Is the one gene, one enzyme hypothesis correct?

Beadle and Tatum’s experiments are important not only for their conceptual advances in understanding genes, but also because they demonstrate the utility of screening for genetic mutants to investigate a biological process — this is called genetic analysis.

Beadle and Tatum’s results were useful to investigate biological processes, specifically the metabolic pathways that produce amino acids. For example, Srb and Horowitz (1944) tested the ability of the amino acids to rescue auxotrophic strains. They added one of each of the amino acids to minimal medium and recorded which of these restored growth to independent mutants.

Watch the video below, BIOL 183: Beadle & Tatum’s One-Gene-One-Enzyme hypothesis, by Susan Bush (2020) at Metropolitan State University on YouTube, which explains the one – gene – one – enzyme hypothesis.

Figure 7.3.1 A Simplified Version of the Arg Biosynthetic Pathway, Showing Citrulline (Cit) and Ornithine (Orn) as Intermediates in Arg Metabolism. These chemical reactions depend on enzymes represented here as the products of three different genes.

A convenient example is arginine. If the progeny of a mutagenized spore could grow on minimal medium only when it was supplemented with arginine (Arg), then the auxotroph must bear a mutation in the Arg biosynthetic pathway and was called an “arginineless” strain (arg-).

Synthesis of even a relatively simple molecule such as arginine, requires many steps — each with a different enzyme. Each enzyme works sequentially on a different intermediate in the pathway (Figure 7.3.1). For arginine (Arg), two of the biochemical intermediates are ornithine (Orn) and citrulline (Cit). Thus, mutation of any one of the enzymes in this pathway could turn Neurospora into an Arg auxotroph (arg-). Srb and Horowitz extended their analysis of Arg auxotrophs by testing the intermediates of amino acid biosynthesis for the ability to restore growth of the mutants (Figure 7.3.2).

Figure 7.3.2 Testing Different Arg Auxotrophs for Their Ability to Grow on Media Supplemented with Intermediates in the Arg Biosynthetic Pathway

They found that only Arg could rescue all the Arg auxotrophs, while either Arg or Cit could rescue some (Table 7.3.1). Based on these results, they deduced the location of each mutation in the Arg biochemical pathway, (i.e., which gene was responsible for the metabolism of which intermediate).

Table 7.3.1 Ability of auxotrophic mutants of each of the three enzymes of the Arg biosynthetic pathways to grow on minimal medium (MM) supplemented with Arg or either of its precursors, Orn and Cit. Gene names refer to the labels used in Figure 7.3.1.Mutants InMM + OrnMM + CitMM + Arggene AYesYesYesgene BNoYesYesgene CNoNoYes

The video below, Gene Interactions P1, by Michelle Stieber (2014) on YouTube, discusses gene interactions and related biochemical pathways.

Media Attributions

References

Bush, S. (2020, April 16). BIOL 183: Beadle & Tatum’s one-gene-one-enzyme hypothesis (video file). YouTube. https://www.youtube.com/watch?v=4nXX2djQVvI

Deyholos, M. (2017). Figures: 4. A simplified version of the Arg biosynthetic pathway… and 5. Testing different Arg auxotrophs for their ability to grow…(digital image). In Locke, J., Harrington, M., Canham, L. and Min Ku Kang (Eds.), Open Genetics Lectures, Fall 2017 (Chapter 3, p. 3). Dataverse/ BCcampus. http://solr.bccampus.ca:8001/bcc/file/7a7b00f9-fb56-4c49-81a9-cfa3ad80e6d8/1/OpenGeneticsLectures_Fall2017.pdf

Srb, A. M. & Horowitz N. H. (1944). The ornithine cycle in Neurospora and its genetic control. Journal of Biological Chemistry, 154, 129-139. https://doi.org/10.1016/S0021-9258(18)71951-0

Stieber, M. (2014, April 12). Gene interactions P1 (video file). YouTube. https://www.youtube.com/watch?v=Fv7UtsPfF-A

The phrase "one gene, one protein" is inaccurate, as shown by the example of haemoglobin: this protein contains prosthetic haem groups which are not made by the activity of any gene, therefore genes alone cannot make every protein. "one gene, one enzyme" is also incorrect, because some genes code for proteins such as collagen or elastin, which have a structural role in the body rather than as catalysts in metabolism, so they are not enzymes.
The correct term is "one gene, one polypeptide" as the sequence of codons on any strand of DNA can only code for the assembly of a polypeptide chain with one possible arrangement of amino acid residues following transcription and translation.

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  • National Center for Biotechnology Information - PubMed Central - The centenary of the one-gene one-enzyme hypothesis

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Key People:George Wells Beadle Edward L. Tatum...(Show more)Related Topics:genetics enzyme gene...(Show more)

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one gene–one enzyme hypothesis, idea advanced in the early 1940s that each gene controls the synthesis or activity of a single enzyme. The concept, which united the fields of genetics and biochemistry, was proposed by American geneticist George Wells Beadle and American biochemist Edward L. Tatum, who conducted their studies in the mold Neurospora crassa. Their experiments involved first exposing the mold to mutation-inducing X-rays and then culturing it in a minimal growth medium that contained only the basic nutrients that the wild-type, or nonmutated, strain of mold needed to survive. They found that the mutant strains of mold required the addition of specific amino acids to the minimal medium in order to grow. Using this information, the researchers were able to associate mutations in specific genes to the disruption of individual enzymes in the metabolic pathways that normally produced the missing amino acids. This discovery won Beadle and Tatum the 1958 Nobel Prize for Physiology or Medicine (shared with American geneticist Joshua Lederberg).

Although the hypothesis was amply verified in principle, it has undergone considerable sophistication since the 1940s. Today it is known that not all genes encode an enzyme and that some enzymes are made up of several short polypeptides encoded by two or more genes.

Why is the one gene, one enzyme hypothesis is not entirely accurate?

"one gene, one enzyme" is also incorrect, because some genes code for proteins such as collagen or elastin, which have a structural role in the body rather than as catalysts in metabolism, so they are not enzymes.

Why is the one gene, one enzyme hypothesis important?

' In actuality they proved to be the opening gun in what became molecular genetics and all the developments that have followed from that." The development of the one gene–one enzyme hypothesis is often considered the first significant result in what came to be called molecular biology.

Why was the one gene, one enzyme hypothesis changed?

Beadle and Tatum's one gene-one enzyme hypothesis has been modified since one gene can code for multiple proteins, and all proteins are not enzymes. We also know that multiple polypeptides constitute the enzymes. Thus, to make the hypothesis more accurate it has been modified to "one gene-one polypeptide."

Why is the one gene one protein hypothesis?

They reasoned that each mutation must inactivate the enzyme (protein) needed to synthesize the nutrient. Thus, one gene carries the directions for making one protein.