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PASS Scripta Varia 21 - Pontifical Academy of Sciences

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THE EVOLVING CONCEPT OF THE GENE<br />

the ‘one gene-one enzyme’ hypothesis, supporting the view that genes carried<br />

information related to the metabolic processes taking place inside the<br />

cells and more specifically, that each individual gene is responsible for the<br />

synthesis <strong>of</strong> a single enzyme. 17 Chemistry also had a role to play.Vernon Ingram<br />

showed that changes in two abnormal hemoglobins due to mutations<br />

were in each case confined to a single amino acid residue <strong>of</strong> the globin<br />

polypeptide. Since there could be no doubt that genes determine the amino<br />

acid residues <strong>of</strong> polypeptide chains, the expression ‘one gene-one enzyme’<br />

was modified to ‘one gene-one polypeptide’. 18<br />

The nature <strong>of</strong> the genetic material became even more tangible when Oswald<br />

Avery 19 and collaborators showed that the substance causing transformation<br />

in experiments that followed the protocols <strong>of</strong> Griffith’s was DNA.<br />

Unambiguous confirmation <strong>of</strong> the DNA theory <strong>of</strong> inheritance was obtained<br />

few years later by Alfred D. Hershey and Martha Chase. 20 The structure <strong>of</strong><br />

DNA proposed by Watson and Crick in 1953 gave the definite stroke to the<br />

instrumentalist view <strong>of</strong> the gene in favor <strong>of</strong> the realistic one, initiating the<br />

classical molecular gene concept. This states that a gene is a stretch <strong>of</strong> DNA that<br />

encodes a functional product, a single polypeptide chain or RNA molecule.<br />

Implicit in it is the idea that this genome unit performs one single function.<br />

At last, then, structure and function were blended in the same concept.<br />

The newly revealed structure <strong>of</strong> DNA also encouraged speculation<br />

about the still prevailing idea <strong>of</strong> the gene as a unity <strong>of</strong> function, mutation<br />

and recombination. Prior to 1955, several investigators had already obtained<br />

the first hints that the unit <strong>of</strong> function might not be indivisible, since not<br />

only more than one mutation could be mapped to the same gene but also<br />

intragenic recombination had been detected in D. melanogaster and the fungus<br />

Aspergillus nidulans <strong>21</strong> (see also references therein). Who most clearly confirmed<br />

this was Seymour Benzer. The so-called cis-trans complementation<br />

test led him to coin the word cistron to imply the unit <strong>of</strong> genetic function.<br />

17<br />

Beadle, G.W. and Tatum, E.L. Genetic control <strong>of</strong> biochemical reactions in Neurospora.<br />

Proc. Natl. Acad. Sci. 27: 499-506, 1941.<br />

18<br />

Dunn, L.C. Old and New in Genetics. Bull. New York Acad. Med. 40(5): 325-333,<br />

329, 1964.<br />

19<br />

Avery, O.T., MacLeod, C.M., and McCarty, M. Studies on the chemical nature <strong>of</strong> the<br />

substance inducing transformation <strong>of</strong> pneumococcal types. J. Exp. Med. 79: 137-158, 1944.<br />

20<br />

Hershey, A.D., and Chase, M. Independent functions <strong>of</strong> viral protein and nucleic<br />

acid in growth <strong>of</strong> bacteriophage. J. Gen. Physiol. 36, 39-56, 1952.<br />

<strong>21</strong><br />

Portin, P. The origin, development and present status <strong>of</strong> the concept <strong>of</strong> the gene:<br />

A short historical account <strong>of</strong> the discoveries. Current Genomics 1, 29-40, 2000.<br />

The Scientific Legacy <strong>of</strong> the 20 th Century<br />

201

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