Evolution of Bacterial Protein-Tyrosine Kinases and Their Relaxed Specificity Toward Substrates
Artikel i vetenskaplig tidskrift, 2014

It has often been speculated that bacterial protein-tyrosine kinases (BY-kinases) evolve rapidly and maintain relaxed substrate specificity to quickly adopt new substrates when evolutionary pressure in that direction arises. Here, we report a phylogenomic and biochemical analysis of BY-kinases, and their relationship to substrates aimed to validate this hypothesis. Our results suggest that BY-kinases are ubiquitously distributed in bacterial phyla and underwent a complex evolutionary history, affected considerably by gene duplications and horizontal gene transfer events. This is consistent with the fact that the BY-kinase sequences represent a high level of substitution saturation and have a higher evolutionary rate compared with other bacterial genes. On the basis of similarity networks, we could classify BY kinases into three main groups with 14 subgroups. Extensive sequence conservation was observed only around the three canonical Walker motifs, whereas unique signatures proposed the functional speciation and diversification within some subgroups. The relationship between BY-kinases and their substrates was analyzed using a ubiquitous substrate (Ugd) and some Firmicute-specific substrates (YvyG and YjoA) from Bacillus subtilis. No evidence of coevolution between kinases and substrates at the sequence level was found. Seven BY-kinases, including well-characterized and previously uncharacterized ones, were used for experimental studies. Most of the tested kinases were able to phosphorylate substrates from B. subtilis (Ugd, YvyG, and YjoA), despite originating from very distant bacteria. Our results are consistent with the hypothesis that BY-kinases have evolved relaxed substrate specificity and are probably maintained as rapidly evolving platforms for adopting new substrates.

kinase-substrate coevolution


bacterial protein kinases


kinase evolution

kinase classification


Lei Shi

Chalmers, Kemi- och bioteknik, Livsvetenskaper

Boyang Ji

Chalmers, Kemi- och bioteknik, Livsvetenskaper

L. Kolar-Znika

Sveučilište u Zagrebu

INRA Centre de Recherche de Versailles-Grignon

A. Boskovic

INRA Centre de Recherche de Versailles-Grignon

Sveučilište u Zagrebu

F. Jadeau

Université de Lyon

C. Combet

Université de Lyon

C. Grangeasse

Université de Lyon

D. Franjevic

Sveučilište u Zagrebu

E. Talla

Aix-Marseille Université

Ivan Mijakovic

Chalmers, Kemi- och bioteknik, Livsvetenskaper

Genome Biology and Evolution

1759-6653 (ISSN)

Vol. 6 4 800-817


Bioinformatik och systembiologi



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