Challenges posed by chaotropic environments are difficult for life as they decrease water activity and disrupt fundamental cellular functions. Chaotropes, like magnesium chloride, disrupt hydrogen bonding between water molecules deteriorating the hydrophobic properties of membranes, nucleic acids, and proteins; leading to cell death. Extremely chaotropic environments on Earth, such as MgCl2 saturated deep-sea hypersaline anoxic basins (DHABs) also provide windows to interplanetary bodies such as Martian brines, and the deep subsurface oceans on the frozen moons of Enceladus, Titan, and Europa. Therefore, studying the microbiome of DHABs and other chaotropic environments are essential in the field of astrobiology. However, research of microbial adaptations in these harsh conditions is lacking. The purpose of this study is to identify genes associated with adaptation in chaotropic and low water activity environments. Published genomes of chao-tolerant microbes on the Integrated Microbial Genomes (IMG) web-based platform will be analyzed using comparative genomics approaches to differentiate between essential and inconsequential genes to distinguish chaophilic and xerophilic adaptations. In particular, the genomes of Halobacterium salinarum NRC-1 and Haloquadratum walsbyi C23, globally distributed halophiles found in brines and salterns that have vastly different chao-tolerances, will be compared and analyzed using PATRIC, an integrated genomic analysis tool. The goal of this study is to identify genes and cellular mechanisms that could confer adaptation to chaotropic conditions. Further study of life in chaotropic and low water activity brines such as DHABs has the potential to broaden the limits of life on Earth, and elsewhere.