Theoretical Evolutionary Genetics, CMAF, Lisbon University, Portugal

Genetic linkage and mutation rate instability

We propose a new hypothesis that clonal evolution is fundamentally flawed due to mutation rate instability: under strong genetic linkage, adaptation by natural selection makes this instability strongly asymmetric, thereby driving mutation rates to intolerable levels and causing the population to abruptly go extinct Ð a process that has been dubbed the "mutation-rate catastrophe".

I will describe the population-biological process, briefly outline the theory, present preliminary experimental data, and discuss potential applications, including possible implications for a new mode of action of the immune system.

Microsoft Research, Trento, IT

Dynamic spatial games to understand cooperation in tumor formation

Authors: Matteo Cavaliere, Tarcisio Fedrizzi, Ferenc Jordán, Sean Sedwards & Attila Csikász-Nagy

Abstract: We propose a generative model, named "dynamic spatial game" (DSG) as an extension of "spatial game" proposed by Nowak and May [1]. DSG combines graph transformations and game theory to describe the role of cell-to-cell interactions during tissue formation and cancer development. The nodes of the graph represent cells and spatial interactions in the tissue are represented by the edges. Each cell acts as a player of a "game" where it interacts with its neighbors by sharing growth factors, apoptotic or anti-apoptotic signals etc., which determine the fitness of the cell. Depending on the gained fitness the cell divides, rests in G0 or dies. In the next step the graph is updated dynamically by adding or removing nodes, simulating a 2D tissue [2]. We test the role of cooperation in tissue formation and tumor development by simulating the dynamic spatial games of normal, mutated and multi-mutated (tumor) cells, where partially transformed mutated cells cooperate by sharing resources [3]. We investigate how the mutation rate and cooperation strength influences the timing of cancer development and discuss possible further extensions of the model to understand how cell-to-cell interactions influence cancer development.

[1] M. Nowak, R.M. May, (1992) Evolutionary games and spatial chaos, Nature, 359, 826 - 829.

[2] S. Bar-Duvdevani, L. Segel, (1994) On topological simulations in developmental biology, J Theor Biol, 166, 33-50.

[3] R. Axelrod, D.E. Axelrod, K.J. Pienta, (2006) Evolution of cooperation among tumor cells, PNAS, 103, 13474-9.