%0 Journal Article %A Betul Kacar %A Lionel Guy %A Eric Smith %A John Baross %T Paleophenotype reconstruction as a window into historic biological states %D 2017 %R 10.1101/164038 %J bioRxiv %P 164038 %X The conditions for life in the deep past were different in many important ways from conditions of life on Earth today. Simple sequence-based comparative methods of evolutionary reconstruction, applied to single genes or proteins, can therefore give an incomplete or misleading picture of ancestral life forms. One way to augment sequence-based, single-gene methods to obtain a richer and more reliable picture of the deep past, is to resurrect inferred ancestral protein sequences in living organisms, where their phenotypes can be exposed in a complex molecular-systems context, and to then link consequences of those phenotypes to biosignatures that were preserved in the independent historical repository of the geological record. Good candidates for such ‘revenant gene’ studies are the genes for enzymes involved in carbon-fixation or other core metabolic pathways. Resurrecting ancestral DNA using synthetic-biology methods to engineer modern host bacteria is just at the beginning of its use as a systematic method in evolutionary biology. It has great potential to refine our understanding of the historical era already probed by phylogenetic methods, and even to suggest the forces governing the assembly of living systems reaching back into the “pre-historic” past, before those sequence divergences that have left descendants into the modern era. However, good design of revenant gene studies introduces new and interesting problems in the selection of genes, biosignatures, and modern host organisms, which should be understood as part of the next step in advancement of evolutionary methods. %U https://www.biorxiv.org/content/biorxiv/early/2017/07/15/164038.full.pdf