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Background: Deserts are biologically rich habitats with a vast array of animals and plants adapted to xeric conditions, and most deserts are among the planet's last remaining areas of total wilderness. Among North American deserts, the Chihuahuan Desert has the highest levels of diversity and endemism. To understand the effect of future climate change on plants distributed in this arid land and propose effective conservation planning, we focused on five endemic shrubby species that characterize the Chihuahuan Desert and used an integrative approach. Methods: Ecological niche-based modeling, spatial genetics and ecological resistance analyses were carried out to identify the effect of global warming on the studied five shrubby species. Key areas that need to be preserved were identified taking into account the existing protected areas within the Chihuahuan Desert. Results: The extent of future distribution will vary among these species, and on average expansion will occur in the western part of the Chihuahuan Desert. For most species low environmental resistance to gene flow was predicted, while higher future resistance was predicted for one species that would lead to increased population isolation. The highest haplotype diversity was identified in three hotspots. Based on future suitability of habitat and in the haplotype diversity we suggest preserving two hotspots of genetic diversity in the Sierra Madre Oriental, located in areas without protection. The third hotspot was detected in the well preserved Tehuacán-Cuicatlán Man and Biosphere Reserve. Conclusion: Global climate change will have an effect in arid adapted plants, favoring expansion in the western of the Chihuahuan Desert however negatively affecting others with high ecological resistance disrupting gene flow. Two hotspots of genetic diversity in the Sierra Madre Oriental should be protected. [ABSTRACT FROM AUTHOR]