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Finding a ridge in sequence space


The progress of evolution
Manfred Eigen Scientist
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The advantages... the progress of evolution if you adapt to new environmental conditions means that you have to look for new things, because within the quasispecies you have rated everything... evaluated everything. So if you look for new mutants, they will appear at the periphery of the quasispecies. Now what is the chance that you'd find a fit mutant? People always say, 'Well, the chance to have an advantage as a mutant is very, very low, almost all mutants are disadvantages'. That's true. But the disadvantageous mutants don't appear. Why not? Because you have this very far distributed population of mutants, so the distance from the centre of gravity of the distribution is many mutations... several mutations. So at the periphery any mutant does not appear by 'mis-copying' the wild type, that means the centre of gravity. It will appear by 'mis-copying' one of the mutants at the periphery. And those mutants which are almost as good as the wild type... as the average of it, as the... which are neutral, they are populated, like the... So in other words there is a rating within the quasispecies that the good mutants are populated... the neutral mutants are populated almost like the wild type, whereas the deleterious ones only are just formed and then disappear so they are present in very low population. So what you produce at the periphery are mutants of the good ones. And by similarity methods the probability that you get a better mutant from a good one is much larger than to get a better one from a bad one. So in other words, there is a very efficient way of testing for mutants, and we have studied this. In the experiment I have mentioned, within seventy minutes you got this completely different molecule which was able to resist to the degrading enzyme, and so how could you do that other in another way? The number of possible mutants there is astronomically high, but the system finds the right ones.  That's one of the important points.

Nobel Prize winning German biophysical chemist, Manfred Eigen (1927-2019), was best known for his work on fast chemical reactions and his development of ways to accurately measure these reactions down to the nearest billionth of a second. He published over 100 papers with topics ranging from hydrogen bridges of nucleic acids to the storage of information in the central nervous system.

Listeners: Ruthild Winkler-Oswatitch

Ruthild Winkler-Oswatitsch is the eldest daughter of the Austrian physicist Klaus Osatitsch, an internationally renowned expert in gas dynamics, and his wife Hedwig Oswatitsch-Klabinus. She was born in the German university town of Göttingen where her father worked at the Kaiser Wilhelm Institute of Aerodynamics under Ludwig Prandtl. After World War II she was educated in Stockholm, Sweden, where her father was then a research scientist and lecturer at the Royal Institute of Technology.

In 1961 Ruthild Winkler-Oswatitsch enrolled in Chemistry at the Technical University of Vienna where she received her PhD in 1969 with a dissertation on "Fast complex reactions of alkali ions with biological membrane carriers". The experimental work for her thesis was carried out at the Max Planck Institute for Physical Chemistry in Göttingen under Manfred Eigen.

From 1971 to the present Ruthild Winkler-Oswatitsch has been working as a research scientist at the Max Planck Institute in Göttingen in the Department of Chemical Kinetics which is headed by Manfred Eigen. Her interest was first focused on an application of relaxation techniques to the study of fast biological reactions. Thereafter, she engaged in theoretical studies on molecular evolution and developed game models for representing the underlying chemical proceses. Together with Manfred Eigen she wrote the widely noted book, "Laws of the Game" (Alfred A. Knopf Inc. 1981 and Princeton University Press, 1993). Her more recent studies were concerned with comparative sequence analysis of nucleic acids in order to find out the age of the genetic code and the time course of the early evolution of life. For the last decade she has been successfully establishing industrial applications in the field of evolutionary biotechnology.

Tags: quasispecies, mutants, neutral mutants, degrading enzyme, wild type

Duration: 2 minutes, 48 seconds

Date story recorded: July 1997

Date story went live: 24 January 2008