The “scientific catastrophe” that made DNA boring - Chargaff versus the Tetranucleotide Hypothesis

Chargaff E, Vischer E, Doniger R, Green C, Misani F. The composition of the desoxypentose nucleic acids of thymus and spleen. J Biol Chem. 1949 Jan;177(1):405-16.
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DNA is now known as the primary molecule responsible for encoding genetic information. But scientists in the early 1900s considered DNA to be ‘idiotic’, unable to carry any information at all. It wasn’t until the 1940s that DNA even began to be considered as in an important biological chemical. This hold-up has been called a ‘scientific catastrophe’ (Glass 1965). So, what was this catastrophe, and how was it eventually rectified?
In the early 20th century, Russian scientist Phoebus Levene worked out the chemical makeup of DNA; a backbone made of sugar and phosphate, with bases attached (A, C, G or T). Throughout these experiments Levene, using crude methods, found that each base was present in about equal amounts (25% each). From this, he hypothesised that DNA was just a repeat of all four bases over and over again. This is called the tetranucleotide hypothesis, under which DNA was considered to be very simple and thus couldn’t code for any information.
The tetranucleotide hypothesis stood for over 30 years before Erwin Chargaff’s seminal work in 1949. He and his team showed, using some of the new chemical techniques available like paper chromatography and UV-Vis spectrometry, that each base was not present in equal amounts. This was strong evidence against the tetranucleotide hypothesis; finally ending the ‘scientific catastrophe’ and ensuring DNA could now be considered, at a chemical level, to have the complexity to code for life.
This had a massive impact on the early days of molecular genetics. Chargaff would discover, in contrast to the tetranucleotide hypothesis, that A and T were always in equal amounts, and G and C were always in equal amounts. Watson and Crick, of the DNA double helix fame, built upon Chargaff’s work when they suggested that the bases in DNA formed AT and GC complimentary pairs. The Hershey and Chase experiment only a few years later showed DNA could encode genetic information. This explosion of new discoveries about DNA finally showed to all of humanity the beauty and complexity of one of the most important molecules on the planet.
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References:
Chargaff E, Lipshitz R, Green C. Composition of the desoxypentose nucleic acids of four genera of sea-urchin. J Biol Chem. 1952;195(1):155-160.
Chargaff E, Vischer E, Doniger R, Green C, Misani F. The composition of the desoxypentose nucleic acids of thymus and spleen. J Biol Chem. 1949;177(1):405-416.
Hershey A, Chase M. Independent functions of viral protein and nucleic acid in growth of Bacteriophage. J Gen Physiol. 1952;36(1):39-56.
Watson J, Crick F. Molecular structure of nucleic acids: A structure for deoxyribose nucleic acid. Nature. 1953;171(4356):737-738.
Frixione E, Ruiz-Zamarripa L. The “scientific catastrophe” in nucleic acids research that boosted molecular biology. J Biol Chem. 2019;294(7):2249-2255.
Glass B. A century of biochemical genetics. Proc Am Philos Soc. 1965;109(4):227-236.
Hargittai I. The tetranucleotide hypothesis: a centennial. Struct Chem. 2009;20(5):753-756.
Lamm E, Harman O, Veigl S. Before Watson and Crick in 1953 came Friedrich Miescher in 1869. Genetics. 2020;215(2): 291-296.
Manchester K. Historical opinion: Erwin Chargaff and his “rules” for the base. Trends Biochem Sci. 2008;33(2):65-70.
Thomas N. The early history of spectroscopy. J Chem Educ. 1991;68(8):631.
Vischer E, Chargaff E. The separation and quantitative estimation of purines and pyrimidines in minute amounts. J Biol Chem. 1948;176(2):703-714.