Two genes, chromosomes and linkage

A dihybrid cross follows two traits at once. Mendel crossed plants with round, yellow seeds (RRYY) and wrinkled, green seeds (rryy).

• F₁: all round and yellow, RrYy.
• An RrYy plant makes four kinds of gametes in equal numbers: RY, Ry, rY, ry.
• Combining these in a 4 × 4 Punnett square gives an F₂ of 9 round yellow : 3 round green : 3 wrinkled yellow : 1 wrinkled green.

Notice that each trait on its own still gives 3 : 1 (12 round : 4 wrinkled). This led to Mendel's third law, the Law of Independent Assortment: when two pairs of traits are combined in a hybrid, the segregation of one pair is independent of the other. A shortcut follows: multiply the separate chances. For example, the chance of being 'tall' (3/4) and 'green' (1/2) together is 3/4 × 1/2 = 3/8.

Mendel published in 1865, but his work was ignored for 35 years. In 1900, three scientists, de Vries, Correns and von Tschermak, independently rediscovered his results. By then, microscopes showed chromosomes moving during cell division.

Sutton and Boveri noticed that chromosomes behave just like Mendel's factors: they come in pairs, the pairs separate at meiosis, and different pairs separate independently. They proposed the chromosomal theory of inheritance: genes are carried on chromosomes. Thomas Hunt Morgan proved it with the fruit fly Drosophila melanogaster, which is ideal for genetics: it breeds quickly, has many offspring, and has clearly visible variations.

Morgan found that some genes do not assort independently. Genes on the same chromosome tend to be inherited together: they are linked. In such crosses, the parental combinations appear far more often than the new ones.

New combinations (recombinants) still appear, because during meiosis, paired chromosomes can exchange pieces (crossing over). The closer two genes are on a chromosome, the less often this separates them. Morgan found that the genes for white eyes and yellow body were tightly linked (only 1.3% recombination), while the genes for white eyes and miniature wings were much less so (37.2%). His student Alfred Sturtevant used these recombination frequencies as a measure of distance, and drew the first maps of genes on chromosomes.