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.

Protein folds as synapomorphies of the tree of life.

Several studies showed that folds (topology of protein secondary structures) distribution in proteomes may be a global proxy to build phylogeny. Then, some folds should be synapomorphies (derived characters exclusively shared among taxa). However, previous studies used methods that did not allow synapomorphy identification, which requires congruence analysis of folds as individual characters. Here, we map SCOP folds onto a sample of 210 species across the tree of life (TOL). Congruence is assessed using retention index of each fold for the TOL, and principal component analysis for deeper branches. Using a bicluster mapping approach, we define synapomorphic blocks of folds (SBF) sharing similar presence/absence patterns. Among the 1232 folds, 20% are universally present in our TOL, whereas 54% are reliable synapomorphies. These results are similar with CATH and ECOD databases. Eukaryotes are characterized by a large number of them, and several SBFs clearly support nested eukaryotic clades (divergence times from 1100 to 380 mya). Although clearly separated, the three superkingdoms reveal a strong mosaic pattern. This pattern is consistent with the dual origin of eukaryotes and witness secondary endosymbiosis in their phothosynthetic clades. Our study unveils direct analysis of folds synapomorphies as key characters to unravel evolutionary history of species.