Parasitic organisms depend upon evasive genetic strategies towards defense, including adaptive protein diversification. Although this phenomenon has not been widely examined in subsurface ecosystems, my recent assessment of subseafloor and subterranean archaeal genomes revealed a prodigious driver of protein evolution (Paul et al. 2015). Here, I propose to expand upon this discovery, leveraging the C-DEBI collaborative network, to examine the role of targeted protein diversification in shaping host-parasite interactions in subseafloor ecosystems. Importantly, I propose to investigate this mechanism in the following three stages: 1) directly probe methane seep sediments sampled from the Santa Monica Basin, using a novel screening assay for known genetic diversifiers; 2) conduct metagenomic sequencing and bioinformatic analysis for samples prioritized in the previous step; 3) in collaboration with current C-DEBI researchers, apply newly developed bioinformatic tools to screen for latent hypervariable proteins in existing subseafloor metagenomes. This research will directly address C-DEBI phase-II research themes 2 and 3 by investigating a targeted mechanism thought to drive protein evolution in subsurface microorganisms and their viruses. The collective efforts of this proposal will lead to a broad collaboration for the identification and annotation of proteins that have evolved through adaptive diversification in subseafloor microorganisms.