You have all heard about the DNA double helix and genes. Many of you know that mutations occur randomly, that the DNA sequence is read by successive groups of three bases (the codons), that many genes encode enzymes, and that gene expression can be regulated.
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Classical papers in molecular genetics
Университет ЖеневыОб этом курсе
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Университет Женевы
Founded in 1559, the University of Geneva (UNIGE) is one of Europe's leading universities. Devoted to research, education and dialogue, the UNIGE shares the international calling of its host city, Geneva, a centre of international and multicultural activities with a venerable cosmopolitan tradition.
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Session 1
At the dawn of genetics, in the work of Mendel and Morgan, there was a complete void between the genes and the characters they determine.During the first week, we will discuss the relationship between genes and enzymes. We will start with the description of alkaptonuria by Garrod, in 1902, which he called a few years later an inborn error of metabolism. This was the first documented example of a human recessive trait, the first association of a human condition with Mendel’s principles and the first link between a gene and an enzyme. This work and that of Cuénot on mice fur color were essentially forgotten in the biology community in the following decades.After working with great difficulty on the enzymatic cascade that leads to the formation of the pigmented eye of fruit flies, Beadle and Tatum founded the field of biochemical genetics by isolating conditional mutants that affect the synthesis of vitamins and amino acids. This was first done with a mold, and then extended to bacteria. These experiments lead to the “one gene, one enzyme” hypothesis. While the hypothesis is now proven in many cases, the exceptions, including multigene enzymes, structural and enzymatic RNAs have expanded the concept rather than invalidating it.
Session 2
Most people believed that genes must be made of proteins because nucleic acids were considered too simple to carry genetic information. Avery worked all his life on Pneumococcus and bacterial pneumonia. Griffith showed that transformation of a non-virulent strain can be achieved in mice by coinjection of heat-killed virulent bacteria. Avery’s lab managed to obtain transformation in the test tube, but it took many years to establish a reliable assay and finally to purify the molecule responsible for this effect, which turned out to be DNA.
Session 3
The origin of mutations was a field of heavy discussions between proponents of Darwinism and those of Lamarckism. The major issue was to define an experimental approach that would unambiguously discriminate between mutations occurring at random and mutations caused by the selective agent used to reveal their existence. In the case of bacteria that became resistant to the lytic action of a bacteriophage, the hypotheses were labeled “mutation to immunity” versus “acquired immunity”. Luria and Delbrück realized that the variations observed in the number of resistant bacteria in different parallel cultures were intimately linked to the mutation hypothesis. This exceptional collaboration between a theoretical physicist and a bacteriologist is a perfect example of interdisciplinary work, while these two “enemy aliens” were working in the USA.
Session 4
When DNA was found to be the genetic material, it was not known how this molecule could carry information. The structure of DNA thus became of critical importance. The available X-ray images obtained by M. Wilkins and R. Franklin only yielded a rough picture, and even R. Franklin, who had the clearest diffraction data, could not decide whether the molecules contained two or three strands. Both Pauling and Watson and Crick used molecular models with known inter-nuclear distances (bond length) and bond angles to predict a structure. While the model of Pauling was hardly realistic, since it used the protonated form of the phosphate, the model proposed by Watson and Crick proposed that DNA consists of a pair of DNA strands. Furthermore, it indicated that any nucleotide sequence could be accommodated in the structure. The only central biological issue that was addressed in the first paper was replication, and the famous sentence was really nothing more than a priority claim. Much more biology was discussed in the second paper. It was assumed that base pairing is sufficient to account for the fidelity of replication. The importance of DNA polymerase in replication fidelity was first demonstrated by Speyer.
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Лучшие отзывы о курсе CLASSICAL PAPERS IN MOLECULAR GENETICS
Excellent course. The delivery of lecture notes was not easy to follow in the videos.
Amazing course! Even more interested in molecular genetics. Best professor!
Amazing course! Very well designed and delivered. It was specially delightful to have some historical context to the papers, as well as insight into the biography of the scientists themselves.
The professor was excellent and dedicated. I request the professor to take a course on fundamental papers in Biochemistry. Thank you professor Dominique!
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