Final Report Summary - FAGM (The evolution and implications of fitness-associated genetic mixing - a theoretical study) • A description of the work performed since the beginning of the project, and the main results achieved so farWe extended our previous work (Hadany and Otto, 2009) on condition dependent sexual reproduction to cases of adaptation, and studied its effects on adaptation in two specific case of significant implications: (i) the role of stress induced HGT in the evolution of antibiotic resistance, and how it should change the use of antibiotics in hospitals (Obolski, U. and Hadany, L. Stress-induced genetic variation and its implications for choosing antibiotic treatment strategies. BMC Medicine, 10:89, 2012.)(ii) The potential role of stress on the parasexual cycle in C. albicans, the most common fungal pathogen in humans. Berman, J. and Hadany, L. Does stress drive (para)sex? Implications for C. albicans evolution.Trends in Genetics, 28, 197-203, 2012.Next, we developed mathematical models of fitness-associated outcrossing, and showed that fitness-associated outcrossing can evolve under an extremely wide parameter range, and can lead to various implications for the population as a whole (Gueijman and Hadany, submitted). We extended the theory to study the evolution of Fitness Associated Dispersal (FAD), using agent based simulations with spatial structure, and showed that fitness associated dispersal is expected to evolve under a very wide parameter range, even when the population is homogeneous and dispersal carries high costs (Gueijman et al, BMC Evol. Biol. 2013). We further showed that it has long term implications for the well being of the population as a whole.Finally, we extended our research to study the evolution of stress induced mutagenesis in asexual populations (Ram and Hadany, 2012). We have shown that stress induced mutagenesis evolves in constant environments and in changing ones. Our results suggest that if beneficial mutations occur, even rarely, then stress-induced hypermutation is advantageous for bacteria at both the individual and the population levels and that it is likely to evolve in bacterial populations. • The expected final results and their potential impact and use (including the socio-economic impact and the wider societal implications of the project so far). Genetic mixing plays a major role in the generation of variation, which is a necessary component of the evolutionary process. Despite the ubiquity and importance of genetic mixing, the rules that govern its evolutionary dynamics and regulation are still poorly understood. In particular, most models make the simplifying assumption that mixing has a uniform rate at all times. In this project we explored an alternative assumption, both harder and more realistic: that genetic mixing might in fact be plastic, its rate depending on the state of the organism. Our results imply that genetic variation - including sex, outcrossing, dispersal, and mutation - is not, as the current view holds, uniformly distributed in populations. We have shown that fitness-associated variation can evolve, and have testable predictions for the distribution of mixing events in various systems. These results would allow more realistic modeling of genetic variation, of relevance to most models of evolution and ecology. In addition to its direct theoretical significance, this research has many significant practical implications: for the evolution of drug resistance under various regimes of drug use in pathogens, and for the vulnerability of plant and animal populations undergoing extreme environmental changes, such as global warming or increased human interference.