Natural selection occurs at all levels of biological organization. At higher levels it favors cooperation between lower-level units and at lower levels it favors cheaters that exploit the common good for their own interests. The corresponding molecular mechanisms are best characterized for the replication control genes of plasmids in Escherichia coli that face selection at two distinct levels: plasmid copies that systematically over-replicate relative to their cellmates have a higher chance of fixing in descendent cells, but these cells typically have a lower chance of fixing in the population. To analyze the conflict, the mathematical frameworks for multi-scale selection and drift in cells will be extended, focusing on conflict suppression mechanisms, meta-control of selfishness, and how cooperation is prevented by clonal interference. In addition, an experimental platform will be developed to test how different conditions select for altruism or selfishness, and monitor the dynamics of the conflict by mapping arising mutations to the known control systems.
All social elements--from microorganisms to humans--can benefit from both cooperation and selfishness, and the most successful behavior depends on the parameters of the social scene. The investigators have identified a clean-cut conflict between selfish and altruistic elements in one of the simplest and best studied processes in bacterial cells: Self-replicating pieces of DNA get an immediate advantage by selfishly over-reproducing, but then instead indirectly suffer because they impose a larger burden on the cells upon which they rely. Because other aspects of this system are so well-studied, this provides a unique opportunity to rigorously analyze a complex phenomenon like cooperation in terms of molecular mechanisms and physical chemistry. General rules for such conflicts will be mathematically derived and experimentally tested, determining conditions for altruistic behavior and identifying mechanisms that enhance or suppress selfishness. By focusing on testable theorems and broad intuitive principles, the results are equally important for education and research.
Organisms in nature compete for resources and evolution favors those that reproduce the most. This generally prevents altruistic behavior. For example, predators who spare pray at their own expense will on average produce fewer off-spring, making the behavior less prevalent in the next generation. However, for social organisms there are many mechanisms by which forms of altruism can be promoted by evolution, for example when groups of individuals partially share the same fate. Competition within groups then favors selfishness while competition between groups favors altruism, just like cancer cells temporarily benefit from failing to recognize growth inhibition signals, but out-reproduce their fellow cells to the ultimate demise of the organism. Similar conflicts arise even within single cells. For example, bacterial plasmids – one of the most common types of self-replicating molecules in the biosphere – exist in multiple copies per cell. If a mutant plasmid copy self-replicates more than the others – consuming a disproportionate fraction of the resources – it can outcompete its cell mates. However, once the cells contain only selfish mutants, those cells will be outcompeted by cells with more altruistic copies. Thus from one perspective it seems that selfish copies always win and from the other perspective it seems that altruists always win. We took a jointly mathematical and experimental approach to this problem. We used mathematical methods from random processes to analyze the principles of cooperation and defection for plasmids. Specifically, the approach recognized that the advantage selfish plasmids have inside the cell, or the disadvantage they have once they are in their own cells, is not absolute but only results in different probabilities of taking over. The probabilities depend the parameters of the system, allowing us to compare the relative strengths of the selective pressures and predict under what conditions selfishness or altruism should evolve. We then built specialized growth chambers to observe the long-term evolution of plasmids, allowing us to take samples and sequence mutations as they arise. Previously, such experiments suffered from several technical challenges, for example that cells grew on the walls of the growth chambers preventing long-term competition experiments. We built a series of machines to get around this challenge. We believe our final device will allow us to cover tens or even hundreds of thousands of generations – almost as many generations as are thought to separate humans and chimpanzees. We also had many other significant successes along the way, developing methods to more accurately measure many aspects of plasmid biology. However, our final question remains largely unresolved and we have much more work to do before we truly understand the mechanisms of selfishness and altruism in these systems.
