DOC PREVIEW
Berkeley MCELLBI 140 - “Bacterial” genetics

This preview shows page 1-2-3 out of 9 pages.

Save
View full document
View full document
Premium Document
Do you want full access? Go Premium and unlock all 9 pages.
Access to all documents
Download any document
Ad free experience
View full document
Premium Document
Do you want full access? Go Premium and unlock all 9 pages.
Access to all documents
Download any document
Ad free experience
View full document
Premium Document
Do you want full access? Go Premium and unlock all 9 pages.
Access to all documents
Download any document
Ad free experience
Premium Document
Do you want full access? Go Premium and unlock all 9 pages.
Access to all documents
Download any document
Ad free experience

Unformatted text preview:

1MCB 140 09-19-08 1“Bacterial” geneticsMCB 140 09-19-08 2“What are the genes? What is the nature of the elements of heredity that Mendel postulated as purely theoretical units? … Frankly, these are questions with which the working geneticist has not much concern himself…If the gene is a material unit, it is a piece of a chromosome; if it is a fictitious unit, it must be referred to a definite location in a chromosome. … Therefore, it makes no difference in the actual work in genetics which point of view is taken.”T.H. Morgan The Relation of Genetics to Physiology and MedicineNobel Lecture, June 4, 19343MCB 140, 2/25/05DNA Æ RNA Æ proteincentral dogma of molecular biologyMCB 140 09-19-08 47.20MCB 140 09-19-08 5Max Delbrück (1906 -1981) & Salvador Luria (1912 - 1991), Cold Spring Harbor Laboratory, Long Island NY, Summer 1941 MCB 140 09-19-08 6Today even the layman thinks of resistant bacteria as originating from mutation …but when Luria and Delbrück first got together, conventional bacteriologists were by no means clear that microorganisms could be tought about genetically… Many believed that resistance was some kind of adaptation induced, in a few of the bacteria in a culture, by the exposure to the antibacterial agent.Judson p. 552MCB 140 09-19-08 7The idea smacks of the pre-Mendelian, pre-Darwinian notion of the inheritance of acquired characteristics; Luria damned bacteriology as the “last stronghold of Lamarckism.”Judson p. 55MCB 140 09-19-08 8Let’s all do science in NevadaOne Saturday evening … Luria went to a faculty dance… There, watching the fluctuating returns obtained by colleagues gambling on a slot machine, he thought of the experiment that would distinguish between resistance induced in bacteria and resistance resulting from previous spontaneous mutation upon which selection acts. Judson p. 55MCB 140 09-19-08 9What Luria perceived was that previous spontaneous mutation would pay out jackpots of resistant bacteria that would fluctuate much more widely in size than those paid out by induction. He tried the first experiment on the following morning and wrote off to Delbrueck; Delbrueck promptly replied that Luria really ought to go to church …Judson p. 55MCB 140 09-19-08 107.4MCB 140 09-19-08 11What Luria actually didSample set A:1. Inoculate bacteria into individual cultures (1 bacterium per culture).2. Let it grow up to a large number.Sample set B:1. Take an aliquot of bacteria, and start a culture (which will therefore not be clonal).2. Let them grow up to a large numberExpose both to phage, and count, how many phage-resistant colonies per culture are found. Ask, if there is a difference between these two sample sets.MCB 140 09-19-08 12S. Luria, M. Delbrück (1943)Mutations of bacteria from virus sensitivity to virus resistance. Genetics 28: 491-511.“If the production of resistance began only at the moment of exposure to phage, then it wouldn’t matter whether the bacteria came from many individual cultures or one bulk culture. … When Luria performed the experiment, though, the twenty separate cultures showed much wider fluctuations from the average number of resistant colonies, indicating that a few of the individual tubes contained resistant bacteria from near the beginning of the overnight growth period.”Judson p. 563MCB 140 09-19-08 13Brock p. 59MCB 140 09-19-08 14MCB 140 09-19-08 15 MCB 140 09-19-08 16George Beadle (left) and Edward Tatum (right) receiving their Nobel PrizesMCB 140 09-19-08 17Nature Reviews Genetics 3, 397-403MCB 140 09-19-08 18Beadle and Tatum: the rationaleIn 1940, while teaching at Stanford, Tatum reviewed the nutritional-growth-factor requirements that distinguish related bacterial species. This raised the question of whether mutations can lead to nutritional requirements in species that do not already require a growth factor. As Beadle was already familiar with Neurospora from his contact with Dodge and Lindegren, he recognized it as an ideal organism with which to pursue this question. First, Neurospora could be grown on a simple minimal medium that contained inorganic salts, sucrose and a single vitamin. The idea of imposing further nutritional requirements by mutation was plausible. Moreover, Neurospora cultures were haploid, and therefore recognition of recessive, loss-of-function mutations should be straightforward. And most importantly, Neurospora had orthodox Mendelian genetics, an attribute that would be vital in a continuing dispute about the role of genes — the idea still persisted among embryologists that the fundamental information regarding body plan, organ systems and the 'epigenetic' features of development lay in the cytoplasm. Beadle and Tatum did their experiments in part to convince many sceptical biologists that genes control the fundamental processes of life, and not just the final touches of development, such as wing shape or eye pigment. To show this, it was important to use a eukaryote that was simpler than Drosophila and to focus on metabolic functions that could not possibly be considered as final touches.Nature Reviews Genetics 3, 397-4034MCB 140 09-19-08 19Beadle and Tatum:the beginnings"Observing him [Tatum] writing sequences of reactions on the blackboard, I suddenly realized how stupid we had been all these years. Here were all those enzymatic reactions already worked out by competent biochemists. If our gene–enzyme concepts were correct, then we ought to be able to identify the genes immediately responsible for specifically known enzyme-catalysed reactions. So why not reverse the approach? Instead of looking for reactions by enzymes controlled by known genes, why not look for genes that control already known chemical reactions? We might then expect to find mutations ... characterized by an inability to synthesize essential diffusible substances such as vitamins, amino acids and other building blocks of the cell's protoplasm."Nature Reviews Genetics 5, 949-954MCB 140 09-19-08 20Thirty points on the midterm, so wake upNature Reviews Genetics 5, 949-954MCB 140 09-19-08 21Ka-BOOOMIt took Beadle and Tatum only 5 months to find the first 3 nutritional mutants in their irradiated cultures; one required pyridoxin, another needed p-aminobenzoic acid and the third required thiamin.The first public announcement of their accomplishment was at a Caltech seminar where Beadle went to recruit people for his research group. Not


View Full Document

Berkeley MCELLBI 140 - “Bacterial” genetics

Documents in this Course
CLINE 5

CLINE 5

19 pages

Prions

Prions

7 pages

Cline 10

Cline 10

15 pages

Cancer

Cancer

18 pages

CLINE 11

CLINE 11

19 pages

Cancer

Cancer

71 pages

Notes

Notes

12 pages

Midterm

Midterm

7 pages

The Gene

The Gene

17 pages

Two loci

Two loci

77 pages

Load more
Download “Bacterial” genetics
Our administrator received your request to download this document. We will send you the file to your email shortly.
Loading Unlocking...
Login

Join to view “Bacterial” genetics and access 3M+ class-specific study document.

or
We will never post anything without your permission.
Don't have an account?
Sign Up

Join to view “Bacterial” genetics 2 2 and access 3M+ class-specific study document.

or

By creating an account you agree to our Privacy Policy and Terms Of Use

Already a member?