Karolinska Research Lectures – Michael Lynch

//Karolinska Research Lectures – Michael Lynch

Karolinska Research Lectures at NOBEL FORUM
April 16, 16.30

Michael Lynch
Department of Biology, Indiana University, Bloomington, USA

Title: Mutation, Drift, and the origin or subcellular features

Although natural selection may be the most powerful force in the biological world, it is not all powerful. As a consequence, many aspects of evolution of the molecular level can only be explained by the inability of natural selection to operate. This general principle explains a lot about the evolution of genome architecture, and also appears to extend to multiple higher-level features of cells, as most clearly demonstrated with observations on replication fidelity.
Understanding the mechanisms of evolution and the degree to which phylogenetic generalities exist requires information on the rate at which mutations arise and their effects at the molecular and phenotypic levels. Although procuring such data has been technically challenging, high-throughput genomic sequencing is rapidly expanding our knowledge in this area. Most notably, information on spontaneous mutations, now available in a wide variety of organisms, implies an inverse scaling of the mutation rate (per nucleotide site) with the effective population size of a lineage. The argument will be made that this pattern naturally arises as natural selection pushes the mutation rate down to a lower limit set by the power of random genetic drift rather than by intrinsic molecular limitations on repair mechanisms or by selection for an optimum mutation rate.

This drift-barrier hypothesis has general implications for all aspects of evolution, including the performance of enzymes, the stability of proteins, and the refinement of transcription-factor binding sites. The fundamental idea here is that as molecular adaptations become more and more refined, the room for subsequent improvement becomes diminishingly small. If this hypothesis is correct, the population-genetic environment imposes a fundamental constraint on the level of perfection that can be achieved by any molecular adaptation, and indeed all adaptations. Additional examples consistent with this hypothesis will be drawn from recent observations on the transcription-error rate and on the evolution of the oligomeric states of proteins.

Host: Jussi Taipale, Karolinska Institutet, email:

Contact: Tatiana Goriatcheva, Nobel Office, Nobel Forum,
tel. 524 87805,