Alfred H. Sturtevant statistically analyzed crossing-over of six sex-linked traits of the fruit fly, Drosophila, to produce the first map of relative gene locations on chromosomes.

The beginning of the twentieth century was a period of considerable research in genetics. Charles Darwin and Alfred Russel Wallace had not been able to account for the variation between members of a species in their joint paper on evolution in 1859 and in their later work. Also, in 1900, Gregor Mendel’s work on transmission of traits was rediscovered. It was not known if Mendel’s research could be used to help explain the variation that allowed evolution to occur. Chromosomes;mapping
Genetics;chromosomes
[kw]Sturtevant Produces the First Chromosome Map (Fall, 1911)
[kw]First Chromosome Map, Sturtevant Produces the (Fall, 1911)
[kw]Chromosome Map, Sturtevant Produces the First (Fall, 1911)
Chromosomes;mapping
Genetics;chromosomes
[g]United States;Fall, 1911: Sturtevant Produces the First Chromosome Map[02870]
[c]Science and technology;Fall, 1911: Sturtevant Produces the First Chromosome Map[02870]
[c]Genetics;Fall, 1911: Sturtevant Produces the First Chromosome Map[02870]
[c]Biology;Fall, 1911: Sturtevant Produces the First Chromosome Map[02870]
Sturtevant, Alfred H.
Mendel, Gregor
Morgan, Thomas Hunt

Mendel had little idea of the physical location of the genes. By pure luck, he picked seven traits of garden peas whose genes were on separate pairs of chromosomes. This led to his law of independent assortment, Genetics;law of independent assortment which stated that genes for different traits will assort randomly in sperm or egg formation. Carl Correns reported an apparent exception to this law in 1900 in the plant Matthiola. He found that the trait of petal color tended to be linked to the trait for seed, leaf, and stem texture. Plants with colored flowers had a hoary texture, and plants with white flowers had smooth seeds. Although this exception seemed to disprove Mendel’s rule of independent assortment, the linked traits were actually caused by the genes for the two traits being on the same pair of chromosomes. Linked traits did not invalidate Mendel; they were merely an exception to his rule.

In 1910, Thomas Hunt Morgan reported the phenomenon of crossing-over Crossing-over, genetics[Crossing over]
Genetics;crossing-over[crossing over] of linked traits using Drosophila, the fruit fly. He realized that linked traits became unlinked. He had found that eye color and wing size were linked so that red-eyed flies had rudimentary wings and white-eyed flies had long wings. On occasion, however, he would get a fly with white eyes and rudimentary wings. Somehow, the linked traits had become unlinked. Morgan did his initial work with sex-linked traits. These traits are carried on the X chromosome. In Drosophila (and humans, for that matter), all eggs and male-producing sperm contain an X chromosome. This is a typical chromosome containing many genes. Females, thus, carry two X chromosomes in their body cells. Male-producing sperm carry a Y chromosome, which carries few, if any, genes. Therefore, all male flies have an X and a Y chromosome in their body cells.

Alfred H. Sturtevant first became interested in inheritance while breeding horses at his father’s ranch. While attending Columbia University, he had the opportunity to work in Morgan’s “fly room.” He then became interested in the process of crossing-over of sex-linked traits. He realized that the exchange between the X chromosomes most likely occurred during the synapsis (period in egg formation when two paired chromosomes lie next to each other) of meiosis (the process of sex cell formation). With sex-linked traits, crossing-over is significant only in egg formation. In sperm formation, the Y chromosome has few genes to cross over with its X partner. This somewhat simplifies the study of crossing-over, as one does not have to account for crossing-over in sex cell formation of the male parent.

Morgan reasoned that the relative distance between the genes could be determined by the frequency of crossing-over between them. Sturtevant proceeded to develop this concept and apply it to a real situation. An analogy using a rope to represent a chromosome and beads on the rope to represent genes explains this process. Imagine bringing two such ropes together and letting them intertwine. This is similar to what happens to the two X chromosomes in synapsis of meiosis. Assume bead A is at one end, bead B is 1 meter away, and bead C is at the other end, 5 meters away. Imagine that a child cuts equal portions of the ropes and ties each to the opposite rope. Assume that the child does not care where the cuts occur and cuts at purely random lengths. It is more likely that beads A and C will be separated by these cuts than it is that beads A and B will be separated, because of the larger distance between A and C. Using this reasoning, Sturtevant determined the distances between six sex-linked genes in Drosophila.

Sturtevant chose six sex-linked traits to study: First, trait A was body color. The dominant gene produced black bodies; the recessive condition gave yellow bodies. Second, trait B was eye color. The recessive condition gave white-eyed flies. The third trait, C, was closely related to trait B. If the dominant gene for trait B was present, then the dominant gene for trait C gave red eyes and the recessive gene gave eosin (pink) eyes. Flies having only recessive genes for trait B had white eyes, regardless of the gene for trait C. Trait D, the fourth trait, was also related to eye color. The dominant gene gave normal red eyes, the recessive condition gave vermillion eyes. The fifth and sixth traits were E and F for wing shape and size, respectively. If a dominant gene for both E and F was present, then the fly had normal wings. A fly with a dominant gene for E but no dominant gene for F had rudimentary wings; a fly with no dominant for E but a dominant for F had miniature wings. Finally, a fly having no dominants for either trait had both rudimentary and miniature wings.

If capital letters are used to represent the dominant genes for the six sex-linked traits and lowercase letters for the recessive genes, it follows that an X chromosome should contain either genes A, B, C, D, E, F or a, b, c, d, e, f. Crossing-over of chromosome fragments resulted in flies with other combinations on the X chromosome, such as A, B, C, d, e, f.

Using data collected from crosses in Morgan’s “fly room,” Sturtevant determined percentages of crossing-over between the various traits. For example, he found that crossing-over occurred between traits A and B 193 times out of 16,287 trials, or 1.2 percent. Crossing-over between traits A and F occurred 260 times out of 693 trials, or 37.6 percent. Sturtevant thus proved that the genes for traits A and B are much closer than the ones for A and F. Likewise, he established crossing-over frequencies between all the six traits.

In the crossing-over process, chromosomes meet (left) and recombine (right).

(Electronic Illustrators Group)

In order to describe his “map” of a chromosome, Sturtevant needed a unit of relative distance. He let one unit represent the distance between genes that cross over once in every one hundred times. Trait A was placed at one end of the chromosome map. Traits B and C were so close to each other that they never separated. He placed them ten units from trait A. Traits D and E were quite close to each other but could be separated. Trait D was 30.7 units from trait A. Trait E was 33.7 units from trait A. Trait F was at the other end of the chromosome and was 57.6 units from trait A. Therefore, a map showing relative distances between genes on chromosomes had been statistically derived.

Sturtevant also described double crossing-over in a 1914 publication. Sometimes chromosomes that have already crossed over with one another break at some other point and cross over again. If the genes A, B, and C are linked on a chromosome and a, b, and c on its partner chromosome, crossing-over might produce a chromosome with genes A, b, and c. Double crossing-over might then result in a chromosome with genes A, b, and C. This complicated the interpretation of the data, but was eventually clarified by Sturtevant.

Thomas Hunt Morgan was initially skeptical of the existence of genes because his experimental results often seemed to be contrary to Mendel’s laws. Sturtevant’s work helped convince Morgan that genes exist on chromosomes and that Mendel’s laws were valid. The apparent exceptions were now explainable by linkage and crossing-over and Mendel’s laws became firmly established among geneticists.

Sturtevant’s work spurred Morgan and his colleagues to pursue chromosome mapping of Drosophila. In 1915, Morgan’s group published a map showing the relative locations of fifty genes, including genes on the non-sex-related chromosomes (autosomes). In the 1930’s, interest in mapping led to maps derived by indirect physical observation of the genes of the giant chromosomes in the salivary glands of Drosophila. When properly stained and fixed on a slide, they showed cross patterns that could be correlated to specific genes. The physical maps did not correlate precisely to Sturtevant’s statistically derived ones, although the linear order of the genes was identical. It became apparent that some portions of chromosomes are easier to break than others.

Extensive maps of the four pairs of chromosomes of Drosophila have been made since Sturtevant’s first map, and similar interest developed in mapping human chromosomes. Because humans have a relatively large number of chromosomes compared with Drosophila and studies on human inheritance are strictly limited by ethical and legal considerations, traditional crossing-over studies were difficult, but new technology made this mapping feasible. Human cells can be grown in tissue cultures with mouse cells, and hybrid mouse-human cells will form with as few as one human chromosome. This allows researchers to examine and map the genes on this isolated chromosome. Another method of mapping genes makes use of a deoxyribonucleic acid (DNA) probe. DNA DNA, the building material of genes, is composed of chemical building blocks known as nucleotides. The nucleotide sequence of certain genes is known and can be detected on special photographs of a chromosome, so one can place a particular gene at a certain place on a chromosome by studying nucleotide patterns.

In 2003, the Human Genome Project Human Genome Project (HGP) concluded after thirteen years of research coordinated by the U.S. Department of Energy and the National Institutes of Health, along with other private-sector partners and contributions from numerous countries. The purposes of the HGP included identifying the more than twenty thousand genes in human DNA and the millions of chemical base pairs constituting DNA, storing and sharing these data, identifying means for improving the study of the data, and transferring biotechnology to the private sector, all the while taking into account the ethical, legal, and social impacts of such unprecedented research, including those surrounding the controversial issue of human cloning. Although concerns about such impacts persist, there is little doubt that the knowledge acquired during the HGP, along with the licensing of technologies to private-sector entities, has stimulated a multibillion-dollar biotechnology industry in the United States as well as the development of important new medical applications and therapies for genetic conditions and diseases. In 1911, when Sturtevant mapped six sex-linked genes on the Drosophila, he could not have guessed how far his first steps would take genetic science within the space of a century. Chromosomes;mapping
Genetics;chromosomes

• Cummings, Michael. Human Heredity: Principles and Issues. 6th ed. Monterey, Calif.: Brooks/Cole, 2002. This highly illustrated text aimed at nonscience students presents the complex topic of heredity clearly, without oversimplifying the concepts discussed. Also addresses the social, cultural, and ethical implications of the use of genetic technology.
• Edey, Maitland, and Donald C. Johanson. Blueprints: Solving the Mystery of Evolution. Boston: Little, Brown, 1989. Presents an interesting and understandable account of the advances in evolutionary theory from Linnaeus to the present, using analogies to explain complex concepts. Offers particularly good sections on genetics.
• Mader, Sylvia S. Biology. 8th ed. New York: McGraw-Hill, 2004. Biology text for beginning college students is clearly written and well illustrated. Devotes several chapters to genetics, ranging from classic Mendelian heredity to the latest molecular genetics. Good preview for anyone considering taking a genetics course.
• Morgan, Thomas Hunt. Evolution and Genetics. Princeton, N.J.: Princeton University Press, 1925. Dated, but provides useful information on advances in genetics up to the 1920’s in a manner accessible to high school biology students. Includes an interesting chapter on Mendel and his laws.
• Sturtevant, Alfred H. A History of Genetics. 1965. Reprint. Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory Press, 2001. A firsthand view of the development of classical genetics by a major participant. Rather technical in approach; might be of most value to the professional biologist. Mentions Sturtevant’s work with Morgan.
• _______. “The Linear Arrangement of Six Sex-Linked Factors in Drosophila, as Shown by Their Mode of Association.” Journal of Experimental Zoology 14 (1913): 43-59. The classic paper describing Sturtevant’s first mapping of genes on chromosomes. Written in a precise and scholarly manner, but surprisingly easy to understand. The sections on the mapping procedures and double crossing-over are fascinating.

Bateson Publishes Mendel’s Principles of Heredity

McClung Contributes to the Discovery of the Sex Chromosome

Sutton Proposes That Chromosomes Carry Hereditary Traits

Punnett’s Mendelism Includes Diagrams Showing Heredity

Bateson and Punnett Observe Gene Linkage

Hardy and Weinberg Present a Model of Population Genetics

Morgan Develops the Gene-Chromosome Theory

Johannsen Coins the Terms “Gene,” “Genotype,” and “Phenotype”