One Gene One Polypeptide

There are many steps between genotype and pheno-type. Genes cannot, all by themselves, directly produce a phenotypic result, such as a particular eye color, a specific seed shape, or a cleft chin, any more than a compact disk can play a symphony without the help of a CD player.

Ricinus communis, the Castor Bean Plant

This brightly colored plant, grown in the Tropics as an ornamental, produces ricin, a lethal toxin that inhibits protein synthesis at the ribosome.

Ricinus communis, the Castor Bean Plant

This brightly colored plant, grown in the Tropics as an ornamental, produces ricin, a lethal toxin that inhibits protein synthesis at the ribosome.

One Gene One Polypeptide

The first historical step in relating genes to phenotypes was to define phenotypes in molecular terms. The molecular basis of phenotypes was actually discovered before the discovery that DNA was the genetic material. Scientists had studied the chemical differences between individuals carrying wild-type and mutant alleles in organisms as diverse as humans and bread molds. They found that the major phe-notypic differences were the result of differences in specific proteins.

In the 1940s, a series of experiments by George W. Beadle and Edward L. Tatum at Stanford University showed that when an altered gene resulted in an altered phenotype, that altered phenotype was always associated with an altered enzyme. This finding was critically important in defining the phenotype in chemical terms.

The roles of enzymes in biochemistry were being described at this time, and it occurred to Beadle and Tatum that the expression of a gene as phenotype could occur through an enzyme. They experimented with the bread mold Neu-rospora crassa. The nuclei in the body of this mold are haploid (n), as are its reproductive spores. (This fact is important because it means that even recessive mutant alleles are easy to detect in experiments.) Beadle and Tatum grew Neurospora on a minimal nutritional medium containing sucrose, minerals, and a vitamin. Using this medium, the enzymes of wild-type Neurospora could catalyze the metabolic reactions needed to make all the chemical constituents of their cells, including proteins. These wild-type strains are called pro-totrophs ("original eaters").

Beadle and Tatum treated wild-type Neurospora with X rays, which act as a mutagen (something known to cause mutations). When they examined the treated molds, they found some mutant strains could no longer grow on the minimal medium, but needed to be supplied with additional nutrients. The scientists hypothesized that these aux-otrophs ("increased eaters") must have suffered mutations in genes that code for the enzymes used to synthesize the nutrients they now needed to obtain from their environment. For each auxotrophic strain, Beadle and Tatum were able to find a single compound that, when added to the minimal medium, supported the growth of that strain. This result suggested that mutations have simple effects, and that each mutation causes a defect in only one enzyme in a metabolic pathway described as the one-gene, one-enzyme hypothesis (Figure 12.1).

One group of auxotrophs, for example, could grow only if the minimal medium was supplemented with the amino acid arginine. (Wild-type Neurospora makes its own arginine.) These mutant strains were designated arg mutants. Beadle and Tatum found several different arg mutant strains. They proposed two alternative hypotheses to explain why these different genetic strains had the same phenotype:

► The different arg mutants could have mutations in the same gene, as in the case of the different eye color alleles of fruit flies. In this case, the gene might code for an enzyme involved in arginine synthesis.

► The different arg mutants could have mutations in different genes, each coding for a separate function that leads to argi-nine production. These independent functions might be different enzymes along the same biochemical pathway.

Some of the arg mutant strains fell into each of the two categories. Genetic crosses showed that some of the mutations were at the same chromosomal locus, and so were different alleles of the same gene. Other mutations were at different loci, or on different chromosomes, and so were not alleles of the same gene. Beadle and Tatum concluded that these different genes participated in governing a single biosynthetic pathway—in this case, the pathway leading to arginine synthesis (see the Conclusion in Figure 12.1).

By growing different arg mutants in the presence of various compounds suspected to be intermediates in the synthetic metabolic pathway for arginine, Beadle and Tatum were able to classify each mutation as affecting one enzyme or another, and to order the compounds along the pathway. Then they broke open the wild-type and mutant cells and examined them for enzyme activities. The results confirmed their hypothesis: Each mutant strain was indeed missing a single active enzyme in the pathway.

The gene-enzyme connection had been proposed 40 years earlier in 1908 by the Scottish physician Archibald Garrod, who studied the inherited human disease alkaptonuria. He linked the biochemical phenotype of the disease to an abnormal gene and a missing enzyme. Today we know of hundreds of examples of such hereditary diseases, which we will return to in Chapter 17.

The gene-enzyme relationship has undergone several modifications in light of our current knowledge of molecular biology. Many enzymes are composed of more than one polypeptide chain, or subunit (that is, they have a quaternary structure). In this case, each polypeptide chain is specified by its own separate gene. Thus, it is more correct to speak of a one-gene, one-polypeptide relationship: The function of a gene is to control the production of a single, specific polypeptide.

Much later, it was discovered that some genes code for forms of RNA that do not become translated into polypep-tides, and that still other genes are involved in controlling which other DNA sequences are expressed. While these discoveries have supplanted the idea that all genes code for proteins, they did not invalidate the relationship between genes and polypeptides. But how does this relationship work—that is, how is the information encoded in DNA used to specify a particular polypeptide?

Was this article helpful?

0 0
Addiction To Nutrition

Addiction To Nutrition

Get All The Support And Guidance You Need To Be A Success At Beating Addictions With Nutrition. This Book Is One Of The Most Valuable Resources In The World When It Comes To A Definitive Guide To Unchain Addiction The Smarter And Healthy Way.

Get My Free Ebook


Post a comment