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Continued experiments in molecular genetics (Part 1)

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Discovering other mutants
Sydney Brenner Scientist
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In the meantime, we had discovered that there was another nonsense mutant, and because the amber had been called amber, I called them ochre mutants: O-C-H-R-E. So ambers and ochres was the thing, and we then discovered that there were a whole different set of suppressors for this. And there was a third kind of nonsense we suspected, and which took us quite a long time to find. And eventually we did find it, but by that time we'd got tired of these colours, although they had been called opal by someone and they did remain. I did… I thought for a moment I would call them umber mutants, but then I realised this wouldn't go down in England, you see, because there are parts of England where amber is umber and umber is oombah, you see, so there'd be a lot of confusion. So we left it at that. Now, what was very interesting was could we find the triplets for these nonsense mutants. And there is an experiment that I did, which was published together with some colleagues, which involved the protein synthesis, but the genetic experiment is the one I'm extremely proud of. It's still used in teaching in America to students as a classic. I... you... I could by making certain assumptions about mutagenesis, decide whether I was having, going from C to U, or what's equivalent, G to A, but I'd have to, to decode the triplet, know which chain I was working on because the DNA is double-stranded. So we know the message strand is only one of these. The other is complementary. So experiment involved the following. It asked this: it says, 'How many mutants can you record after chemical mutagenesis immediately?' That is, on the restrictive strain. And how many more do you get when you go through an unrestricted strain first? Because the mutants that are missing in the first must be those that affected the sense strand. And that was a lot of work, but it was quite easy, so you had to conduct… you had to make two mutant spectra. So it involved making lots of mutants and mapping them, and then finding out if there was one set missing. And by knowing which set was missing, you could say whether you had a C or a G in the coding strand. And in that way I was able to prove – knowing that ambers and ochres and UGAs were connected – I was able to say that the nonsense mutants had a U, that one of them had a U and two As, one of them had a U and an A and a G, and the other one also had a U and an A and a G, but it was the other way around. And that the most likely sequence in that case was UAG, UAA, and UGA, because of their connections to amino acids. So only by that experiment, hydroxylamine mutation, and a lot of knowledge about what amino acids these were, did we fulfil just even the last bit of the original program of sequencing DNA. So I like to say I did do it, I did sequence three bases in DNA by genetics in this case. But that was the last sort of thing, and then from then on it was just… it had all become biochemistry.

South African Sydney Brenner was awarded the Nobel Prize in Physiology or Medicine in 2002. His joint discovery of messenger RNA, and, in more recent years, his development of gene cloning, sequencing and manipulation techniques along with his work for the Human Genome Project have led to his standing as a pioneer in the field of genetics and molecular biology.

Listeners: Lewis Wolpert

Lewis Wolpert is Professor of Biology as Applied to Medicine in the Department of Anatomy and Developmental Biology of University College, London. His research interests are in the mechanisms involved in the development of the embryo. He was originally trained as a civil engineer in South Africa but changed to research in cell biology at King's College, London in 1955. He was made a Fellow of the Royal Society in 1980 and awarded the CBE in 1990. He was made a Fellow of the Royal Society of Literature in 1999. He has presented science on both radio and TV and for five years was Chairman of the Committee for the Public Understanding of Science.

 

 


Listen to Lewis Wolpert at Web of Stories

 

 

Tags: USA, UK

Duration: 4 minutes, 13 seconds

Date story recorded: April-May 1994

Date story went live: 24 January 2008