Classical papers in molecular genetics
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Classical papers in molecular genetics
University of Geneva
Об этом курсе
4.7
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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.
These concepts were proposed on the basis of astute genetic experiments, as well as often on biochemical results. The original articles were these concepts appeared are however not frequently part of the normal curriculum of biologists, biochemists and medical students.
This course proposes to read study and discuss a small selection of these classical papers, and to put these landmarks in their historical context. Most of the authors displayed interesting personal histories and many of their contributions go beyond not only the papers we will read but probably all their scientific papers.
Our understanding of the scientific process, of the philosophy underlying the process of scientific discovery, and on the integration of new concepts is not only important for the history of science but also for the mental development of creative science.
Программа курса: что вы изучите
1
Раздел
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.
7 видео (всего 107 мин.), 2 материалов для самостоятельного изучения, 1 тест
7 видео
Introduction3мин
Part 1 - Perspective11мин
Part 214мин
Part 316мин
Part 425мин
Part 526мин
Part 67мин
2 материала для самостоятельного изучения
Figures in this module10мин
Readings (to be read before lectures 4-6)10мин
1 практическое упражнение
Beadle & Tatum10мин
2
Раздел
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.
Although this work was well known, most scientists were not convinced of the general implication of this phenomenon. Furthermore, many biochemists believed that even the purified DNA was contaminated with a protein. Finally, transformation was a very inefficient process and the mechanism of transformation remained mysterious for many years.
The work of Hershey and Chase finally convinced the scientific community that genes are made of DNA.
We now realize that exchange of DNA by transformation is very common, and participates to the horizontal transfer of DNA between at least bacterial species, and was a considerable accelerator of evolution
7 видео (всего 95 мин.), 2 материалов для самостоятельного изучения, 1 тест
7 видео
Part 118мин
Part 213мин
Part 39мин
Part 413мин
Part 511мин
Part 610мин
Part 7 - Quantitative analysis of transformation19мин
2 материала для самостоятельного изучения
Figures in this module10мин
Readings (to be read before lectures 4-6)10мин
1 практическое упражнение
Avery Questions20мин
3
Раздел
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.
At that time, it was not even clear that bacteria had genes and most bacteriology work was only descriptive. The use of a quantitative approach allowed the authors to settle the question. The fluctuation test is a very powerful tool to calculate mutation rates.
Soon after, Newcombe did a simple but elegant experiment to demonstrate that the increased number of resistant bacteria that are detected upon clonal expansion reflects both the amplification of preexisting mutants and the continuous occurrence of new mutations.
4 видео (всего 77 мин.), 2 материалов для самостоятельного изучения, 1 тест
2 материала для самостоятельного изучения
Figures in this module10мин
Readings: Read the papers before watching Part 3 & Part 410мин
1 практическое упражнение
Origin of mutations14мин
4
Раздел
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.
5 видео (всего 69 мин.), 2 материалов для самостоятельного изучения, 1 тест
2 материала для самостоятельного изучения
Figures in this module10мин
Read the papers before watching parts 3 to 510мин
1 практическое упражнение
DNA structure and the fidelity of replication14мин
4.7
Лучшие рецензии
автор: BS•Mar 25th 2016
Outstanding: the classic papers are always the best primary source of information!
автор: SW•Jun 1st 2016
Very cool. Love to hear about these scientists and their lives and efforts
Преподаватель
Dominique Belin
ProfessorDepartment of Pathology and Immunology University of Geneva Medical School
О University of Geneva
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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