One gene–one enzyme hypothesis

Source: Wikipedia, the free encyclopedia.

The one gene–one enzyme hypothesis is the idea that

oversimplification. Even the subsequent reformulation of the "one gene–one polypeptide" hypothesis is now considered too simple to describe the relationship between genes and proteins.[5]

Origin

Tatum's 1958 Nobel prize on the monument at the American Museum of Natural History in New York City
.

Although some instances of

Caltech laboratory of Thomas Hunt Morgan. In the mid-1930s they found that genes affecting eye color appeared to be serially dependent, and that the normal red eyes of Drosophila were the result of pigments that went through a series of transformations; different eye color gene mutations disrupted the transformations at a different points in the series. Thus, Beadle reasoned that each gene was responsible for an enzyme acting in the metabolic pathway of pigment synthesis. However, because it was a relatively superficial pathway rather than one shared widely by diverse organisms, little was known about the biochemical details of fruit fly eye pigment metabolism. Studying that pathway in more detail required isolating pigments from the eyes of flies, an extremely tedious process.[6]

After moving to

metabolites were synthesized in several metabolic pathways.[7] The obvious inference from these experiments was that each gene mutation affects the activity of a single enzyme. This led directly to the one gene–one enzyme hypothesis, which, with certain qualifications and refinements, has remained essentially valid to the present day. As recalled by Horowitz et al.,[8] the work of Beadle and Tatum also demonstrated that genes have an essential role in biosyntheses. At the time of the experiments (1941), non-geneticists still generally believed that genes governed only trivial biological traits, such as eye color, and bristle arrangement in fruit flies, while basic biochemistry was determined in the cytoplasm by unknown processes. Also, many respected geneticists thought that gene action was far too complicated to be resolved by any simple experiment. Thus Beadle and Tatum brought about a fundamental revolution in our understanding of genetics, for which they were awarded a Nobel Prize in Physiology or Medicine
in 1958.

The nutritional mutants of Neurospora also proved to have practical applications; in one of the early, if indirect, examples of

military funding of science in the biological sciences, Beadle garnered additional research funding (from the Rockefeller Foundation and an association of manufacturers of military rations) to develop strains that could be used to assay the nutrient content of foodstuffs, to ensure adequate nutrition for troops in World War II.[9]

The hypothesis and alternative interpretations

In their first Neurospora paper, published in the November 15, 1941, edition of the

nucleoproteins (although the Avery–MacLeod–McCarty experiment and related work was beginning to cast doubt on that idea). However, the proposed connection between a single gene and a single protein enzyme outlived the protein theory of gene structure. In a 1948 paper, Norman Horowitz named the concept the "one gene–one enzyme hypothesis".[2]

Although influential, the one gene–one enzyme hypothesis was not unchallenged. Among others, Max Delbrück was skeptical only a single enzyme was actually involved at each step along metabolic pathways. For many who did accept the results, it strengthened the link between genes and enzymes, so that some biochemists thought that genes were enzymes; this was consistent with other work, such as studies of the reproduction of tobacco mosaic virus (which was known to have heritable variations and which followed the same pattern of autocatalysis as many enzymatic reactions) and the crystallization of that virus as an apparently pure protein. At the start of the 1950s, the Neurospora findings were widely admired, but the prevailing view in 1951 was that the conclusion Beadle had drawn from them was a vast oversimplification.[8] Beadle wrote in 1966, that after reading the 1951 Cold Spring Harbor Symposium on Genes and Mutations, he had the impression that supporters of the one gene–one enzyme hypothesis “could be counted on the fingers of one hand with a couple of fingers left over.”[10] By the early 1950s, most biochemists and geneticists considered DNA the most likely candidate for physical basis of the gene, and the one gene–one enzyme hypothesis was reinterpreted accordingly.[11]

One gene–one polypeptide

In attributing an instructional role to genes, Beadle and Tatum implicitly accorded genes an informational capability. This insight provided the foundation for the concept of a genetic code. However, it was not until the experiments were performed showing that DNA was the genetic material, that proteins consist of a defined linear sequence of amino acids, and that DNA structure contained a linear sequence of base pairs, was there a clear basis for solving the genetic code.

By the early 1950s, advances in biochemical genetics—spurred in part by the original hypothesis—made the one gene–one enzyme hypothesis seem very unlikely (at least in its original form). Beginning in 1957,

multimeric protein, leading to a "one gene–one polypeptide" hypothesis instead.[12] According to geneticist Rowland H. Davis, "By 1958 – indeed, even by 1948 – one gene, one enzyme was no longer a hypothesis to be resolutely defended; it was simply the name of a research program."[13]

Presently, the one gene–one polypeptide perspective cannot account for the various spliced versions in many eukaryote organisms which use a

Phillip Sharp and Richard J. Roberts[14]

Possible anticipation of Beadle and Tatum's results

Historian Jan Sapp has studied the controversy in regard to German geneticist Franz Moewus who, as some leading geneticists of the 1940s and 50s argued, generated similar results before Beadle and Tatum's celebrated 1941 work.[15] Working on the algae Chlamydomonas, Moewus published, in the 1930s, results that showed that different genes were responsible for different enzymatic reactions in the production of hormones that controlled the organism's reproduction. However, as Sapp skillfully details, those results were challenged by others who found the data 'too good to be true' statistically, and the results could not be replicated.

See also

References

  • ISBN 0-300-07608-8
    .
  • Kay LE (1993). The Molecular Vision of Life: Caltech, The Rockefeller Foundation, and the Rise of the New Biology. New York:
    ISBN 0-19-511143-5
    .
  • Morange M (1998). A History of Molecular Biology. Cobb M (trans.). Cambridge:
    ISBN 0-674-39855-6
    .
  1. ^ a b Beadle GW, Tatum EL (15 November 1941). "Genetic Control of Biochemical Reactions in Neurospora" (PDF).
    PMID 16588492
    .
  2. ^
    PMID 18207813
    .
  3. PMID 15020400
    .
  4. ^ Morange, p. 21
  5. ^ Bussard AE (2005). "A scientific revolution? The prion anomaly may challenge the central dogma of molecular biology".
    PMID 16065057
    .
  6. ^ Morange, pp. 21-24
  7. ^ Fruton, pp. 432-434
  8. ^
    PMID 8722756
    .
  9. ^ Kay, pp. 204-205.
  10. ^ Beadle, G. W. (1966) "Biochemical genetics: some recollections", pp. 23-32 in Phage and the Origins of Molecular Biology, edited by J. Cairns, G. S. Stent and J. D. Watson. Cold Spring Harbor Symposia, Cold Spring Harbor Laboratory of Quantitative Biology, NY. ASIN: B005F08IQ8
  11. ^ Morange, pp. 27-28
  12. ISBN 978-0-87969-688-7
  13. S2CID 11263056
    .
  14. ^ Chow, Louise T., Richard E. Gelinas, Thomas R. Broker, and Richard J. Roberts. "An amazing sequence arrangement at the 5' ends of adenovirus 2 messenger RNA." Cell 12, no. 1 (September 1977): 1-8.
  15. ^ Jan Sapp (1990), Where the Truth Lies: Franz Moewus and the Origins of Molecular biology, New York: Oxford University Press.

Further reading

Retrieved from "https://en.wikipedia.org/w/index.php?title=One_gene–one_enzyme_hypothesis&oldid=1198911388"