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In this paper we study the relationships between plants and extinct megafauna by examining the characteristics of the vegetation in the central region of Argentina (i.e. Espinal, Monte, and Chaco phytogeographic regions). First, we study the size, shape, quantity, and characteristics of fruits and seeds. We also evaluate the presence of mechanical (spinescence and wood density) and chemical (secondary metabolic compounds) defenses against high rates of herbivory. Complementarily, we assess the importance these plants had for human populations, using archeological, ethnographic, and current data. A high percentage of the analyzed plants met the criteria proposed for fruits and seeds dispersed by megafauna, together with a high frequency of spinescence, high density woods, and secondary metabolites. We propose that these traits cannot be explained by the herbivory pressure of extant fauna in the area, but rather developed in interaction with currently extinct fauna. We suggest that Pleistocene megafaunal extinction had important consequences in the region due to their role as ecosystem engineers and to vegetation's characteristics, which were probably strongly shaped by megafauna activities. Among these consequences, we discuss the loss of certain interactions between these animals and vegetation, such as loss of seed dispersal mechanisms, shrub invasion, and increased susceptibility of vegetation to fire. Other effects for hunter-gatherer groups were the generation of highly regulated mobility patterns and the formation of barriers for the dispersal of prey. Finally, we also discuss the importance of these plants for human populations as food, construction material, medicines and firewood. Likewise, the role of humans as "heirs" of the megafauna in the propagation of tree and shrub species is highlighted. [ABSTRACT FROM AUTHOR]