Evolutionary history of phosphatidylinositol- 3-kinases: ancestral origin in eukaryotes and complex duplication patterns

BACKGROUND: Phosphatidylinositol-3-kinases (PI3Ks) are a family of eukaryotic enzymes modifying phosphoinositides in phosphatidylinositols-3-phosphate. Located upstream of the AKT/mTOR signalling pathway, PI3Ks activate secondary messengers of extracellular signals. They are involved in many critical cellular processes such as cell survival, angiogenesis and autophagy. PI3K family is divided into three classes, including 14 human homologs. While class II enzymes are composed of a single catalytic subunit, class I and III also contain regulatory subunits. Here we present an in-depth phylogenetic analysis of all PI3K proteins. RESULTS: We confirmed that PI3K catalytic subunits form a monophyletic group, whereas regulatory subunits form three distinct groups. The phylogeny of the catalytic subunits indicates that they underwent two major duplications during their evolutionary history: the most ancient arose in the Last Eukaryotic Common Ancestor (LECA) and led to the emergence of class III and class I/II, while the second – that led to the separation between class I and II – occurred later, in the ancestor of Unikonta (i.e., the clade grouping Amoebozoa, Fungi, and Metazoa). These two major events were followed by many lineage specific duplications in particular in vertebrates, but also in various protist lineages. Major loss events were also detected in Vidiriplantae and Fungi. For the regulatory subunits, we identified homologs of class III in all eukaryotic groups indicating that, for this class, both the catalytic and the regulatory subunits were presents in LECA. In contrast, homologs of the regulatory class I have a more recent origin. CONCLUSIONS: The phylogenetic analysis of the PI3K shed a new light on the evolutionary history of these enzymes. We found that LECA already contained a PI3K class III composed of a catalytic and a regulatory subunit. Absence of class II regulatory subunits and the recent origin of class I regulatory subunits is puzzling given that the class I/II catalytic subunit was present in LECA and has been conserved in most present-day eukaryotic lineages. We also found surprising major loss and duplication events in various eukaryotic lineages. Given the functional specificity of PI3K proteins, this suggests dynamic adaptation during the diversification of eukaryotes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12862-015-0498-7) contains supplementary material, which is available to authorized users

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Additional file 11 of Evolutionary history of phosphatidylinositol- 3-kinases: ancestral origin in eukaryotes and complex duplication patterns

Phylogenetic tree of Metazoa, Ichthyosporea and Choanoflagellida homologs of class II catalytic proteins. The tree was inferred with the JTT+ Γ 4 model (1113 sites, 108 sequences). Sequences are colored according to their taxonomic classification. Branch statistical supports and duplication events are shown using the same symbols as in Fig. 1. As described in the Material and methods section, we selected all non-mammal species from Ensembl, and kept ten representative mammal organisms and all Ichtyosporea, Choanoflagellida and Metazoa species from our local database

IsoSel: Protein Isoform Selector for phylogenetic reconstructions

<div><p>The reliability of molecular phylogenies is strongly dependent on the quality of the assembled datasets. In the case of eukaryotes, the selection of only one protein isoform per genomic locus is mandatory to avoid biases linked to redundancy. Here, we present IsoSel, a tool devoted to the selection of alternative isoforms in the context of phylogenetic reconstruction. It provides a better alternative to the widely used approach consisting in the selection of the longest isoforms and it performs better than Guidance, its only available counterpart. IsoSel is publicly available at <a href="http://doua.prabi.fr/software/isosel" target="_blank">http://doua.prabi.fr/software/isosel</a>.</p></div