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Population and mutation


The complexity of a sequence of nucleotides
Manfred Eigen Scientist
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A sequence of nucleotides, if you talk about nucleic acids, has say N positions, N and a G in a thousand positions or whatever. If you write a sequence space then each position will define a dimension. In other words, if you are standing on a certain point you can migrate into N different directions, regarding... to the position which changes. Let's say you have a given sequence and now there is a change in the tenth position. Alright. You go in that dimension. Or there is a change in the 150th position. You go that way. So it's very similar as doing a mountain trip. What are you doing if you go on a mountain?

[Q] So I understand that using a landscape, a multi-dimensional landscape for what we have no real imagination is, so to speak, a analogy to explain the status of the nucleic acid. In the sense that you just say that... how big is the chance of having a mutant here and there? So it is just a transposition into another world to explain the complexity of a nucleic... is that right?

That's correct. But you have to say in addition it doesn't need to be nucleic acid, but nucleic acid is something we can quantify... a sequence. We can exactly say which base is in that position, and we can compare to the other... is it the same or is it a different one? Now, the assumption behind it is that changing any of the bases will change the property of the molecule. Or later, if it is going to be translated into a protein, will change the property of the protein. Sometimes this will not change, then we talk about neutral mutants. So wherever you have some complex - and you had this in population genetics too, these were humans or animals or so - but you couldn't quantify it. But the properties are also consisting of many, many influences and elements and so, in order to describe them quantitatively you need high dimensional spaces. For each property you need a dimension. And that's exactly what happens if we do evolution, let's say, of a sequence of nucleic acids. We are in a high dimensional landscape, we need populations, that's very important, that's filling the basin with water droplets. If you have only one water molecule, nothing would happen, you must build up a population. The same is true with nucleic acids. Evolution without populations doesn't make sense, not a single molecule or a single entity doesn't evolve, a population evolves, and that this population is extended in space here means that it consists of many different mutants. And you see, if you have a sufficiently large population and you are in this high dimensional space, it's not so difficult to reach the next optimal step.

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: nucleotide, mutant, neutral mutants, nucleic acid, fitness landscape

Duration: 3 minutes, 38 seconds

Date story recorded: July 1997

Date story went live: 24 January 2008