The first eukaryotic kinome tree illuminates the dynamic history of present-day kinases

Abstract

Eukaryotic Protein Kinases (ePKs) are essential for eukaryotic cell signalling. Several phylogenetic trees of the ePK repertoire of single eukaryotes have been published, including the human kinome tree. However, a eukaryote-wide kinome tree was missing due to the large number of kinases in eukaryotes. Using a pipeline that overcomes this problem, we present here the first eukaryotic kinome tree. The tree reveals that the Last Eukaryotic Common Ancestor (LECA) possessed at least 92 ePKs, much more than previously thought. The retention of these LECA ePKs in present-day species is highly variable. Fourteen human kinases with unresolved placement in the human kinome tree were found to originate from three known ePK superfamilies. Further analysis of ePK superfamilies shows that they exhibit markedly diverse evolutionary dynamics between the LECA and present-day eukaryotes. The eukaryotic kinome tree thus unveils the evolutionary history of ePKs, but the tree also enables the transfer of functional information between related kinases.perspective, there is one substantial hurdle: the large number of kinases in eukaryotes. Only the human kinome tree consists already of 491 ePK domains 7 , and in a collection of nearly 100 eukaryotes, this number increases to over 36,000 ePK domains. Such a number of sequences precludes the use of state-of-the-art alignment as well as tree building software. Moreover, it is a Sisyphean task to analyse a phylogenetic tree that consists of over 36,000 leaves.A more general problem of gene trees is the negative impact of rapidly evolving sequences on statistic support. A commonly used strategy to improve statistic support in species trees is to select slowly evolving genes or positions 17 . For gene trees, an equivalent of this strategy has been proposed: the Scrollsaw method 18 . The Scrollsaw method systematically selects only slowly evolving sequences for generating a gene tree. As a result, both the number of sequences is reduced, and rapidly evolving sequences are excluded. This makes the Scrollsaw method perfectly suitable to handle the large number of ePKs and generate a well-supported eukaryotic kinome tree.Here we present the first eukaryotic kinome tree, generated with a modified and extended version of the Scrollsaw method. The tree reveals ePK superfamily membership for several ePKs that have been labelled as Unaffiliated in the human kinome tree, most notably CAMKK1 and CAMKK2. The tree furthermore unveils that the LECA had much more ePKs than was thought before: at least 92.These 92 ePKs include some surprising examples of ePKs that were previously believed to be specific for certain eukaryotic supergroups, like human CHK1 and the plant CIPKs. The number of LECA ePKs retained in present-day species varies enormously within and between eukaryotic supergroups. The expansion of LECA ePKs since the common ancestor of eukaryotes also differs within and between ePK superfamilies. This variation in LECA ePK dispensability and duplicability is

Timing the origin of eukaryotic cellular complexity with ancient duplications

“…The number of eukaryotic sequences was reduced with a novel method 38 based on the ScrollSaw approach 14 . The idea behind ScrollSaw is that instead of selecting a species subset a priori , the slowest evolving sequences are selected.…”

“…The species in our dataset are from the following six groups: Archaeplastida + Cryptista, SAR + Haptista, Discoba, Metamonada, Obazoa and Amoebozoa. For our main analysis we used BBHs between sequences from two groups, because that provided the best resolution 38 . Although the exact position of the root of the eukaryotic tree of life is uncertain 19 , a likely position is between Opimoda (Obazoa and Amoebozoa in our set) and Diphoda (other supergroups) 18 .…”

Chromosomal instability by mutations in a novel specificity factor of the minor spliceosome

“…First, a phylogenetically diverse set of complete eukaryotic predicted proteomes was utilized. This set was previously compiled to contain the protein sequences of 90 eukaryotic species 43,73 . These species were selected based on their representation of eukaryotic diversity.…”

Kinome-Wide Profiling Identifies Human WNK3 as a Target of Cajanin Stilbene Acid from Cajanus cajan (L.) Millsp.

“…Kinases are essential enzymes for the transmission of information in living organisms. Among the vast majority of kinases, the eukaryotic protein kinase (EPK) family covers one of the biggest superfamilies in the human genome, with a conserved catalytic domain in their structure and fundamental roles in both biological processes and diseases [1,2]. Protein kinases (PKs) transform proteins by phosphorylation, causing a functional alteration of the target protein.…”