Chromosomal Theory of Inheritance

The chromosomal theory of inheritance is the idea that genes, the units of heredity, are physical in nature and are found in the chromosomes. The theory arose at the turn of the twentieth century, and became one of the cornerstones of the modern understanding of genetics.

The Birth of a Science

Charles Darwin first conceived the idea of hereditary units when he published his theory of pangenesis in 1868. In this model, circulating units called gemmules are accumulated in the gonads and transmitted to the off-spring. This theory was discredited by experimental tests performed by Francis Galton in the 1870s. Galton used blood transfusions in rabbits to show that the alleged gemmules in one rabbit's blood did not alter the heredity of the recipient rabbit's blood. In the 1890s Hugo de Vries took the term "pangenesis" and trimmed it to "pangene" for the assumed units of inheritance. He argued that pangenes remained inside the cell and did not migrate. It was this theory of intracellular pangenesis that led de Vries to independently find what Gregor Mendel had discovered thirty years earlier in his work with contrasting traits in garden peas—there are units of inheritance that are transmitted by reproduction. Wilhelm Johansson introduced the term "gene" to replace several contending and misleading terms for the basic unit of heredity in 1909. The term "genetics" came earlier, when William Bateson coined the word in 1906 to represent the new field that studied heredity, variation, and evolution. The terms "gene," "genetics," and the biblical term "genesis" all share a common Latin root, gen, meaning origin.

Mendel identified what he called "factors" (later called genes) as the underlying cause for the appearance of certain traits in peas. He described them as stable units that seemed to disappear in a hybrid (a plant grown from a cross between two parent plants that show differing traits) but would reappear among some of the progeny of such hybrids. Mendel identified two laws—the law of segregation and the law of independent assortment—which together governed the movement of factors from parent to progeny . This strongly suggested that the factors of inheritance were discrete physical objects. Shortly before Mendel's work was being rediscovered, advancements in the construction of microscopes had allowed scientists to make careful observations of cell division. This led to the discovery of colored bodies in the cell nucleus that appeared to double and divide just before each division. These were called chromosomes ("colored bodies").

By 1902 the chromosome movements during meiosis had been worked out, and Walter Sutton used them to explain Mendel's laws. He argued that the pairing and separation of homologues would lead to the segregation of a pair of factors they carried. Thus, to use one of Mendel's own experiments, hybridizing yellow and green pea plants would yield one yellow and one green gamete apiece. (A gamete is germ cell, sperm or egg, that contains half of a full complement of chromosomes, originating from one of the parent plants.) The result is a gametic ratio of 1:1. The union of pollen and ovules would result in the 3 yellow to 1 green Mendelian ratio. Similarly, two different pairs of homologs would yield the 9:3:3:1 ratio associated with Mendel's law of independent assortment. Sutton called his union of cytology with Mendelian breeding analysis the "chromosome theory of heredity."

X-Linked Inheritance in Hybrids

Beginning in 1907, Thomas Hunt Morgan extended Sutton's insights by conducting laboratory studies of the fruit fly, Drosophila melanogaster. With his students Alfred Henry Sturtevant, Calvin Blackman Bridges, and Hermann Joseph Muller, he established what is now called classical genetics. Morgan and his students found new phenomena that added to Sutton's chromosome theory of heredity. The first finding, achieved in 1920, was X-linked inheritance, in which white-eyed flies showed a sex-linked inheritance of the trait in a modified 3:1 ratio. In other words, cross-breeding hybrid red-eyed flies resulted in all the female offspring having red eyes, whereas half the male offspring had white eyes.

Morgan's team explained this modified ratio by proposing that the eye-color genes are carried on the X chromosome, of which females have two but males have only one. The female's two X chromosomes can be homozygous (the genes carried are AA or aa) or heterozygous (the genes carried are Aa) for an X-linked gene. Males are always homozygous, because the small Y chromosome lacks almost all the genes found on the X chromosome. Thus, they can carry only one gene for the trait: AY or aY. Since males can carry no second copy of the gene for the trait, they will express the white-eyed trait if they inherit the gene for it from a hybrid red-eyed parent. This discovery further strengthened the case in favor of the chromosomal theory of inheritance.

Several additional X-linked mutations arose by 1913. Morgan reported that these mutations produced unusual ratios when subjected to breeding analysis. He explained these findings by proposing that genes could trade places between two homologous chromosomes. Morgan's finding, called crossing over, was used to map the genes along the length of the X chromosome, and Sturtevant used Morgan's data to construct the first linkage map. Working independently, maize geneticists, especially Barbara McClintock, later demonstrated the same phenomenon.

Further Advances in Theory

Also from 1913 to 1916, Bridges found some exceptions to the expected modified 3:1 ratio for white-eyed flies. He inferred, and confirmed by microscopic examination of cells, that these unexpected departures arose from the failure of homologous chromosomes to separate during meiosis. Bridges called this phenomenon nondisjunction and used it as a proof of the chromosome theory of heredity.

While both Mendel and Morgan's group worked with simple, single-gene traits, the relation of genes to most character traits turned out to be more complex. A successful analysis of this was presented by Muller. He argued that the variable wing shapes and lengths of beaded and truncated wings in fruit flies involved several factors. A chief gene was essential, but it required modifier genes that could intensify or diminish its expression. By combining different modifier genes and the chief gene in two parents, Muller could predict the percentages of wing shape and length among the progeny. Muller used this analysis to support a Darwinian model of natural selection of character traits whose variations owe their origins to the highly heterozygous state of natural populations and to new mutations that arise in each generation. Muller's analysis added evolution to cytology and breeding analysis as the three tributaries of classical genetics.

see also Epistasis; Fruit Fly: Drosophila ; Linkage and Recombination; Mcclintock, Barbara; Mendel, Gregor; Morgan, Thomas Hunt; Nature of the Gene, History.

Elof Carlson

Bibliography

Allen, G. E. Thomas Hunt Morgan: The Man and His Science. Princeton, NJ: Princeton University Press, 1978.

Judson, H. P. The Eighth Day of Creation: The Makers of the Revolution in Biology. New York: Simon & Schuster, 1979.

Morgan, Thomas Hunt, et al. The Mechanism of Mendelian Heredity. New York: Holt Reinhart & Winston, 1915. Reprinted by Johnson Reprint Corporation with an Introduction by Garland E. Allen, 1978.

Sturtevant, Alfred Henry. A History of Genetics. New York: Harper & Row, 1965.