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Benefitting from less junk in Fugu DNA


Fugu: the puffer fish genome
Sydney Brenner Scientist
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Now, I tried to get these fish for quite some time. They are puffer fish. And I then decided that such is the… such is the unreliability of natural sources that we could start to work on this and find that some pollution or some fire or… or something has… has got rid of them in the world, they've become extinct. Actually today we now say that we don't care if they become extinct as long as we've got enough DNA to keep us going, or we've cloned it all. So, I then decided that I would go and get the one specimen of this fish which is actually fished and cultivated for food, in Japan. And it is the fugu – the Japanese puffer fish. Now, when I went to Japan and – to try to organise this – and I managed to organise this and people said, why are you interested in this? I said, I'll give you a little talk on junk. Nobody believed this, they said it's… the measurements must be wrong. It can't be that you have something with so little DNA, the measurements must be wrong. Well, to cut the long story short, we got this, I managed to find a group of young people to work with me, and we were able to devise a fairly reasonable way, because of course what you want to try and prove is that this fish has the same number of genes as we do, because if it only has 1/8 the number of genes it isn't interesting. And that we were able to do by what I think's a very pretty experiment. What we did is we just did – it's a new technique called statistical genomics –we just took 600 pieces of DNA randomly and sequenced them, and asked, how many genes can we find? That is genes that have already been found in other vertebrates and in particular in the mammals, that occupy most of this. And having found the probability of finding these genes we could then go and ask – because we didn't have to do the experiment – because we could then calculate what is the abundance of these genes in the genome. And what we found is it was eight times more enriched in the fugu, therefore, what we could prove is that we had the same number of genes, more or less, and everything we've done has borne that out. So I think I like to call the fugu the discount genome, because you get 90% discount on sequencing. And since I think I've enhanced the job tenfold, then I've fulfilled the great technical requirement which everybody said we should have, a tenfold step in technology every five years, and so I've done that in a few months just by choosing the right organism. Now, I think that this will now become a world-wide use. We have now a lot of people coming to our lab to… to find pieces of DNA that correspond to this, and I'm encouraging as many people to work on this, because…

[Q] It would just be helpful to explain why it's so helpful.

Well, if you… to explain why it's so helpful is the following. Let us just assume that certain groups of genes have stayed together throughout this whole period of about a half a billion years of evolution. Now, many people can map a human gene, let's say a gene for breast cancer, but they can only find it into a piece of DNA, somewhere in a piece of DNA that's a million base pairs. Right. Now, to sequence through the million base pairs and find the gene is enormously tedious and time consuming. Right? And what we are saying is, well, you'll only have to do a 100,000, a 125,000, because what you do is you start with something on this, go and get the piece of the fugu genome and then move along. And let me just say that whereas on the average a gene in man is 50,000 bases, the gene in fugu is 6,000 bases, and in fact we have now got pieces of DNA which is 40,000 base – it's called a cosmid – and on this we have as many as eight genes. Seven to eight genes is the popular thing. Therefore, what we find is that all the intervening sequences are there, they're in the same place so these are the same genes, but they are small, very tiny, and also the genes are close together. They're not separated by large amounts of junk DNA.

South African Sydney Brenner (1927-2019) 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



Duration: 5 minutes, 55 seconds

Date story recorded: April-May 1994

Date story went live: 29 September 2010