Biochemical genetics is the combination of genetic analysis with biochemistry. It is now known that mutations can be introduced into genes and will change the primary structure of the encoded protein. In humans, these changes can affect enzyme activities or the function of structural proteins, resulting in diseases [local] or inborn errors in metabolism. These mutations can also have nonserious consequences and result in non-lethal changes such as different eye color.

Biochemists have learned to take advantage of mutants to learn about the inner workings of the cell. Rather than studying the inheritance of visible traits like eye color, biochemists have introduced high rates of mutations into microorganisms and then screened for loss of function. For example, many organisms are able to grow in media containing some simple mineral salts and a carbohydrate. After mutagenesis, it is possible to screen for mutants that require the addition of uracil to the medium. These organisms are different from the normal ('wild type') organisms in that they have lost the ability to produce the uracil necessary for RNA production and are termed auxotrophs. These auxotrophs have lost an enzyme in the pathway of uracil biosynthesis and often excrete the substrate of the defective enzyme into the medium. Different mutants may be blocked in different steps of the uracil biosynthetic pathway and may secrete different intermediate metabolites into the medium. The secreted intermediate from a mutant blocked at an enzyme late in the pathway may permit growth of a mutant blocked earlier in the pathway, but not vice-versa. This ability to rescue a mutant by feeding a metabolite following the blockage is called complementation [local]. By analyzing the excreted metabolites and the patterns of complementation in a number of mutants, it is possible to deduce a biosynthetic pathway.

Biochemical genetics was first used by Beadle and Tatum [local] to study catabolic pathways in bread mold. They created auxotrophs and analyzed them to determine the catabolic pathways for that organism. However, these experiments were of great fundamental importance because they demonstrated that individual biochemical reactions are catalyzed by individual enzymes which are coded by individual genes [local]. Their work resulted in the 'one gene-one enzyme [local]' hypothesis and is fundamental for much of modern biology.