In a review by Bohl and colleagues, which appeared in the August issue of Molecular Biosystems, the principles of game theory are applied to subcellular macromolecules such as RNA, DNA and proteins. The authors recast molecules as “players” who use various strategies to achieve the goals of their host cell/organism, or selfishly, their own goals. We can “consider the result of some mutations or epigenetic modifications as changes in strategy”.
From an evolutionary standpoint the overall goal of an organism is to reproduce. Therefore, any macromolecules that affect reproduction can be considered players. This is especially true of DNA, which can be considered successful if it is able to replicate. Typically we think of genes which persist in a population as beneficial to the host organism, i.e. if a gene were detrimental, that organism would be less likely to reproduce and the gene would disappear from the population. These genes would be said to cooperate in order to promote the success of the carrier organism. However, genes can also act in their own self interest, and be detrimental to the host.
The authors describe three ways for genes to be “selfish”, interference, overreplication and gonotaxis. Interference is the gene preventing the transmission of other genes to the daughter cells, thus increasing its own chances of transmission. The gene can also replicate more than once in a cycle, using overreplication to achieve the same goal. Gonotaxis is more complicated, in that the genes have to avoid being sequestered into non-functional polar bodies during meiosis (see Figs. 1-3 below for diagrams).
Interestingly, genes that are typically selfish can actually be beneficial in some circumstances. Some bacteria have toxin genes that may have been useful to avoid predators in some circumstances. In the absence of a need for toxin, the cells express “anti-toxin” as a control. Also, jumping genes are sometimes viewed as parasitic because they are usually not crucial to the survival of an organism. However, in the case of arabidopsis, a lack of the “DAYSLEEPER” jumping gene causes growth defects.
Some of the same reason that DNA can be considered players also apply to proteins. For protein complexes in particular the authors consider a game with two players, where the goal is to form a bond. Each protein can be either flexible or rigid. If both are rigid, binding is difficult, and depends on an exact matching of shapes. If both are flexible then binding is easy, but the resulting complex will lack a defined shape. Therefore, the best outcome requires one protein to be rigid, and one to be flexible. This model fits well with recent findings (cited in this paper) of unstructured/disordered regions of proteins which form secondary structure when binding to another protein (induced fit model, see Fig. 4 below).
The ideas of game theory as presented by Bohl et al. are best applied to information encoding macromolecules, such as RNA, DNA and proteins. These principles can be applied to common genetics questions such as “jumping genes”, as well as understanding the activity of disordered proteins.
Evolutionary game theory: molecules as players
Katrin Bohl, Sabine Hummert, Sarah Werner, David Basanta, Andreas Deutsch, Stefan Schuster, Gunter Theißen and Anja Schroeter
Anja Schroeter webpage at Friedrich-Schiller-University Jena (page not in English!)