At the turn of the twentieth century, evidence supporting chromosomes as the material basis for heredity cemented Mendel and Darwin as the grandfathers of a nascent discipline: evolutionary genetics. The switch in biology to a molecular basis for heritability and for evolution left a massive gap in theory in the field, but also opened a vast landscape for empirical exploration. During this period were discovered three correlates of sex chromosomes that thereafter would need to be accounted for in any holistic theory for the evolution of sex chromosomes: low rates of recombination, disproportionate population differentiation, and degeneration. Establishing whether and how much these observations related to each other took a century’s worth of work. Parts remain unresolved. In this section, I review the studies of the early 1900s that lay the foundations for our current understanding of sex chromosomes. In the following sections, I review the next century’s work to understand these three observations.
The first sex chromosomes were observed in insects. In 1905, cytological study led N. Stevens to conclude that a dimorphic pair of chromosomes was associated with sex phenotype in the mealworm Tenebrio molitor (Stevens 1905; Wilson 1905). “It seems certain that an egg fertilized by a spermatozoön which contains the small chromosome must produce a male, while one fertilized by a spermatozoön containing […] chromosomes of equal size must produce a female” (Stevens, 1905, p.18). Working with a related insect group, Hymenoptera, E.B. Wilson also concluded “a causal connection of some kind exists between the chromosomes and the determination of sex” (Wilson, 1905, p.501). These two scientists were the first to find organisms for which males had a dimorphic pair of chromosomes where, in females, the same pair was evenly sized. In an international lecture in 1909, Wilson proposed that each chromosome of the homomorphic pair be called an ‘X’ chromosome, while the heteromorphic male-specific chromosome be named a ‘Y’ chromosome (Wilson 1909).
The studies by Stevens and Wilson were the culmination of a decade of work on the heritability of sex phenotypes. Before the discovery of sex chromosomes, it was generally believed that sex was induced by environmental conditions. These theories proposed sex was determined by temperature at conception (Aristotle n.d.; Galen n.d.; Gordon 1979), by the quality of the mother’s diet (Geddes 1889; Cuénot 1899) or, by which testicle contributed the sperm that fertilized the egg (Zirkle 1957). A series of works at the turn of the 20th century changed this view. These studies showed that each sperm from a male Pyrrhocoris firebug could be categorized into one of two size classes, and that each sperm class predictability produced zygotes of one sex (Henking 1891). Work by McClung in Xiphidium locust in 1899 extended this project by finding that having an unpaired chromosome defined the male-determining sperm class (Mcclung 1899). Considering that sperm size class correlated strongly with the sex of the zygote, McClung concluded that it was specifically the presence/absence of a chromosome in the sperm that dictated whether a zygote was most likely to develop to be female or to be male (McClung 1902). The work by Stevens and Wilson expanded McClung’s hypothesis by suggesting that, in some cases, sex chromosomes were paired, like other chromosomes, but that the male determining chromosome was heteromorphic. Together, these works provided strong evidence that some sex phenotypes were determined by chromosomes. While it could have been argued sex chromosomes were an oddity specific to insects, by 1915 the list of species with evidence of sex-linked chromosomes included humans, cats, some birds, a fish, Drosophila ampelophila (Later renamed Drosophila melanogaster), some moths, and the plant Lychnis dioica (Later renamed Silene dioica) (Morgan et al. 1915). The list of species with evidence of sex chromosomes today is considerably more extensive (Bachtrog et al. 2014). For detailed information, see the Tree of Sex consortium (http://treeofsex.org/) whose aim is to overlay sex determination information on complete a phylogeny of eukaryotes.
The contribution of some chromosomes to sex phenotypes supported the concurrently developed chromosomal theory of heredity. In 1902, W.S. Sutton (Sutton 1902) and T. Boveri (Boveri 1902, 1904) proposed that chromosomes were the cytological basis for all heritability. Working with Brachistola grasshoppers and Echinus sea urchins respectively, Sutton and Boveri’s studies showed that one from each pair of a parent’s chromosomes passed unchanged to offspring. Offspring missing chromosomes were often inviable, infertile or otherwise significantly irregular. Together, these findings suggested that a set of molecules was inherited by an offspring from its parents which, paired, held the instructions to form that offsprings’ body. The discovery that one pair of chromosomes defined sex supported the hypothesis that the full set of chromosome would inform the complete development of the body.
The chromosomal theory of inheritance elegantly demonstrated the expectations from Mendel’s theory of inheritance. In the mid-1800s, Mendel proposed a system of inheritance which contended that traits were inherited as units (Mendel 1866), in contrast to the then popular idea that an offspring’s traits were a blend of the parents’ traits.The discovery of sex chromosomes and the proposal of the chromosomal theory of inheritance coincided with the rediscovery of Mendel’s work by C.E. Correns (Correns 1900), E. von Tschermak, and H. de Vries (Vries and Marie 1900). Inspired by the rediscovered work, W. Bateson was able to use Mendel’s proposed system of inheritance to explain inheritance patterns for many phenotypes, including hairiness in Lychnis, seed colour in corn, extra toes in fowl, and even some behaviour in mice (Bateson and Saunders 1902). Similarly, Correns proposed Mendelian analysis could explain the connection between sex chromosomes and sex phenotypes (reviewed in (Wilson 1909)). Given females were homozygous for the X while males were heterozygous, maleness held to the expected pattern of inheritance for a dominant trait. This connection between sex chromosomes and sex phenotypes was one of the first pieces of concrete evidence that Mendelian and chromosomal heredity were tenable and related.
The finding of a material basis for Mendelian heritability supported Darwin’s theory of evolution by natural selection. Before the rediscovery of Mendel, the blending theory of inheritance was a significant difficulty for Darwin’s theory of natural selection. Darwin predicted that natural selection required phenotypic variation to allow a system to evolve, yet under blending inheritance, most phenotypic variation was erased each generation because parental phenotypes blended into each other (Jenkin et al. 2014). The theory of blending inheritance predicted that sex phenotypes were unlikely to be heritable because an offspring’s sex phenotypes were observably more similar to that of their parent’s of the same sex than to that of a blend of both parents. Mendel’s modular view of inheritance allowed for a substantially more effective explanation for the maintenance of variation (Lock 1906), as was required for the functioning of Darwin’s theory. Rather than the regression towards the mean predicted from blending inheritance, consideration of Mendel’s laws predicted that genotypes could be maintained at equilibrium by the continuous separating and joining of alleles with each generation, as shown formally by Hardy (Hardy 1908) and by Weinberg (Weinberg 1908).
Given their previously fringe status when sex chromosomes were first discovered, neither Darwin’s theory of natural selection nor Mendel’s theory of inheritance had been sufficiently developed to make predictions regarding the existence, let alone the nature nor the evolution, of sex chromosomes. Nonetheless, studies of sex chromosomes went forward. For several years, scientists, mostly studying Drosophila fruit-flies, rigorously studied sex chromosomes without expectations to what they might discover. It was one of the few times in the history of the study of evolution where empiricism came before theory. Three germinal findings, discovered in rapid succession, defined our current understanding of sex chromosomes.
Continued study in Drosophila revealed traits were not all inherited independently. Mendel’s theory of inheritance proposed, first, that each trait was reducible to paired constituents, but, second, that the inheritance of separate traits was independent. Yet, student’s of the chromosomal theory of inheritance foresaw that “since the number of inheritable characters may be large in comparison with the number of pairs of chromosomes, we should expect actually to find […] cases in which characters are linked together in groups in their inheritance” (Morgan, 1915, pp. 6). Indeed, contrary to the expectations from Mendel’s second postulate, it was discovered that the inheritance of separate traits was frequently correlated. For example, studies of Drosophila mutants revealed that separate eye color mutations were inherited together more often than expected by chance (Morgan 1911a). Traits inherited together were referred to as ‘linked’. These findings suggested that rather than each being inherited independently, traits were inherited in groups. In support of this idea, Drosophila researchers found that rather than the number of traits reflecting the chromosome count, the chromosome count fit well with the number of groups of correlated traits (Morgan et al. 1915).
While certain traits were more likely to be inherited together, the likelihood of joint inheritance differed between different traits. T.H. Morgan proposed that linkage could be broken down over evolutionary time by events called ‘crossovers’ (Morgan 1910; Robbins 1918). During crossover events, the genetic material was shuffled between homologous chromosomes. Furthermore, Morgan proposed that the probability of joint inheritance reflected the physical distance on the chromosome between the loci responsible for each trait (Haldane 1919). Supporting Morgan’s theory, F. Janssen’s ‘chiasmata’ theory proposed chiasma, joints between homologous chromosomes observable under the microscope, were the physical observation of crossover between homologous chromosomes (Janssens 1909; Creighton and McClintock 1931). In 1931, B. McClintock showed crossover and chiasma distances were indeed correlated in maize (Creighton and McClintock 1931).
While the linkage between most phenotypes was variable, male-specific phenotypes were discovered to be completely linked in Drosophila (Morgan 1910, 1911b; Morgan et al. 1915). The linkage of all male-specific mutations led to the conclusion of a complete absence of crossovers in Drosophila males. While the absence of crossovers in males has not been found to be universal in Eukaryotes, the linkage of some sex-specific mutations is generalizable to many other systems (Bachtrog et al. 2014). Indeed, the absence of crossovers between at least part of the X and the Y has been found to be a defining characteristic of sex chromosomes (Morgan et al. 1915). This conclusion has been supported by studies finding that, although the X and Y can often pair at meiosis, chiasma between the X and Y are very few and are relegated to the tips of sex chromosomes (Darlington 1934).
The second generalization about sex chromosomes is that genes on Y chromosomes are more often deleterious or otherwise degenerate than elsewhere in the genome. This was first noted by H.J. Muller, the first to find any evidence of a trait linked to the Y (Muller 1914). The disproportionately few number of traits mapping to the Y as compared to the rest of the genome, as well as its relatively small size, led Muller to propose that “genes are degenerate or entirely absent” on the Y chromosome. Another line of evidence also supported the proposal that the heteromorphic chromosome could have a significant negative effect on fitness or viability: studying the plants Silene and Rumex, Correns had found that male-determining pollen was less competitive than female-determining pollen in male heterogametic systems (Correns 1924). As pollen is haploid, the unmasking of absent or degenerate gene copies on the Y could cause Y-bearing pollen to be less competitive (Smith 1964; Lloyd 1974). A third line of evidence was found in studies of speciation.
The third correlate of sex chromosome evolution was their disproportionately participation in population divergence and speciation. In a 1922 survey of hybrid failure, Haldane observed that in interspecific crosses where one sex was more often sterile or inviable, the less fit sex was always the heterogametic sex (Haldane 1922). This observation came to be known as ‘Haldane’s rule’ (Coyne and Orr 1989). Haldane’s rule incriminated the Y once more in lowering male fitness, this time in hybrids, but also suggested sex chromosomes played a disproportionate role in isolation between species. The connection between speciation and the sex chromosomes was soon discovered to extend past Haldane’s rule. Between 1934-1936, T. Dobzhansky ran a series of experiments searching for the loci causing hybrid failure in crosses between Drosophila species (Dobzhansky 1934, 1936). Dobzhansky’s studies returned a disproportionate number of loci responsible in hybrid failure on the X chromosome compared to the rest of the genome. This result, known as the the ‘Large X effect’, has been replicated in many independent species pairs (Charlesworth et al. 1987; Coyne and Orr 1989). Together, Haldane’s rule and the Large X effect support an important role for the sex chromosomes in population differentiation.
In sum, three rules appear to be true of many independent sex chromosomes. First, the X and Y chromosomes do not crossover. Second, Y alleles are often degenerate or entirely missing. Third, the sex chromosomes disproportionately participates in population differentiation and speciation. The search for the molecular and evolutionary explanation for these three simple observations has revealed complex and inter-related processes, as I review in the next three sections.
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