in hermaphroditic plants. It was found that cytonuclear incompatibility plays a major function in this developmental aberration.
A male-sterile phenotype is observed in the hybrid with tapetal impairment, which raises pollen mother cells. Mitochondrial genes trigger a standard tract of programmed cell death (PCD) which destroys the tapetum, while atomic genes suppress male sterility and restore pollen fertility by a counteracting step.
There are different mitochondrial genotypes triggering cell death in different ways by changing the complex regulatory cascade leading to PCD, while each of them has a specific set of matching atomic genes that block PCD and restore normal function. As a consequence, tapetal development is regulated by the balance of riotous effects of mitochondria and the defensive effect of atomic genes. However, this delicate mitochondrial-nuclear balance is disturbed in hybrids and therefore upsets the regulatory control of programmed cell death, causing tapetal abnormalities and male sterility.
Furthermore, sometimes PCD further affects tissues throughout the plant as PCD is involved in the development of tissues like leaves and xylem. Besides, PCD is a defensive mechanism against pathogens in plant cells, which implies that misregulation of PCD can lead to serious problems of cell death. This type of cytonuclear incompatibility may contribute to the investigation of development, as rapid development of mitochondrial and atomic genes is expected. Hybrids from crosses between Nemophila menziesii and a diverged population show symptoms such as skinny growth, thickened and curled leaves, deviant petals, and anthers with small or no pollen, which match the features of the PCD-induced aberrations.
Another instance of hybrid necrosis was discovered when analyzing the species Arabidopsis thaliana. Crosses between A. thaliana strains show hybrid necrosis, which was found to be a Dobzhansky-Muller-Type Incompatibility Syndrome, affecting a negative epistatic interaction between 2 to 4 venues.
A highly polymorphic NB-LRR gene, which is the most common immune gene in plants, was mapped and found responsible for the improper regulation of the immune system in hybrids. The NB-LRR expression is usually regulated by a trans-acting component encoded at the second venue, which a failure of coevolution of the two interacting venues may upset the balance of the interaction, leading to ectopic activation. Hybrids show a lower threshold for activation of active immune response, and some hybrids may have enhanced resistance against pathogens when compared to their parents.
Typically, mitochondrial genes are matrilineally transmitted only through seeds but not through pollen, while atomic genes are biparentally transmitted. In this instance, hybrid survival is not dependent on the direction of the cross, meaning which species act as the maternal parent, showing it is not caused by deviant nuclear-cytoplasmic interactions like those involved in cytoplasmic male sterility.
This type of hybrid necrosis is experimentally found to be temperature-sensitive, which hybrids suffer from deadliness at their typical habitat temperature, but the autoimmune response is greatly suppressed at a higher temperature. The temperature-dependent effect suggests a quantitative incompatibility, in which the hurtful phenotype is subjected to the dose of the incompatible alleles.
Hybrid mutual exclusiveness in animate beings:
Although a clear illustration of the intercrossed asepsis and inviability remains a black box, a few intercrossed mutual exclusiveness genes were identified with the powerful advanced genetic tools that have been invented, such as mapping mutations, chromosomal duplicates and omissions, and DNA technology.
A “Dobzhansky-Muller” type mutual exclusiveness was identified in a platyfish species. Hybrids between platyfish Xiphophorus maculatus and a related species, the helleri Xiphophorus swordtail, show inviability. Moreover, backcross hybrids of those species frequently develop malignant tumors and eventually die. With the aid of molecular genetic analysis, an X-linked intercrossed mutual exclusiveness gene, Xmrk-2, which codes for a fresh receptor tyrosine kinase, was found to be misexpressed in hybrids, leading to cancer formation.
The Xmrk-2 gene maps as a topographic point-producing gene in platyfish, with a repressor gene locating on a somatic chromosome. The autosomal repressor is missing in hybrids, resulting in improper regulation of Xmrk2 gene expression.
More HI genes were discovered during studies on a frequently used genetic tool, Drosophila. Those identified mutual exclusiveness genes include Odysseus-Homeobox (OdsH), Lethal hybrid rescue (Lhr), Hybrid male rescue (Hmr), and Nup96 genes. Ods causes male asepsis in intercrossed crosses between D. simulans and D. mauritiana, as it encodes a duplicated transcription factor that is misregulated in the testicles of the hybrid.
Research found loss of map mutation of Hmr gene in D. melanogaster and Lhr in D. simulans suppress intercrossed male deadliness. Both genes demonstrate asymmetry in causing intercrossed deadliness, which is stated in the Dobzhansky-Muller model by the effect that omission mutation of those alleles of another species cannot rescue the hybrid.
Among those mutual exclusiveness genes, Nup96 seems to be more enlightening in the present study. The Nup96 gene codes for a protein that stably binds to the nuclear pore complex, which is the largest macromolecular complex in eukaryotes. The Nup96 nucleoporins play structural roles in nuclear pore complex-mediated nucleocytoplasmic trafficking of RNAs and proteins.
In intercrossed crosses between D. melanogaster and D. simulans, a D. simulans Nup96 allele causes deadliness in hemizygous for the D. melanogaster X chromosome but not in hemizygous for the D. simulans X chromosome. The observation fits the Dobzhansky-Muller model postulation that a D. simulans allele of Nup96 would not be incompatible with its venue on its own X chromosome.
The Nup96 protein is found interacting with other nucleoporins, such as Nup75, Nup107, Nup133, Nup160, Seh1, Nup37, and Nup43, to form a Nup 107 subcomplex. Sequencing analyses of polymorphism of those genes suggest a trend of adaptive coevolution between Nup96 and some of its interacting proteins.
Such coevolution events may provide a new model different from the assumption of population genetics that permutation takes place independently. Comparing with the independent permutations model, non-independent development may speed up divergence of intercrossed mutual exclusiveness, since permutations at 1-locus increase the probability of permutations at interacting venues within a lineage.
Such coevolution event may supply a new theoretical account different from the premise of population familial that permutation take topographic point independently. Comparing with independent permutations theoretical account, non-independent development may rush up divergency of intercrossed mutual exclusivenesss since permutations at 1-locus addition the chance of permutations at interacting venue within a line of descent.
Besides, Coevolution of interacting cistrons may concentrate permutations in one line of descent which imply a addition in possibility of derived-ancestral allelomorphs intercrossed mutual exclusivenesss, opposing to the postulation of Dobzhansky-Muller Model.
A consequence of mutual exclusiveness on birthrate and viability:
A past experiment investigated whether intercrossed mutual exclusiveness affect asepsis and deadliness otherwise utilizing two yeast species S. cerevisiae and S. paradoxs. Fertility and viability of the barm were measured by the monogenesis frequence and the clonal growing rate severally. The heterozygous F1 loanblends were non used in the trial as recessionary mutual exclusiveness may be masked. Alternatively, homozygous F2 loanblends formed by autodiploidization of the F1 gamete were examined. Result show that for each F2 person, the growth-based was much higher than sporulation-based fittingness, bespeaking intercrossed asepsis is more marked than intercrossed viability. A possible molecular mechanisms is that a S. cerevisiae atomic cistron MRS1 was found incompatible with a S. paradoxs mitochondrial cistron COX1. This cytonuclear mutual exclusiveness disturbs cellular metamorphosis on non-fermentable medium where barm sporulates and hence cause intercrossed asepsis. Furthermore, meiosis-related cistrons was found fast germinating in the barm which is a possible account for the observation that fertility-related mutual exclusivenesss are more common than viability-related mutual exclusivenesss.
A past experiment investigated whether intercrossed mutual exclusivity affects asepsis and deadliness by utilizing two yeast species, S. cerevisiae and S. paradoxus. Fertility and viability of the yeast were measured by the monogenesis frequency and the clonal growth rate, respectively. The heterozygous F1 hybrids were not used in the trial as recessive mutual exclusivity may be masked. Alternatively, homozygous F2 hybrids formed by autodiploidization of the F1 gamete were examined.
Results show that for each F2 individual, the growth-based fitness was much higher than sporulation-based fitness, indicating intercrossed asepsis is more marked than intercrossed viability. A possible molecular mechanism is that an S. cerevisiae nuclear gene, MRS1, was found incompatible with an S. paradoxus mitochondrial gene, COX1. This cytonuclear mutual exclusivity disturbs cellular metabolism on non-fermentable medium where yeast sporulates and hence causes intercrossed asepsis.
Furthermore, meiosis-related genes were found fast germinating in the yeast, which is a possible explanation for the observation that fertility-related mutual exclusivities are more common than viability-related mutual exclusivities.
Interspecific intercrossed mutual exclusivity is one of the causes of reproductive isolation between species, which is a defining characteristic of the biological concept of species. Knowing the genetic basis of intercrossed mutual exclusivity is therefore a significant process of detecting the beginning of speciation. As genetic impetus and selection continues after speciation, the split species continue to diverge, and the strength of mutual exclusivity will only keep on increasing.
Therefore, finding a mutual exclusivity gene does not necessarily mean finding a speciation gene. As a result, speciation genes should be defined as evolved to cause mutual exclusivity only at the time of speciation, but it poses a great difficulty to isolate a speciation gene after speciation has taken place over millions of years. However, hints about the phylogenetic relation among species may be obtained by observing the exclusivity pattern of intercrossed crosses from different related species.
For example, a Nup96-dependent deadliness shown in intercrossed between D. melanogaster-D. simulans and D. melanogaster-D. sechellia, but not in D. melanogaster-D. mauritiana intercrossed, suggesting D. mauritiana may have speciated before D. simulans and D. sechellia. Apart from this, more evolutionary events could be predicted with the incidents that all non-synonymous permutations of Nup96 allele of D. simulans are also found in D. mauritiana, which indicate Nup96 allele may have diverged prior to the divergence of D. simulans and D. mauritiana. Besides, a gene locating on the X chromosome incompatible with Nup96 alleles to cause deadliness should have diverged on the D. melanogaster lineage due to the occurrence of deadliness only on hybrids with the D. melanogaster X chromosome, neither with D. simulans nor D. sechellia.
Evolutionary forces that drive the divergence of speciation genes
In addition to the identity and characteristics of speciation genes, life scientists are also interested in understanding the driving force behind the divergence of speciation genes. Increasing evidence shows that intercrossed mutual exclusivity genes evolve as a byproduct of adaptive development and are rapidly evolving.
For example, through gene function and DNA sequencing, the Nup96 gene was found to have diverged among Drosophila species with a significant excess of non-synonymous permutations ratio to synonymous permutations, indicating that the Nup96 allelomorph is under positive natural selection instead of familial impetus. Additionally, new hypotheses propose that intragenomic struggle may play a role in which meiotic thrust may contribute to the development of postmating generative isolation.
Past research has suggested that the independent segregation of Mendelian rules may not be as universal as believed, but, in fact, non-Mendelian segregation is masked in the population because suppressor mutations are rapidly fixed after a distorter arises. A autosomal repressor allelomorph of sex-ratio deformation was found to be associated with intercrossed asepsis in Drosophila hybrids.
In order to understand speciation, we must first know the source of generative isolation. Although the majority of the truth about intercrossed mutual exclusivity remains uncertain, it provides insight for us to examine the evolutionary divergence among species. With the efforts of scientists and the invention of new technology, a more realistic and detailed explanation about the familial of intercrossed mutual exclusivity can be constructed, bringing us closer to the process of speciation.