The discovery of sex chromosomes, at the turn of the twentieth century, significantly shaped not only how we study sex chromosomes today but also the fields of genetics and evolution more broadly. The first heteromorphic chromosomes to be correlated with sex phenotypes were observed in insects. In 1905, cytological study led N. Stevens to find that a dimorphic pair of chromosomes was associated with sex phenotype in the mealworm beetle Tenebrio molitor. Working with the related insect group, the Hymenoptera, E.B. Wilson also concluded a causal connection between oddly-shaped chromosomes and sex determination. 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. Heteromorphism between the sex chromosome allowed X and Y, respectively, to be tracked across meioses, enabling a direct connection to be made between chromosomal segregation and phenotype.
The studies by Stevens and Wilson were the culmination of a decade of work on the inheritance of primary sex phenotype. Before the discovery of sex chromosomes, it was generally believed that sex was induced by environmental conditions. These theories proposed that sex was determined by a variety of factors including temperature at conception or quality of the mother’s diet, among other theories. A series of studies at the turn of the 20th century radically changed this view. Study by H. Henking in 1891 showed that each sperm from a male Pyrrhocoris firebug could be categorized into one of two size classes, and that each sperm class predictably produced offspring of one sex. Work by McClung on sperm in the Xiphidium locust in 1899 extended this project by finding that the sperm from the male-determining class had one less chromosome than the female determining class. Considering that sperm size class correlated strongly with the sex of the offspring, McClung concluded that it was specifically the presence or absence of a chromosome in the sperm that dictated whether a zygote was most likely to develop to be female or male, respectively.
The work in 1905 by Stevens and by Wilson expanded McClung’s hypothesis by suggesting that, in some species, male-producing sperm carried a full chromosome set, but that one chromosome was much smaller than its partner chromosome. Together, these studies provided strong evidence that sex phenotype could be determined by chromosomes. By 1915, the list of species with evidence of sex-linked chromosomes included humans, cats, birds, fish, Drosophila ampelophila (now D. melanogaster), moths, and the plant Lychnis dioica (now Silene latifolia), suggesting sex chromosomes were not an unusual characteristic specific to insects. Furthermore, heteromorphic sex chromosomes were not exclusive to males: females were discovered to have heteromorphic sex chromosomes in birds and moths. The list of species with evidence of sex chromosomes today is considerably more extensive. In an international lecture in 1909, Wilson secured the names for each of the sex chromosomes: each in the homomorphic pair would be called an ‘X’ chromosome, inspired by Henking’s 1891 ‘x-element’, while the heteromorphic male-specific chromosome would be named a ‘Y’ chromosome. For cases where the female was heterogametic, the chromosomes were dubbed Z and W, such that males were ZZ and females ZW.
The discovery that chromosomes contributed to sex phenotypes caused a revolution in the study of evolution. First, the discovery of sex chromosomes supported W.S. Sutton’s and T. Boveri’s concurrently developed chromosomal theory of heredity. Besides supporting the chromosomal theory of inheritance, sex chromosomes elegantly demonstrated the expectations from Mendel’s theory of inheritance, in contrast to the then popular idea that an offspring’s traits were a blend of the parents’ traits. In support of Mendel’s principles, Correns proposed Mendelian analysis could explain the connection between sex chromosomes and sex phenotypes: given females were homozygous for the X while males were heterozygous X-Y, maleness was the expected pattern of inheritance for a dominant trait on the Y. This connection between sex chromosomes and sex phenotypes was one of the first pieces of concrete evidence that Mendelian and chromosomal heredity were both tenable and probably inseparable. Finally, the evidence supporting a material basis for Mendel’s theory of heritability also significantly strengthened Darwin’s theory of evolution by natural selection, as Mendel’s view of inheritance allowed for a substantially more effective explanation for the maintenance of variation than blending inheritance. The agreement between Darwin’s and Mendel’s theories revolutionized biology and began a new era.
Given the previously fringe status of Darwin’s theory of natural selection and Mendel’s theory of inheritance at the time when sex chromosomes were first discovered, neither theory had been sufficiently developed to make predictions regarding the existence, the nature, nor the evolution of sex chromosomes. Nonetheless, studies of sex chromosomes went forward. For several years, scientists, mostly studying Drosophila fruitflies, rigorously studied sex chromosomes without expectations to what they might discover. Three germinal findings defined our current understanding of sex chromosomes.
The first generalization to be made about sex chromosomes was that X homologs on Y chromosomes were more often missing than in other chromosome pairs. The uniqueness of the Y was first noted by the marked size dimorphism between X and Y and then by finding a lack of phenotypes associated with the Y. The Y was proposed to be missing most genes, as was supported by the unmasking, in males only, of X-linked lethal factors and by the observation of inviability in synthetic YY individuals of Drosophila and Lebistes guppies, or infertility as in Mercurialis. However, it was not clear why the Y should be gene depauperate.
The second finding was born from the nascent study of linkage mapping. Study of genetics in Drosophila revealed not all traits were inherited independently. Indeed, the likelihood of joint inheritance of variants was found to differ between different traits. T.H. Morgan proposed that linkage between Mendelian traits could be broken down over evolutionary time by shuffling loci between paired chromosomes in events called ‘crossovers’, and that the probability of joint inheritance of variants reflected the physical distance on the chromosome between the loci responsible for each trait. Supporting Morgan’s theory, F. Janssen’s proposed ‘chiasma’, joins between homologous chromosomes observable under the microscope, as the physical observation of crossover between homologous chromosomes. In 1931, B. McClintock showed that, in maize, crossover and chiasma distances were indeed correlated, and therefore likely to represent the same phenomenon.
While linkage was generally variable, male-specific phenotypes were discovered to be completely linked in Drosophila. 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. This conclusion is supported by studies demonstrating that although the X and Y can often pair at meiosis, chiasma between the X and Y are absent or, when very few exist, chiasma are relegated to the tips of chromosomes. The absence of crossovers and chiasma between at least part of the X and the Y has been found to be a defining characteristic of sex chromosomes.
The third correlate of sex chromosomes was a disproportionate participation in the process of 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, most often the male. This observation came to be known as ‘Haldane’s rule’. Haldane’s rule incriminated the Y once more in lowering male fitness, this time in hybrids, but also suggested sex chromosomes could play a role in reproductive isolation between species. Further investigation into the genetic underpinning of sex-specific hybrid failure uncovered a deeper connection between reproductive isolation and the sex chromosomes. Between 1934-1937, T. Dobzhansky conducted a series of experiments searching for the loci causing hybrid failure in crosses between Drosophila species. Dobzhansky’s studies found a disproportionate number of loci responsible for hybrid failure on the X chromosome compared to the rest of the genome, regardless of sex. This result, known as the ‘large X effect’, has been replicated in many independent hybridizing species pairs. Together, Haldane’s rule and the large X effect support an important role for the sex chromosomes in population differentiation and speciation.
In sum, three rules appear to be generally true of the evolution of independent sex chromosome systems and suggest these are due to convergent evolutionary mechanisms. First, Y alleles are often degenerate or entirely missing. Second, at least part of the X and Y chromosomes do not crossover with each other. Third, the sex chromosomes disproportionately participate in population divergence and speciation. The search for the evolutionary and molecular explanations for these three simple observations has revealed complex and inter-related processes.