Biologists have long suspected that the origin of species can be a result of differential evolution and adaptation between populations. Yet generalities about the phenotypes or underlying genes responsible for speciation remain broadly unresolved. Despite this uncertainty, the disproportionate role of sex chromosomes in speciation is well recognized. Two routes of investigation into speciation have been important in implicating the sex chromosomes in speciation. First, classic studies crossing individuals in the lab have disproportionately implicated the heterogametic sex and, then, the X chromosome specifically, in post-zygotic hybrid failure. Second, studies of gene flow across landscapes have similarly identified the X by showing disproportionate divergence in allele frequencies between populations. Studies directly measuring gene flow between parapatric species at zones of contact and, then, studies inferring rates of introgression, both indicate reduced gene exchange between populations on the X compared to the rest of the genome. Ideally, studying why the sex chromosomes play a disproportionate role in speciation will provide insights to some of the other unresolved questions in the study of the origin of species.
The first signs of a role for sex chromosomes in hybrid failures arose from investigations of sex-ratio distortion in hybrid offspring. In response to a debate on the cause of sex-biased broods from hybrid crosses, JBS Haldane undertook a review of hybrid infertility and inviability in species with sex chromosomes. Haldane famously found that, regardless of sex determination system, “when in the F1 offspring of two different animal races one sex is absent, rare, or sterile, that sex is the heterozygous sex”. As was common of his time, Haldane thought the pattern could be due to structural rearrangements between the sex chromosomes. Hybrids between populations where different rearrangements between X and Y, or between X and autosomes, had fixed would cause hybrids to be missing genes, and therefore be inviable, when they inherited the respective chromosome from each parent from which genes moved. This model has recently received renewed interest, but is probably unable to entirely account for the generality of Haldane’s rule. Haldane’s rule was the first empirical finding to implicate sex chromosomes in speciation.
In the 1930s, Dobzhansky and Muller independently proposed an alternate model of the evolution of reproductive isolation to chromosomal rearrangements, which instead involved epistasis (it has also been pointed out that this idea was proposed by Bateman thirty years earlier). Under the Dobzhansky-Muller Incompatibility (DMI) model, two alternate alleles at two different loci fix in isolated populations. Neither change has a deleterious effect on fitness within each population, but when brought together in the same genome, these alternatively fixed alleles have strong detrimental epistatic effects. The deleterious epistatic effects of these incompatibilities cause hybrids to fail and thereby keep populations reproductively isolated. Using the DMI model, Muller proposed that, given new mutations were most often recessive, Haldane’s rule could be explained through inviability by epistasis: unmasking recessive incompatibilities on the X by a degenerate Y, known as hemizygosity, would cause the heterogametic sex to fail more often than the homogametic sex. This ‘dominance hypothesis’ was formally developed by A. Orr and M. Turelli in the 1990s (the recessivity of incompatibilities can also account for hybrid failure in later generations, see below). Generally, the uncovering of recessive deleterious or incompatible alleles on the X by a degenerate Y is thought to play an important role in Haldane’s rule. The dominance hypothesis for Haldane’s rule and the DMI model more broadly have had a large and important impact on the study of speciation.
While investigating the genetic basis of Haldane’s rule, Dobzhansky discovered that the role of the sex chromosomes in hybrid failure extended beyond Haldane’s rule. In 1930s crossing experiments, Dobzhansky showed that the X chromosome played a disproportionate role in hybrid breakdown that could not be explained by recessive incompatibilities alone. The results from Dobzhansky’s work were rediscovered 50 years later and led to a slew of insightful crossing experiments which showed the role for the sex chromosomes was much more complex than F1 dominance effects. Most conclusively, work by J.P. Masley and D. Presgraves in hybrids of Drosophila mauritiana and D. sechellia found a higher density of genes with negative effects on introgression on the X, even while controlling for hemizygosity. These studies revealed a second rule of speciation: the X plays a disproportionate role in speciation compared to the rest of the genome. This observation has also been confirmed in several other systems, including plants. The ‘large-X effect’, as it has come to be known, suggests the role of the sex chromosomes extends beyond a simple unmasking of recessive DM incompatibilities.
One simple way of accounting for the large X effect again assumes a degenerate Y chromosome. If adaptive mutations are most often recessive, hemizygosity would increase the rate of evolution on the X by revealing recessive adaptive mutations. This higher rate of adaptive evolution on the X can increase the likelihood of incompatible mutations on X chromosomes compared to elsewhere in the genome. The “faster X” model has been expanded to include the unique effective population size of the sex chromosomes and, in theory, can explain asymmetries in post-mating isolation. This faster-X model would suggest the sex chromosomes are involved in speciation only because the Y chromosome is degenerate.
Empirical investigation into the faster-X found evidence that genes on the X evolve fast, but this pattern is not always associated with hemizygosity. The evidence supports a faster-X effect on coding sequence evolution in several Drosophila lineages, spiders, mice and tentative in Silene, and on gene expression in Drosophila. Hemizygosity of the Z enhances purifying selection but not positive selection in Satyrine butterflies. Faster-X evolution may explain the phylogenetic positive association between the extent of sex chromosome heteromorphism and reproductive isolation. However, in most of these studies faster rates of X evolution are not conclusively associated with hemizygosity, and may represent a pattern of X evolution that is not caused uniquely by the uncovering of recessive adaptive alleles. For example, the disproportionate role for the X has been observed in species without degenerate Ys such as Drosophila miranda, mosquitos and European tree frogs. These results left the connection between hemizygosity, rates of molecular evolution and reproductive isolation on the X somewhat tentative.
Alternate research approaches estimating population-wide levels of gene flow offered an alternate and complementary approach to understanding the Large-X effect. Patterns of gene flow between populations is an important part of the study of speciation. One key insight of ‘the modern synthesis’ of the 1940s was to propose that reduced levels of gene flow between populations could allow for allele frequencies in these populations to diverge and thus for species to evolve different phenotypes. Studies of genetic gradients in phenotypes or allele frequencies, known as clines, complicated the concept of species as populations completely isolated from gene flow by finding gradual changes in allele frequencies across parapatric species’ boundaries. Furthermore, allele frequency clines were found to be heterogeneous across the genome, suggesting heterogeneity in gene flow across the genome. Using models where different loci have different clines, the X chromosome was frequently found to show steeper rates of differentiation than other genomic regions. Studies of clines across hybrid zones for loci on the sex chromosomes showed a disproportionately low amount of gene flow for the sex chromosomes in rodents, birds, crickets, but not toads with undifferentiated sex chromosomes. Hybrid cline analysis did much to question the impermeability of species boundaries.
The incorporation of continuous gene flow into models of speciation also led to the proposition that regions of the genome with low rates of recombination could allow for the maintenance of coadapted allele complexes, which would cause hybrid failures when in the wrong environment. This coadapted gene complex perspective of speciation led to a view known as ‘ecological speciation’, where local adaptation caused divergence between populations. Coadapted complexes were expected to show low rates of recombination as to keep alleles together. This conceptualization was supported by finding low rates of recombination across polymorphic chromosomal arrangements in hybrid zones, for example in sunflowers, Boechera stricta, mosquitos, birds and Drosophila. Multi-locus DNA sequencing further produced evidence confirming that speciation often proceeded with gene flow, and that gene flow was not restricted to narrow regions of contact between species. For example, the work of Wang, Hey and Wakeley (1997) showed not only that gene exchange between Drosophila species was frequent but also that there was heterogeneity in the amount of gene exchange between loci across the genome far beyond the regions of parapatry. Speciation with gene flow has been shown to occur in plants including monkeyflower, morning glories, and wild tomato and in insects including Drosophila and butterflies. Speciation seems to frequently occur with gene flow.
The recognition that gene flow between populations proceeds during multiple stages of divergence changed how genomes could be analyzed for patterns of population differentiation. Given growing evidence that speciation often proceeds with gene flow and suspecting that linked gene complexes were responsible, the idea became popular to look for genomic regions showing excess differentiation at neutral loci as selection for local adaptation was predicted to drag along linked neutral variation and therefore genomic regions showing high levels of neutral divergence were expected to be linked to complexes responsible for speciation. Early approaches did not consider the effects of purifying selection in regions of low recombination on metrics of divergence. Nonetheless, even after correcting for the effect of linked purifying selection, sex chromosomes showed evidence for being disproportionately differentiated in rabbits, birds, Silene, and Heliconius butterflies but not in the mating-type loci of haploid anther-smut fungi. Even when looking at patterns of gene flow in allopatric populations, the X chromosome appeared as a genomic centre of differentiation.
In addition to the dominance hypothesis, another explanation is that sex chromosomes pleiotropically appear as hubs of divergence due to their inherent association to sex phenotypes. The presence of separate males and females is associated with increased diversification and speciation in animals, but the pattern is unclear in plants. Sex chromosomes may show patterns of divergence by pleiotropy if the loci on sex chromosomes play a disproportionate role in local adaptation, especially if local adaptation is sex-specific. Alternatively, sex-specific differences in natural selection may be important in the origin of species. As highlighted in a previous post, sexual antagonism can lead to conflict between alleles with opposite fitness effects in each sex. This conflict can cause genes involved in sexually antagonistic traits to evolve more rapidly, and their accelerated evolution may pleiotropically cause incompatibilities between populations. Importantly, if sexual conflict is resolved with the fixation of different alleles that are incompatible in different populations, conflict can lead to hybrid failure and population divergence. For example, in yellow monkeyflower Mimulus selection on male function in pollen is likely to play an important role in reproductive isolation. In Drosophila, genes with sex-biased expression and X-linkage have faster rates of adaptive protein evolution. Sex-specific evolution could cause patterns of differentiation in any genomic region with an association with sex, and many such genes are likely to be on the sex chromosomes.
Sex chromosomes are likely hubs for conflict during meiosis as well. In 1881, Roux conjectured a theory called Kampf der Theile im Organismus (“Battle of parts in the body”) in which he proposed that, as a reasonable extension of evolution by natural selection, we should expect every part of an organism to compete against every other part for survival. Haldane extended Roux’s Kampf der Theile theory to include a battle between every gene, proposing that “the process continues until natural selection or the increased activity of other genes puts a stop to it” (Haldane, 1933, p.15). Because sex chromosomes are inherited in a sex-specific manner and meiotic drivers most often have sex-specific effects, meiotic drivers are most likely to spread in the population when they are linked to the sex chromosomes. For example, elements that can bias their segregation away from the polar bodies during female meiosis are most likely to spread through a population if the element is inherited more often by females, and therefore linkage to the sex determining region is favoured. Particularly surprising is the conclusion that, despite potentially imposing substantial fitness costs upon an organism, selfish genes can be very successful. The appealing aspect of ‘selfish genetics’ is that it can explain invasion of alleles that otherwise have substantial fitness costs. Selfish elements have been associated with speciation. Indeed, regions experiencing female meiotic drive have been observed to be more divergent between populations and to cause hybrid failures in several plants. This model would suggest that even without apparent sexually dimorphic phenotypes, sex-specific action during meiosis could cause the sex chromosomes to appear as regions disproportionally contributing to speciation.
The sex chromosomes are deeply intertwined with the process of speciation. Unmasking of genes causing incompatibilities between populations, and of recessive adaptive alleles by a degenerate Y, can cause heterogametic hybrids to fail more often and also cause hybrids with a foreign X chromosome to fail more often. Loci on the X seem to often evolve faster than the rest of the genome and both sex-specific evolution and unmasking of adaptive alleles may contribute. Analyses of gene flow across the landscape suggest the patterns of hybrid failure on the X in the lab may be associated with real impacts in natural populations. Allele frequencies change faster across space on the X and X haplotypes are under-represented in foreign genomes. These patterns are likely to have a composite underpinning arising from both Y degeneration and faster rates of evolution in genes associated with intersexual conflict, including during meiosis.