Alfred Sturtevant

Alfred Henry Sturtevant (November 21, 1891–April 5, 1970) was an American geneticist. Sturtevant constructed the first genetic map of a chromosome in 1913. Throughout his career he worked on the organism Drosophila melanogaster with Thomas Hunt Morgan. By watching the development of flies in which the earliest cell division produced two different genomes, he measured the embryonic distance between organs in a unit which is called the sturt in his honor. In 1967, Sturtevant received the National Medal of Science.

Biography
Alfred Henry Sturtevant was born in Jacksonville, Illinois, United States on November 21, 1891, the youngest of Alfred Henry and Harriet Sturtevant's six children. His grandfather Julian M. Sturtevant, a Yale University graduate, founded Illinois College where his father taught mathematics.

When Sturtevant was seven years old, his father quit his teaching job and moved the family to Alabama to pursue farming. Sturtevant attended a one room schoolhouse until entering high school in Mobile. In 1908, he enrolled at Columbia University. During this time, he lived with his older brother Edgar who taught nearby. Edgar taught Alfred about scholarship and research.

As a child, Sturtevant had created pedigrees of his father’s horses. While in college, he read about Mendelism, which piqued Sturtevant’s interest because it could explain the traits expressed in the horse pedigrees. He further pursued his interest in genetics under Thomas Hunt Morgan, who encouraged him to publish a paper of his pedigrees shown through Mendelian genetics. In 1914, Sturtevent completed his doctoral work under Morgan as well.

After earning his doctorate, Sturtevant stayed at Columbia as a research investigator for the Carnegie Institution of Washington. He joined Morgan's research team in the "fly room", in which huge advances were being made in the study of genetics through studies of the fruit fly Drosophila. In 1922, he married Phoebe Curtis Reed, and the couple subsequently had three children.

In 1928, the Sturtevant moved to Pasadena to work at the California Institute of Technology, where he became a Professor of Genetics and remained for the rest of his career, except for one year when he was invited to teach in Europe. He taught an undergraduate course in genetics at Caltech and wrote a textbook with George Beadle. He became the leader of a new genetics research group at Caltech, whose members included George W. Beadle, Theodosius Dobzhansky, Sterling Emerson, and Jack Schultz. In 1967, he received the National Medal of Science for his longtime work on the genetics of Drosophila and other organisms.

Sturtevant was interested in taxonomy as well as genetics. He loved solving all kinds of puzzles and saw genetics as a puzzle for him to decipher. He was widely read, interested in politics, newspapers, scientific journals across many subjects and crossword puzzles. He had an impressive memory and composed and edited papers in his head before writing them down from memory. He enjoyed a long and prosperous career in genetics until his death on April 5, 1970.

Historical Context
Sturtevant accomplished most of his work between 1910 and World War II. These years saw both World War I and the Great Depression. Prior to WWII, universities and research programs operated under private donations; the federal government was not very involved in the funding of scientific research. Much research prior to WWII concerned the chemical nature of heredity. WWII changed the course of science. Focus was shifted away from biology and genetics to nuclear chemistry and physics. During and after WWII, the government became the key financial backer of scientific research, in the hopes that funding basic research would lead to technological advances. In this same timeframe, Sturtevant was an outspoken opponent of eugenics and was interested in the effects of the atomic bomb on human populations, due to his previous research on lethal genes. He warned the public of possible harmful genetic effects of nuclear fallout despite supposedly low levels of ionizing radiation.

Genetic/Hereditary Research Prior to Sturtevant
In 1865, Gregor Mendel published a paper entitled “Experiments in Plant Hybridization,” in which he proposed the principles of heredity. This paper introduced the concept of dominant and recessive genes to explain how a characteristic can be repressed in one generation but appear in the next generation. Mendel also assumed that all hereditary factors worked independently of one another, which he explained in his law of independent assortment. Mendel’s paper did not achieve much acclaim and was largely forgotten until 1900.

1865 to 1900 saw a time of theory formulation in the field of heredity/genetics. In 1883, Wilhelm Roux argued that the linear structure of chromosomes has an impact of making sure daughter cells get equal amounts of chromosomal material. This was the beginning of the chromosome theory; Roux viewed his findings as argument that chromosomes contain units of heredity. During this timeframe, Hugo de Vries put forth a theory that persistent hereditary units are passed through generations and that each “unit” deals with a specific characteristic and the units can combine in different ways in the offspring.

From 1900 – 1909, anomalous data began to accumulate. Gene linkage was first reported by Carl Correns in 1900, contradicting Mendel’s law of independent assortment. Thomas Hunt Morgan was the first to provide a working hypothesis for these exceptions. He postulated that genes that remained together while being passed from generation to generation must be located on the same chromosome.

Sturtevant’s Work and its Impact/Importance
Sturtevant’s most notable discoveries include the principle of genetic mapping, the first reparable gene defect, the principle of underlying fate mapping, the phenomena of unequal crossing-over, and position effect. His main contributions to science include his analysis of genetic “linkage groups,” which became classical method of chromosome mapping that we still use today. In 1913, he determined that genes were arranged on chromosomes in a linear fashion, like beads on a necklace. He also showed that the gene for any specific trait was in a fixed location (locus).

His work between 1915 and 1928, Sturtevant determined that genes of Drosophila are arranged in linear order. In 1920, he published a set of three papers under the title “Genetic Studies on Drosophila simulans,” which “proved that two closely related species had newly recurring mutations that were allelic and thus probably identical” (Provine 2). His work also helped to determine genetic role in sexual selection and development and displayed the importance of chromosomal crossing-over in mutations.

One of Sturtevant’s principle contributions was his introduction to the concept that the frequency of crossing-over between two genes could help determine their proximity on a linear genetic map. His experiments determined that the frequency of double crossing over can be used to deduce gene order. He demonstrated this concept by constructing crosses of three segregating genes, called "three-factor crosses". He found that using three genes as opposed to two provided most accurate information about gene order on chromosome. With this system, Sturtevant discovered that double crossing-over occurs at frequency of equal to or less than product of two single crossing over frequencies. He also surmised that unequal crossing-over was possibly a main force of evolution. "Sturtevant... elaborated on these ideas by incorporating the conception of linear arrangement and by constructing the first chromosome map. Double crossing over and interference were deductions that arose from this result" (Sturtevant, An Introduction to Genetics p.361).

Sturtevant's work on the Drosophila genome enabled geneticists to further map chromosomes of higher organisms, including human beings. His former Caltech research partner G.W. Beadle claimed that modern biochemical genetics stems directly from Sturtevant’s work.

Other Noteworthy contributions of Sturtevant
•	He discovered unequal crossing over – one chromosome breaks so that it yields two crossovers
 * Did a cross of certain eye/wing characteristics produced only 6 phenotypes when it should have produced 8. This showed that 3 of the phenotypes (and hence genotypes) were linked – to interpret results, you must assume that the genes are arranged on the chromosome in a specific order. The cross test tells us the sequence of the genes.
 * Theorized that consistency of crossover values and the constant order of genes on a chromosome means that a gene occupies a fixed position in a chromosome, and the allele has the corresponding position in the homologous chromosome. The intervals between adjacent loci are crossover regions and are numbered from left to right. A chromosome map, therefore, is a chart that illustrates the spacing of the genes on a chromosome. He defined a map unit as a distance that will give (on average at standard conditions) one crossover per 100 gametes.
 * Sturtevant was a supported of the chromosome theory of inheritance: "several explanations of linkage have been advanced in the past, but it is now quite clear that the correct interpretation is that genes are linked because they are carried on the same chromosome". (Sturtevant, An Introduction to Genetics p.66)
 * Discovered that single chromatids do not cross over.
 * Invented fate mapping, which reveals how certain cells develop and most importantly where they end up in the body.
 * [Sturtevant] suddenly realized that the variations in strength of linkage, already attributed by Morgan to differences in the spatial separation of genes, offered the possibility of determining sequences in the linear dimension of a chromosome. I went home and spent most of the night (to the neglect of my undergraduate homework) in producing the first chromosome map, which included the sex linked genes y, w, v, m, and r, in the order and approximately the same relative spacing that they still appear on the standard maps" (Sturtevant, A History of Genetics p.47).
 * "By 1915 the work with Drosophila had progressed to the point where the group at Columbia was ready to try to interpret the whole field of Mendelism in terms of the chromosome theory. The resulting book, The Mechanism of Mendelian Heredity (Morgan, Sturtevant, Muller and Bridges, 1915), is a milestone in the history of the subject". (Sturtevant, A History of Genetics p48-49).
 * There was still much exciting and fundamental work to be done with Drosophila…but it had become a question of how the chromosome mechanism worked, not of whether it could be demonstrated to be the true mechanism” (Sturtevant, A History of Genetics 49)

•	Morgan proposed (in 1911, after Sturtevant’s work/invention) that linkage is due to genes being on same chromosome (alleles being on same pair of chromosomes) – closely linked genes closer on chromosome - “Here, then, in 1911, was the essence of the chromosome interpretation of the phenomena of inheritance” (Sturtevant, A History of Genetics 44)

•	Sturtevant’s most famous and revolutionary discovery, chromosome mapping, has many important uses in modern biology:

•	each chromosome has a banding pattern; numbered to help identify regions of a particular chromosome •	chromosome maps have allowed for the development of karyotypes/karyotyping

•	chromosome maps allows us to know where the gene for a particular trait is (ex – glaucoma on 1st chromosome – knowing location of gene allows for development of genetic tests

•	helpful in establishing genome testing

•	chromosome mapping details the position and spacing of “biochemical landmarks” (ex- genes)

•	modern geneticists still use Sturtevant’s technique of mapping & his same map unit: 1 map unit = 1% frequency of recombination

•	Mapping genes and linkage maps have important applications for medical screening. For example, the muscular dystrophy gene DS is linked by 10 map units to the S locus, coding for a specific antigen that can be detected immunologicaly. These genetic tools are also quite useful for indirect selection of desirable traits (for example, disease resistance), on the basis or linked markers in practical breeding. Maps are also used for evolutionary inferences among related species and for other fundamental research programs. The new field of genomics started with the gene mapping work of T. Morgan. (Quiros) “Using the molecular techniques developed by the children of Morgan, his scientific children, they identified an abnormal mutation in a gene encoding a protein that was quite well known called synuclein, and that has proved enormous[ly] helpful in out analysis of the mechanisms of Parkinson’s Disease” (Edelman 6).

•	discovered chromosome inversion: a segment of a chromosome is turned upside down and reattached to the chromosome

•	balanced inversion occurs if all of the genes normally present in the uninverted chromosome are still present in the inverted chromosome; if genes get lost or duplicated, inversion is unbalanced – this can cause birth defect

•	Sturtevant’s discovery of inversion is important because it explains the why/how of certain genetic defects and discovery of inversion allows for its presence to be tested for

•	Genetic tests exist today for some disorders caused by inversions

Key publications

 * The linear arrangement of six sex-linked factors in Drosophila, as shown by their mode of association. Journal of Experimental Zoology, 14: 43-59, 1913
 * The North American Species of Drosophila. Carnegie Institute of Washington, 1921.
 * A History of Genetics. Cold Spring Harbor Laboratory Press. Online Electronic Edition

Former Graduate Students
Edward B. Lewis