The Boveri-Sutton Theory Links Chromosomes to Heredity
The Boveri-Sutton Theory Links Chromosomes to Heredity
Cytologists had established links between cell theory and theories of evolution and heredity by the beginning of the twentieth century. The work of Walter S. Sutton (1877-1916) and Theodor Boveri (1862-1915) provided sound cytological evidence for the individuality of the chromosomes and suggested that they might play a role as the carriers of hereditary factors. Studies of sex determination in insects by Nettie M. Stevens (1861-1912) and Edmund B. Wilson (1856-1939) also supported the idea that chromosomes served as the material basis of biological inheritance.
By the beginning of the twentieth century, cytologists had established links between cell theory and theories of evolution and heredity. Painstaking investigations of the fine structure of the cell convinced scientists that the cell nucleus was very different in form and function from the cytoplasm. Indeed, in terms of theory as well as empirical observations, cytology played a major role in establishing the structural basis of Mendelian genetics. The availability of new methods for preparing and staining biological preparations made it possible to see the nucleus and the bodies known as chromosomes during cell division. These observations indicated that the nucleus must have a fundamental role in heredity as well as the development and growth of the organism.
A valuable theoretical framework that guided studies of cytology and heredity had been proposed by the great theoretician of biology August Weismann (1834-1914) in the 1890s. Analyzing the key questions of evolutionary theory, variation, and inheritance, Weismann concluded that the stability of inheritance between generations was the most significant feature of heredity. Heredity had to be studied at both the level of the cell and the individual before it could be understood in terms of evolving populations. Weismann proposed the theory of the continuity of the germplasm. He also predicted and explained the necessity for a form of reduction division of the chromosomes during the formation of germ cells. Although Weismann knew nothing about the chemical nature of the germplasm, his theories provided a valuable framework for studies of the components of the cell, particularly the division of the nucleus and the chromosomes. When somatic cells divide, he theorized, the number of chromosomes must remain constant. When germ cells are produced, he continued, some mechanism is needed to divide the number of chromosomes by half; when fertilization occurs and the egg and sperm nuclei fuse, the normal chromosome number is restored.
By the turn of the century, microscopic observations of cell division seemed to vindicate Weismann's predictions. Moreover, both cytologists and geneticists were ready to accept the idea that there was a relationship between the factors studied in breeding experiments and the behavior of the chromosomes during cell division (mitosis and meiosis). Although cytologists knew that chromosomes occurred in pairs that seemed to join and separate during cell division, the nature of chromosomes was not understood. Some biologists thought that each chromosome carried all the hereditary units that were needed to form a complete individual, but it seemed possible that the maternal and paternal chromosomes might remain as distinct groups. By 1910 some biologists were sure that paired hereditary factors might actually be located on the chromosomes pairs contributed by the egg and the sperm. Cytological evidence for this conclusion was provided by the work of Walter S. Sutton and Theodor Boveri. Studies of sex determination in insects by Nettie M. Stevens and Edmund B. Wilson also supported the idea that the chromosomes provided the material basis of heredity.
Theodor Boveri used doubly fertilized sea urchin eggs to investigate the function of the chromosomes in germ cell formation and embryological development. By studying the fate of embryos with abnormal numbers of chromosomes, Boveri was able to test the idea that each chromosome carried all character traits. Boveri found correlations between the abnormal combinations of chromosomes and the peculiar development of these embryos. Although Boveri could not determine the role of specific chromosomes, his observations indicated that the chromosomes were not identical to each other. His early experiments were described in his classic paper, "Multipolar Mitosis as a Means of Analysis of the Cell Nucleus" (1902).
Walter Sutton was able to use studies of the behavior of the sex chromosomes of certain insects as a way to extend the observations that Boveri had made with random combinations of chromosomes. As a student of Clarence E. McClung (1870-1946), a pioneer in the study of the sex chromosomes, Sutton knew that he could focus on specific morphological differences among the chromosomes of grasshoppers. As early as 1902 McClung had suggested that a special chromosome, known as the "accessory chromosome," determined whether an individual was male or female.
Some cytologists thought that the apparent individuality of the chromosomes might be lost between cell divisions when the chromosomes seemed to disappear and become tangled masses of chromatin threads. Although there was no empirical evidence to prove that the same chromosomes appeared at the next cell division, Sutton believed that the regularity in the size and shape of the chromosomes at each cell division indicated that the chromosomes maintained their individuality. In 1903, while he was Edmund B. Wilson's graduate student, Sutton published his landmark paper, "The Chromosomes in Heredity." He asserted that the behavior of pairs of chromosomes indicated that they did indeed represent the physical basis for the Mendelian factors, or genes. Sutton also suggested that the random assortment of different pairs of chromosomes might explain the independent segregation of pairs of genes. Surprisingly, Sutton decided to become a practicing physician rather than pursue a career in research. Other researchers, however, were also involved in cytological studies of the nature of the sex chromosomes.
Within the first decade of the twentieth century, cytologists provided key insights into the relationship between specific chromosomes and sexual differentiation. Microscopic studies of specific "unpaired" chromosomes suggested that the presence or absence of these "accessory," or "X," chromosomes might determine sex in various insects. Nettie Stevens and Edmund Wilson confirmed this hypothesis in 1905. Nettie Stevens had earned her B.A. (1899) and M.A. (1900) at Stanford University. She performed her doctoral research at Bryn Mawr and was awarded her Ph.D. in 1903. Bryn Mawr was a small woman's college, but two of America's leading biologists, Edmund B. Wilson and Thomas Hunt Morgan (1866-1945), were faculty members. Morgan taught at Bryn Mawr until 1904 and kept in touch with Wilson, who had moved to Columbia University in 1891. After earning her Ph.D., Stevens won a fellowship that allowed her to study abroad and work with Theodor Boveri at the University of Würzburg. When she returned to Bryn Mawr, she received a grant from the Carnegie Institution of Washington that made it possible for her to devote all her time to her research on the sex chromosomes of the common mealworm. (Because Stevens used her initials when she published her research results, many scientists were surprised to discover that N. M. Stevens was a woman.) The objective of her research was to clarify the relationship between the behavior of the chromosomes and the laws of Mendelian genetics.
Stevens demonstrated that the somatic cells of female mealworms contained twenty large chromosomes, while the cells of the male meal-worm contained nineteen large chromosomes and one small one. She reasoned that sex determination might be determined by some unique property of the unusual chromosome pair. Half of the spermatozoa produced by these male insects contained ten large chromosomes while the other half contained nine large chromosomes and one small one. The eggs that were fertilized by the sperm containing ten large chromosomes produced females; eggs fertilized by sperm carrying the small chromosome developed into males. (The large sex chromosome is conventionally referred to as "X" and the corresponding small chromosome is "Y." Females are XX and males are XY.) Stevens concluded that there must be a fundamental difference between the X and Y chromosomes and that this difference follows Mendelian rules of inheritance. Shortly after Stevens's paper on the chromosomal nature of sex determination was published, Wilson confirmed her conclusion through his research on a species in which the male had one fewer chromosome than the female, rather than a small Y chromosome.
The work of Boveri, Sutton, Stevens, and Wilson suggested that the chromosomes were distinctly individual in terms of their size, shape, and functional properties. Of course, cytological studies alone could not explain the precise nature of the chromosomes or the relationship between their chemical constituents and their role in carrying and transmitting genetic information. Nevertheless, these cytologists called attention to the way in which facts from cytology and Mendelian breeding studies could be integrated, forming the hypothesis that the hereditary Mendelian factors were physical components of the chromosomes. Moreover, the observations of these researchers suggested that each chromosome contained many Mendelian factors and that factors on the same chromosome would presumably be linked and thus always inherited together. This idea seemed to contradict the Mendelian law of independent assortment, but good evidence of linkage was discovered when more traits were subjected to breeding tests.
The Boveri-Sutton hypothesis explained or predicted many significant aspects of cytology and heredity, but many scientists remained skeptical of the implications of the chromosome theory of heredity. Wilson's experimental confirmation of the work of Sutton and Stevens was important in disseminating their conclusions to the scientific community. As author of the popular text The Cell in Development and Heredity and the friend and mentor of many prominent scientists, Wilson persuaded many skeptical scientists, including Thomas Hunt Morgan, to investigate the chromosome theory of heredity.
LOIS N. MAGNER
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