Life on Mars, if it exists, may be related to life on Earth. This common ancestry hypothesis is supported by theoretical and experimental studies of meteoritic exchange between Earth and Mars, exchange that could have spread life between those planets. If so, we can target the basic building blocks of life, DNA or RNA, in our search. We are developing the Search for Extra-Terrestrial Genomes (SETG) instrument with the goal of isolating, extracting, and sequencing nucleic acids in-situ on Mars. Here we outline the major challenges and approaches to achieve this goal, with an emphasis on the sample preparation required to isolate nucleic acids from Mars-like samples. Looking for nucleic acids is not the most general approach to search for life on Mars. However, given the possibility of common ancestry, it is a critical part of any comprehensive life detection strategy, arguably unmatched in its ability to provide a highly sensitive and specific detection and characterization of any life on Mars related to life on Earth.
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