Origins and Functional Significance of Eukaryotic Protein Folds.

Folds are the architecture and topology of a protein domain. Categories of folds are very few compared to the astronomical number of sequences. Eukaryotes have more protein folds than Archaea and Bacteria. These folds are of two types: shared with Archaea and/or Bacteria on one hand and specific to eukaryotic clades on the other hand. The first kind of folds is inherited from the first endosymbiosis and confirms the mixed origin of eukaryotes. In a dataset of 1073 folds whose presence or absence has been evidenced among 210 species equally distributed in the three super-kingdoms, we have identified 28 eukaryotic folds unambiguously inherited from Bacteria and 40 eukaryotic folds unambiguously inherited from Archaea. Compared to previous studies, the repartition of informational function is higher than expected for folds originated from Bacteria and as high as expected for folds inherited from Archaea. The second type of folds is specifically eukaryotic and associated with an increase of new folds within eukaryotes distributed in particular clades. Reconstructed ancestral states coupled with dating of each node on the tree of life provided fold appearance rates. The rate is on average twice higher within Eukaryota than within Bacteria or Archaea. The highest rates are found in the origins of eukaryotes, holozoans, metazoans, metazoans stricto sensu, and vertebrates: the roots of these clades correspond to bursts of fold evolution. We could correlate the functions of some of the fold synapomorphies within eukaryotes with significant evolutionary events. Among them, we find evidence for the rise of multicellularity, adaptive immune system, or virus folds which could be linked to an ecological shift made by tetrapods.