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Ancestral reconstruction reveals mechanisms of ERK regulatory evolution.

ABSTRACT: Protein kinases are crucial to coordinate cellular decisions and therefore their activities are strictly regulated. Previously we used ancestral reconstruction to determine how CMGC group kinase specificity evolved (Howard et al., 2014). In the present study, we reconstructed ancestral kinases to study the evolution of regulation, from the inferred ancestor of CDKs and MAPKs, to modern ERKs. Kinases switched from high to low autophosphorylation activity at the transition to the inferred ancestor of ERKs 1 and 2. Two synergistic amino acid changes were sufficient to induce this change: shortening of the ?3-?C loop and mutation of the gatekeeper residue. Restoring these two mutations to their inferred ancestral state led to a loss of dependence of modern ERKs 1 and 2 on the upstream activating kinase MEK in human cells. Our results shed light on the evolutionary mechanisms that led to the tight regulation of a kinase that is central in development and disease.

SUBMITTER: Sang D

PROVIDER: S-EPMC6692128 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Ancestral reconstruction reveals mechanisms of ERK regulatory evolution.

Sang Dajun D Pinglay Sudarshan S Wiewiora Rafal P RP Selvan Myvizhi E ME Lou Hua Jane HJ Chodera John D JD Turk Benjamin E BE Gümüş Zeynep H ZH Holt Liam J LJ

eLife 20190813

Protein kinases are crucial to coordinate cellular decisions and therefore their activities are strictly regulated. Previously we used ancestral reconstruction to determine how CMGC group kinase specificity evolved (Howard et al., 2014). In the present study, we reconstructed ancestral kinases to study the evolution of regulation, from the inferred ancestor of CDKs and MAPKs, to modern ERKs. Kinases switched from high to low autophosphorylation activity at the transition to the inferred ancestor ...[more]

PMID: 31407663

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Project description:BackgroundThe use of molecular genetic data in phylogenetic systematics has revolutionized this field of research in that several taxonomic groupings defined by traditional taxonomic approaches have been rejected by molecular data. The taxonomic classification of the oribatid mite group Circumdehiscentiae ("Higher Oribatida") is largely based on morphological characters and several different classification schemes, all based upon the validity of diagnostic morphological characters, have been proposed by various authors. The aims of this study were to test the appropriateness of the current taxonomic classification schemes for the Circumdehiscentiae and to trace the evolution of the main diagnostic traits (the four nymphal traits scalps, centrodorsal setae, sclerits and wrinkled cuticle plus octotaxic system and pteromorphs both in adults) on the basis of a molecular phylogenetic hypothesis by means of parsimony, likelihood and Bayesian approaches.ResultsThe molecular phylogeny based on three nuclear markers (28S rDNA, ef-1alpha, hsp82) revealed considerable discrepancies to the traditional classification of the five "circumdehiscent" subdivisions, suggesting paraphyly of the three families Scutoverticidae, Ameronothridae, Cymbaeremaeidae and also of the genus Achipteria. Ancestral state reconstructions of six common diagnostic characters and statistical evaluation of alternative phylogenetic hypotheses also partially rejected the current morphology-based classification and suggested multiple convergent evolution (both gain and loss) of some traits, after a period of rapid cladogenesis, rendering several subgroups paraphyletic.ConclusionsPhylogenetic studies revealed non-monophyly of three families and one genus as a result of a lack of adequate synapomorphic morphological characters, calling for further detailed investigations in a framework of integrative taxonomy. Character histories of six morphological traits indicate that their evolution followed a rather complex pattern of multiple independent gains (and losses). Thus, the observed pattern largely conflicts with current morphological classifications of the Circumdehiscentiae, suggesting that the current taxonomic classification schemes are not appropriate, apart from a recently proposed subdivision into 24 superfamilies.

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Ancestral reconstruction reveals mechanisms of ERK regulatory evolution.

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Ancestral reconstruction reveals mechanisms of ERK regulatory evolution.

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