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Unicellular organisms are popular models for long-term laboratory evolution, but commonly used bacteria and yeasts have limited amount of morphological features suitable as visible markers of population changes. Filamentous fungus Podospora anserina is easy growing true multicellular eukaryotic organism that has well developed vegetative mycelium and generative structures. Using of P. anserina as a model object allows observe changes at three levels of biological organization: genomic, physiological and morphological. Present permanent evolution experiment has been started in 2012. Eight independent P. anserina cultures are growing by serial passages into liquid medium. Experimental conditions of growth provoked many irreversible changes in fungal mycelia including intensification of biomass accumulation, loosing of possibility to realize sexual process, loosing of melanin pigmentation and others. Being removed from liquid to agar medium (initial control conditions) P. anserina isolates never give back the wild type again. Genomic changes in three available experimental P. anserina lines have been analyzed and compared with initial strain of wild type. The more passages in liquid the fungus underwent the more mutations could be revealed in its genome. It is interesting to notice that frequency of mutations detected in coding regions is noticeably higher than it could be expected in the case of random accumulation of mutations. So accumulation of specific genomic changes may be the way for the fungus to adapt to unusual conditions. Cells of modified mycelia have been characterized by very thin cell walls with no additional protective layers or covers and numerous nuclei having big nucleolus. Special characteristic of adapted P. anserina isolates was absorption of huge parts of cytoplasm by intracellular vacuoles. Analysis of ultrastructural data confirms that main direction of all changes come to adapt for living at conditions of easy accessible food and stability. The reported study was partially supported by RFBR, research project No. 16-04-01845 a.