In the 1930s, George Beadle and Boris Ephrussi discovered factors that affect eye colors in developing fruit flies. They did so while working at the California Institute of Technology in Pasadena, California. (1) They took optic discs (colored fuchsia in the image) from fruit fly larvae in the third instar stage of development. Had the flies not been manipulated, they would have developed into adults with vermilion eyes. (2) Beadle and Ephrussi transplanted the donor optic discs into the bodies of several types of larvae, including those that would develop with normal colored eyes (brick red), and those that would develop eyes with other shades of red, such as claret, carmine, peach, and ruby (grouped together and colored black in the image). (3a) When implanted into normal hosts that would develop brick red eyes, the transplanted optic disc developed into an eye that also was brick red. (3b) When implanted into abnormal hosts that would develop eyes of some other shade of red, the transplanted optic discs developed into eyes that were vermilion. Beadle and Ephrussi concluded that there was a factor, such as an enzyme or some other protein, produced outside of the optic disc that influenced the color of the eye that developed from the disc.

This illustration shows George Beadle and Edward Tatum's experiments with Neurospora crassa that indicated that single genes produce single enzymes. The pair conducted the experiments at Stanford University in Palo Alto, California. Enzymes are types of proteins that can catalyze reactions inside cells, reactions that produce a number of things, including nutrients that the cell needs. Neurospora crassa is a species of mold that grows on bread. In the early 1940s, Beadle and Tatum conducted an experiment to discover the abnormal genes in Neurospora mutants, which failed to produce specific nutrients needed to survive. (1) Beadle and Tatum used X-rays to cause mutations in the DNA of Neurospora, and then they grew the mutated Neurospora cells in glassware. (2) They grew several strains, represented in four groups of paired test tubes. For each group, Neurospora was grown in one of two types of growth media. One medium contained all the essential nutrients that the Neurospora needed to survive, which Beadle and Tatum called a complete medium. The second medium was a minimal medium and lacked nutrients that Neurospora needed to survive. If functioning normally and in the right conditions, however, Neurospora can produce these absent nutrients. (3) When Beadle and Tatum grew the mutated mold strains on both the complete and on the minimal media, all of the molds survived on the complete media, but not all of the molds survived on the minimal media (strain highlighted in yellow). (4) For the next step, the researchers added nutrients to the minimal media such that some glassware received an amino acid mixture (represented as colored squares) and other glassware received a vitamin mixture (represented as colored triangles) in an attempt to figure out which kind of nutrients the mutated molds needed. The researchers then took mold from the mutant mold strain that had survived on a complete medium and added that mold to the supplemented minimal media. They found that in some cases the mutated mold grew on media supplemented only with vitamins but not on media supplemented only with amino acids. (5) To discover which vitamins the mutant molds needed, Beadle and Tatum used several tubes with the minimal media, supplementing each one with a different vitamin, and then they attempted to grow the mutant mold in each tube. They found that different mutant strains of the mold grew only on media supplemented with different kinds of vitamins, for instance vitamin B6 for one strain, and vitamin B1 for another. In experiments not pictured, Beadle and Tatum found in step (4) that other strains of mutant mold grew on minimal media supplemented only with amino acids but not on minimal media supplemented only with vitamins. When they repeated step (5) on those strains and with specific kinds of amino acids in the different test tubes, they found that the some mutated mold strains grew on minimal media supplemented solely with one kind of amino acid, and others strains grew only on minimal media supplemented with other kinds of amino acids. For both the vitamins and amino acid cases, Beadle and Tatum concluded that the X-rays had mutated different genes in Neurospora, resulting in different mutant strains of Neurospora cells. In a cell of a given strain, the X-rays had changed the gene normally responsible for producing an enzyme that catalyzed a vitamin or an amino acid. As a result, the Neurospora cell could no longer produce that enzyme, and thus couldn't catalyze a specific nutrient.

Between 1934 and 1945, George Beadle developed a hypothesis that each gene within the chromosomes of organisms each produced one enzyme. Enzymes are types of proteins that can catalyze reactions inside cells, and the figure shows that each enzyme controls a stage in a series of biochemical reactions. The top box in this figure represents a normal process of enzyme production and biochemical reactions, and the bottom box shows how Beadle's experiments affected the normal biochemical process. In this figure, each box represents the borders of the cell, and the dashed lines inside the box represent the nucleus. In the normal cell depiction, three genes (represented as colored rectangles) in the nucleus influence the production of three corresponding enzymes (represented as colored squares). The collections of black circles, orange triangles, green squares, and purple circles represent organic molecules, which the enzymes affect through metabolic reactions. In the normal box, gene 3 somehow produces enzyme 3, which catalyzes a reaction in which the first two molecules combine to form a larger molecule. Enzyme 2 catalyzes the second step in the reaction in which the enzyme modifies the chemical composition of the molecule. Enzyme 3 catalyzes the third step in the reaction in which a carbon atom is added to the molecule. This figure also represents an abnormal process (bottommost box) of enzyme production and biochemical reactions. In the abnormal process, X-rays damaged gene 2, preventing the production of enzyme 2. As a result, neither the second nor the third steps of the chemical reaction can occur.

Y-chromosomes exist in the body cells of many kinds of male animals. Found in the nucleus of most living animal cells, the X and Y-chromosomes are condensed structures made of DNA wrapped around proteins called histones. The individual histones bunch into groups that the coiled DNA wraps around called a nucleosome, which are roughly 10 nano-meters (nm) across. The histones bunch together to form a helical fiber (30 nm) that spins into a supercoil (200 nm). During much of a cell's life, DNA exists in the 200 nm supercoil phase. But when DNA replicates itself, supercoils condense further into visible chromosomes with diameters of about 1400 nm. The X- and Y-chromosomes carry the genetic information that determines the sex of many types of animals. The Y-chromosome contains a gene called the sex-determining region Y, or the SRY gene in humans. If a fertilized egg, called a zygote, has the SRY gene, the zygote develops normally into an adult organism with male sex traits. Zygotes without the SRY gene develop to have female traits. Zygotes with Y-chromosomes but mutated SRY genes can develop into adult organisms that have female traits.

In 1935, George Beadle and Boris Ephrussi developed a technique to transplant optic discs between fruit fly larvae. They developed it while at the California Institute of Technology in Pasedena, California. Optic discs are tissues from which the adult eyes develop. Beadle and Ephrussi used their technique to study the development of the eye and eye pigment. (1) The experimenter dissects a donor larva, which is in the third instar stage of development, and removes the optic disc (colored red) with a micropipette. Because the antenna disc is attached to the optic disc, they are often removed and transplanted together. (2) The experimenter then implants the optic disc into a host larva, in the part of the host that will develop into an adult abdomen. As the host larva matures to adulthood, the implanted optic disc develops into an eye inside the body cavity of the adult. (3) The adult host has an eye within its body, which Beadle and Ephrussi found by dissecting the adult hosts. If the antenna disc was also transplanted, sometimes the resulting eye developed with an antenna attached.

Wilhelm Johannsen in Denmark first proposed the distinction between genotype and phenotype in the study of heredity in 1909. This distinction is between the hereditary dispositions of organisms (their genotypes) and the ways in which those dispositions manifest themselves in the physical characteristics of those organisms (their phenotypes). This distinction was an outgrowth of Johannsen's experiments concerning heritable variation in plants, and it influenced his pure line theory of heredity. While the meaning and significance of the genotype-phenotype distinction has been a topic of debate-among Johannsen's contemporaries, later biological theorists, and historians of science-many consider the distinction one of the conceptual pillars of twentieth century genetics. Moreover some have used it to characterize the relationships between studies of development, genetics, and evolution.