Constructing the Molecular Tree of Life using Assembly Theory and Mass Spectrometry

Abstract: Here we demonstrate the first biochemistry-agnostic approach to map evolutionary relationships at the molecular scale, allowing the construction of phylogenetic models using mass spectrometry (MS) and Assembly Theory (AT) without elucidating molecular identities. AT allows us to estimate the complexity of molecules by deducing the amount of shared information stored within them when . By examining 74 samples from a diverse range of biotic and abiotic sources, we used tandem MS data to detect 24102 analytes (9262 unique) and 59518 molecular fragments (6755 unique). Using this MS dataset, together with AT, we were able to infer the joint assembly spaces (JAS) of samples from molecular analytes. We show how JAS allows agnostic annotation of samples without fingerprinting exact analyte identities, facilitating accurate determination of their biogenicity and taxonomical grouping. Furthermore, we developed an AT-based framework to construct a biochemistry-agnostic phylogenetic tree which is consistent with genome-based models and outperforms other similarity-based algorithms. Finally, we were able to use AT to track colony lineages of a single bacterial species based on phenotypic variation in their molecular composition with high accuracy, which would be challenging to track with genomic data. Our results demonstrate how AT can expand causal molecular inference to non-sequence information without requiring exact molecular identities, thereby opening the possibility to study previously inaccessible biological domains.