Thomas Hunt Morgan

The discovery of more mutated genes allowed Morgan's group to explore how genes are arranged on the chromosome, and to discover an exception to one of Mendel's laws of inheritance. Mendel had proposed the Law of Independent Assortment, stating that the alternative forms of different traits (such as round versus wrinkled pea seeds and short versus tall plant height) separate and recombine independently of each other, so that, for instance, obtaining a wrinkled tall plant is just as likely as obtaining a wrinkled short plant.

Morgan found this was not always true. Rather, certain combinations of alleles are very unlikely to be separated from each other, a fact he attributed to co-inheritance of the two alleles on the same chromosome. While alleles on separate chromosomes assort independently, as Mendel predicted, those on the same chromosome travel together unless separated.

To explore this, Morgan crossed a red-eyed fly with normal-length wings with a purple-eyed fly with stubby wings. After two generations, Mendel's laws predicted that all possible combinations of eye color and wing length should be equally likely. Instead, Morgan found that most flies had the original trait combinations, while red-eyed, stubby-winged flies were rare, as were purple-eyed, normal-winged flies. He concluded that the genes for wing length and purple eye color were on the same chromosome. Like passengers traveling on the same ship, once the particular alleles were together, they tended to stay linked. (Note that the purple eye-color gene is not the same one as the red-white eye-color gene he discovered previously, and is not on the X chromosome.)

However, Morgan noted specific allele combinations didn't always stay together: There were a few flies whose stubby-wing allele and purple-eye allele had become separated from each other. This led Morgan to propose that chromosomes sometimes exchange segments, allowing their passengers to change vessels, so to speak. This phenomenon is known as crossing over, and was later conclusively demonstrated in maize by Barbara McClintock.

Crossing over is now known to occur only during meiosis, the chromosome division that leads to formation of eggs and sperm. During meioisis, homologous chromosomes originally donated from the mother and father pair up for an extended period. In this period, called synapsis, the maternal and paternal chromosomes randomly exchange several segments, resulting in a pair of chromosomes with a mix of maternally derived and paternally derived alleles. These then separate to form the eggs and sperm.

Morgan's student Sturtevant reasoned that the likelihood of two alleles becoming separated during crossing over was proportional to the distance between them. In other words, the closer they are, the more likely they will stay together, and the further apart they are, the more likely they will separate. If A, B, and C are on the same chromosome, and A stays with B more often than it stays with C, then the distance from A to B is shorter than the distance from A to C. In this way, the relative distances of genes can be determined, providing a "linkage map" of the chromosomes. The unit of relative distance is called the morgan, in honor of Morgan himself. Calvin Bridges later devised a method to determine the absolute distance between genes, relying on the distinct banding patterns seen in Drosophila chromosomes in the larval stage.