Sydney Brenner on mice and men

On 27th September 2007 I had the privilege of hearing a talk by Sydney Brenner in Berlin. Brenner is a Nobel prize winner (2002) and known for his role in deciphering the genetic code, discovering messenger RNA and launching the humble worm Caenorhabditis elegans on its brilliant career as a model organism. I find that Brenner is an inspiring speaker and I had the impression of experiencing a very special source of knowledge and an exceptional individual. The talk was seasoned with critical comments on various aspects of modern molecular biology including a tough one-liner directed at systems biology. He also had something more general to say about the applications of mathematics to biology – unfortunately I do not remember the details. In any case, his variety of scientific argumentation reminded me of some of the best things about the way mathematics works.

Yesterday I discovered online videos of two talks of Brenner. I watched them and was glad I did. The first begins by talking about the redshift as a tool which can be used to obtain information about the distant past of our universe and asking if there exists something similar which could be used to explore the distant evolutionary past of life. Brenner points out that the genomes of many organisms have now been deciphered and asks what kind of information can be obtained from them. He mentions the following ‘inverse problem’. Suppose we were given just the genome of an organism without knowing the organism itself. Could we then reconstruct that organism? It seems that this is far beyond what can be done at the present time. He then goes on to discuss the question of comparing the genome of different organisms and trying to define a kind of evolutionary distance between them. As a concrete example he takes the case of mice and men.

One of the main themes of the lectures is finding ways of determining the speed at which the genome is evolving in different species. He points out that the genetic data contain no arrow of time. Thus they are equally consistent with fish evolving into human beings or fish having been formed by degeneration of previously existing human beings. The external facts that allow us to decide in which direction evolution goes come from the fossil record. The data show that the mouse genome is evolving much faster than the human genome. Getting this kind of information requires comparing the genomes of more than two species.

In what way is it possible to obtain information about the evolution of the genome? Certain types of statistical analysis of the occurrence of different bases in the genomes of different species can do this. Brenner emphasizes the important of silent mutations, those where a change in one base replaces a codon by another one corresponding to the same amino acid. An advantage of studying these mutations is the absence of selective pressure on them. What this statistics involves is anything but applying standard (perhaps powerful) methods of analysis. It rather has to do with having good ideas about what patterns to look for in the data. Brenner points out that since the genome data are freely available on the internet and the computing power required is modest it would be possible to develop home genomics. That is to say: someone could develop important new ideas for the analysis of the dynamics of the genome by playing about on their home computer.


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